is there really DMT in salvia? and if so, does anyone know a possibleextraction?
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is there really DMT in salvia? and if so, does anyone know a possibleextraction?
there are many plants that contain DMT as their primary ingredient.....mimosa hostilis being one of them..check erowid..........however a MAOI like syrian rue is used to enhance the experience usually because i think the DMT is in low concentrations
WTF is DMT?
EROWID DOT OH ARE GEE
There are much better things to extract DMT from than salvia, I didn't even know it contained any until I read Dickjustice's post. Kind of worries me, could give them an excuse to ban it. Syrian Rue or some other MAOI is needed only if DMT is taken orally, smoked it's active by itself.
yes, like toads...there is a kind of taod u can get at your local pet store who acualy produces DMT in its glands, and you, YES YOU, can extract it simply, butt im lazy, and dont feel like explaining...google it
I didn't know salvia contained DMT. I'd read quite a bit about it, and I thought the psychoactive component was Salvinorin A? Is DMT actually present?
Here, lemme try and find where I read it. Somewhere on erowid, back in a sec..
Can't find it, so unless I do, assume that info is mistaken. Sorry! My mistake.
Jeez man, I had already started soaking my salvia in methane to extract the dmt... this sucks. So what, is my salvia ruined or something? Damn, that was near a KG too... What a dick...
Kidding. It's cool. Mistakes are made. -laughs- -dances with excitement for his 50mg of 2c-i in the mail- Oh man, my brain and stomach just dances. No one cares, but it danccceesss.
-inhales- No more drinking for encatuse.
I wish to smoke DMT some day. fuck you up.
Fifty miligrams of 2c-i?
Fifty miligrams of 2c-i?!
*bouncy piano vamp, mayor enters stage left*
Say Mayor, have ya heard the news? There's fifty miligrams of 2c-i headed this way! Should be here before the sabbath!
Oh gee, Curly, where'd ya ever glean such glorious information?
I heard it from Black Tar Bart, Mister Mayor! And everyone knows to trust the word of Black Tar Bart!
Well then, Curly, I suppose you'd best help spread the news while I organize a welcome committee!
Gosh mayor, I'm so dog-gone excited I could just... why, I could just...
Yes, Curly, you could just what?
I could just SIIIIIIIIIIIIIIIIIIIIINGGGGGGGGG, OHHHHHH
*mayor and curly in unison*
Yes we're singing
and dancing
and ginger-fairy-prancing
You love me and 2C-I love youuuuu
But before we can trip balls we've got ever so much to do!
*return to vamp, other townsfolk wander in*
Heya Curly! Howdy Mayor Birchum! What's all the hullabaloo?
Oh, hello Cowboy Neal! Why, th' mayor and I were just celebrating on account of the good news!
Aw yeah? What good news is that?
Well, why don'tcha sing along and find out!
We buy it
Supply it
And then we'll 2C-I it!
You eat some I'll eat some more with youuuuuu!
But before we can lose ego we've got oh so much to do!
*other villagers join in elaborately choreographed dance*
Our parents
They told us
That drugs would just unfold us
But what I see tells me that's just not truuuuuuuue
Oh you know that I
(you know that I)
Could tell no lie
(no fucking lie!)
Oh, twooooooo seeeee
EYYYYYEEEEE LOOOOOVVE
YOUUUUUUUUUUUUUUUUUUUUUUUU
*orchestra flourishes*
*curtain*
Wow, spontaneous song and dance, and I though that only happened in the movies.
clap clap clap and so on.
^ by the way i wasn't tryin to be an ass, that really was good =)
Man what the hell was I DOING??
lol, i dunno but it was pretty fuckin funny.
I'm impressed.
wow dick.....
[CONTRIBUTIONS FROM THE CHEMICAL LABORATORY OF THE u. s DEPART-
MENT O F AGRICULTURE, NO. 21 ]
THE CHEIllSTRY OF THE CACTACEAE.??
BS ERVIN E?? EWELL.
Receibed M q 13 1396
I. AN HISTORICAL R E S ~ M E AND PRELIMINARY NOTE.
HERE is probably no more interesting family of plants than T the Cactaceae. This interest is manifest among civilized
and uncivilized peoples, old and young, scientific and unscien-
tific. If there is one that does not feel this interest ; if there is
one that is not inspired with awe at the mere contemplation of
the weird forms assumed by the numerous species of this great
order, which inciudes giants and the tiniest dwarfs : if there is
one that is not moved by the mysterious beauty of an opening
blossom of the ??night-blooming cereus,? then let that one
swallow one or more of the little buttons that we shall exhibit
to you this evening and note whether or not he is susceptible to
the more subtle and more powerful influence that he mill find
working from within. There is scarcely a housewife in the land
that pretends to maintain a conservatory or a window garden
without numbering one or more cacti in her collection. She
would have no hesitation about pronouncing any member of the
order a cactus, so marked are their characteristics ; yet, when it
comes to a more minute study for purposes of classification,
botanists who have spent years in studying them are still dis-
puting about them and have filled the literature of the subject
with a host of synonymous names.
When we examine the chemical side of the subject, we find
that our knowledge is still more imperfect. The fact that many
of these plants are used for food and that their juices are drunk
in place of water by the travellers in the arid regions where they
grow in abundance, has caused them to be regarded as devoid
of chemical constituents of greater importance than those that
are to be expected in any of the innocent plants of humid
regions. Various species have been used medicinally in the
countries in which they grow. Cerezis grandifiorzcs and a few
allied species have attained a reputatioii in medical practice
1 An abstract of this paper was read before the Washingtou Sectiou of the American
Chemical Society, Apn19 1896
CHEMISTRY OF THE CACTACEAE. 625
among peoples more advanced in the scale of civilization, and
have consequently been made the subject of some chemical
investigation. Their fresh juices produce irritation of the skin
when locally applied, and preparations of them are administered
internally as cardiac stimulants and for other purposes. The
first article published in this country on the subject seems to
have been one by A. F. Pattee, which appeared in the Boston
Medical and Surgical journal in 1867. 0. M. Meyers published
an article in the New York Medical journal in 1891, in which he
called attention to the value as a heart tonic of a preparation of
Cereus grandiforris called ?? ?? cactina. ? This was claimed to be
the active principle of the drug, but it was not stated whether it
was alkaloidal, glucosidal, or of some other nature. Numerous
papers quickly followed, containing reports of clinical experi-
ments with this and other preparations of the drug. Some of
these papers included brief reports of chemical investigations.
Boinet and Boy-Tessier reported the finding of an alkaloid in
this species.?? G. Sharp?? stated that he was unable to find
either alkaloid or glucoside in the drug, and ascribed any active
properties that it may have to the resin that it contains. He
failed to obtain any marked effect from the drug itself, and
took doses of forty and one hundred of the cactus pills, pre-
pared from CactusMexicana, without result. Thisis practically all
that has been done in the way of chemical investigation of this
class of plants in recent years, excepting the species that we are
to consider and a few species closely related thereto.
As far as I have been able to learn, three groups of persons
have been especially active in the scientific study of the Cac-
taceae during the last decade : First, a group of persons at Ber-
lin, the center of which is Dr. L. Lewin, whose earlier work has
been reported in this country in a pamphlet published by Parke,
Davis & Co., of Detroit, and in the Therapeutic Gazette for 1888 ;
second, a group of persons at the Pharmacological Institute of
the University of Leipsic, where the work has been conducted
by Dr. Arthur Heffter ; third, a group of persons in this city,
centering in the Bureau of American Ethnology, and including
1 Bulletin &&a1 de Thevupeutique, 1891, 121, 343-349.
2 London Praclifionw, 1894.
626 ERVIN E. EWELI,.
as associates the Division of Chemistry of the Department of
Agriculture for chemical studies, Drs. Prentiss and Morgan for
the study of physiological properties, and the Botanical Division
of the Department of Agriculture for the settlement of botanical
questions. These more recent investigations have been directed
toward one or more species of cacti that are used by the hmeri-
can Indians for ceremonial and medicinal purposes. This sub-
stance, known as ??mescal buttons ? in the commerce of our
southwestern border and in Mexico as peyote or pelZoole, has been
of commercial and medicinal importance in Mexico for many
years, being mentioned by Spanish writers as early as 1790. It
was included in the Mexican Pharmacopoeia of 1842, but has
been omitted from the later editions. The species furnishing
the ?? ( mescal buttons ? is Anhalonium Lez~hii (Hennings) , for
which the synonymous names are .4nhaloniicm Williamsii, var. ,
Lewiniiand Lophophora WiZliamsii, var., Leadnii. There seems to
be evidence that Anhalonium Williamsii also contributes to the
supply of This latter species is
likewise burdened with an abundance of names, being known
among botanists by the names of Echizocactus Willianzsii and
Lopho@hora WilZiamsii, in addition to the one just used to des-
ignate it.
buttons ? by
the Indians, I quote, by permission, from a recent article on the
subject by hIr. James Mooney of the Bureau of American
Ethnology :
??About five years ago, while making investigations among
the Kiowa Indians on behalf of the Bureau of Ethnology, the
attention of the writer was directed to the ceremonial use of a
plant for which were claimed wonderful medical and psychologic
properties. So numerous and important are its medical applica-
tions, and so exhilarating and glorious its effect, according to
the statements of the natives, that it is regarded as the vegetable
incarnation of a deity, and the ceremonial eating of the plant
has become the great religious rite of all the tribes of the south-
ern plains. +
mescal buttons ? and pellote.
For a detailed account of the use of the dried
# # # # + + * +
Thevapeutrc Gazefte, Jauii. 1 The Mescal Plant and Ceremony. by James Mooney.
ary, 1896
CHEMISTRY OF THE CACTACEAE. 627
??As a matter of fact, there are several varieties, probably all
of the same genus, used by the Indians in a ceremonial way.
The explorer Lumholtz mentions three varieties among the
Tarahumari of northern Mexico, (see his article in Scm??bner??s
Magazine for October, 1894). A different sort, from the lower
Rio Grande, is used by the Kiowas and associated tribes, and
a smaller variety is found among the Mescalero Apaches of
eastern New Mexico. In each language it has a different name,
usually referring to the prickles. Among the Kiowas it was
se6i; among the Comanches, wokowi ; with the Mescaleros, ho ;
and with the Tarahumaris, hikori. The traders of the Indian
Territory commonly call it mescal, although it must not be con-
founded with another mescal in Arizona, the Agave, from
which the Apaches prepare an intoxicating drink. The local
Mexican name upon the Rio Grande is peyote or peZlote, from
the old Aztec name peyotl.
?? The use of the plant for medical and religious purposes is
probably as ancient as the Indian occupancy of the region over
which it grows. There is evidence that the ceremonial rite was
known to all the tribes from the Arkansas to the valley of
Mexico, and from the Sierra Madre to the coast. The Mesca-
lero Apaches take their name from it. Personal inquiry among
the Navajos and Mokis proved that they had no knowledge
of it.
I ?? In proportion as the plant was held sacred by the Indians,
so it was regarded by the early missionaries as the direct inven-
tion of the devil, and the eating of the peyote was made a crime
equal in enormity to the eating of human flesh. From the
beginning it has been condemned without investigation, and
even under the present system severe penalties have been
threatened and inflicted against Indians using it or having it
in their possession. Notwithstanding this, practically all the
men of the Southern Plains tribes eat it habitually in the cere-
mony, and find no difficulty in procuring all they can pay for.
In spite of its universal use and the constant assertion of the
Indians that the plant is a valuable medicine and the ceremony
a beautiful religious rite, no agency physician, post surgeon,
628 ERVIN E. EWELL.
missionary, or teacher-with a single exception-has ever tested
the plant or witnessed the ceremony.
??A detailed account of mythology, history and sacred ritual
in connection with the mescal would fill a volume. Such an
account, to be published eventually by the Bureau of Ethnology,
the writer is now preparing, as the result of several years of
field study among the Southern Plains tribes.
???? The ceremony occupies from twelve to fourteen hours,
beginning about nine or ten o??clock and lasting sometimes until
nearly noon the next day. Saturday night is now the time
usually selected, in deference to the white man??s idea of Sunday
as a sacred day and a day of rest. The worshippers sit in a
circle around the inside of the sacred tipi, with a fire blazing in
the center. The exercises open with a prayer by the leader,
who then hands each man four mescals, which he takes and eats
in quick succession, first plucking out the small tufts of down
from the center. In eating, the dry mescal is first chewed in
the mouth, then rolled into a large pellet between the hands,
and swallowed, the man rubbing his breast and the back of his
neck at the same time to aid the descent. After the first round
the leader takes the rattle, while his assistants take the drum,
and together they sing the first song four times, with full voices,
at the same time beating the drum and shaking the rattle with
all the strength of their arms. The drum and rattle are then
handed to the next couple, and so the song goes on rouud and
round the circle-with only a break for the baptismal ceremony
at midnight, and another for the daylight ceremony-until per-
haps nine o??clock the next morning. Then the instruments are
passed out of the tipi, the sacred foods are eaten, and the cere-
mony is at an end. At midnight a vessel of water is passed
around, and each takes a drink and sprinkles a few drops upon
his head. Up to this hour no one has moved from his position,
sitting cross-legged upon the ground and with no support for
his back, but now any one is at liberty to go out and walk about
for a while and return again. Few, howover, do this, as it is
considered a sign of weakness. The sacred food at the close
of the ceremony consists of parched corn in sweetened water ;
rice or other boiled grain ; boiled fruit, usually now prunes or
CHEMISTRY OF THE CACTACEAE. 629
dried apples ; and dried meat pounded up with sugar. Every
person takes a little of each, first taking a drink of water toclear
his mouth.
??After midnight the leader passes the mescal around again,
giving to each man as many as he may call for. On this second
round I have frequently seen a man call for ten and eat them one
after the other as rapidly as he could chew. They continue to
eat at intervals until the close. There is much spitting, and
probably but little of the juice is swallowed. Every one smokes
hand-made cigarettes, the smoke being regarded as a sacred
incense. At intervals some fervent devotee will break out into
an earnest prayer, stretching his hands out toward the fire and
the sacred mescal the while. For the rest of the time, when not
singing the song and handling the drum or rattle with all his
strength, he sits quietly with his blanket drawn about him and
his eyes fixed upon the sacred mescal in the center, or perhaps
with his eyes shut and apparently dozing. Hemust be instantly
ready, however, when his turn comes at the song, or to make a
prayer at the request of some one present, so that it is apparent
that the senses are always on the alert and under control of the
will.
?? There is no preliminary preparation, such as by fasting or
the sweat-bath, and supper is eaten as usual before going in.
The dinner, which is given an hour or tw*o after the ceremony,
is always as elaborate a feast as the host can provide. Therest
of the day is spent in gossiping, smoking, and singing the new
songs, until it is time to return home. They go to bed at the
usual time, and are generally up at the usual time the next
morning. No salt is used in the food until the day after the
ceremony.
??As a rule, only men take part in the regular ceremony, but
sick women and children are brought in, and, after prayers for
their recovery, are allowed to eat one or more mescals prepared
for them by the priest.?
I t is to Mr. Mooney that we are indebted for the commence-
ment of the scientific study of the drug in this country. On his
return in the summer of 1894, from a prolonged residence among
the tribes that use the drug, he brought with him a considerable
630 ERVIN E. EWELL.
quantity of the dried buttons? for use in scientific investiga-
tions. A portion of this material was turned over to Dr. H . U??.
Wiley, Chief of the Division of Chemistry of the Department of
Agriculture, for a study of its chemical constituents. This task
was assigned to the author by Dr. Wiley in September, 1894.
The only literature of the subject at hand at that time was the
article published by Dr. Lewin in 1888,?? in which he announced
the discovery and name, anhalonin, of an alkaloid in Ax-
haZonium Lewinii, a name that had been given to the plant
furnishing ??mescal buttons I ?? by Hennings, the botanist to
whom Lewin intrusted the botanical identification of the crude
material in which the alkaloid was found. Work had hardly
been begun in the laboratory of the Department of Agriculture
with the result of the separation of a considerable portion of
Lewin??s anhalonin, when Dr. Heffter2 published an article in
which he reported the results of a chemical study of four species
of the genus Anhalonium : A. fissurafuiii, A. jrismaticum, A.
WiZZiamsii, A . Lewinii. This was quickly followed by a report
by Lewin of the continuation of his experiments mentioned
above. a
For the aid of the American readers who may feel an interest
in this subject, the writer has prepared the following table, in
which the results of the investigations, hitherto reported, of the
three more thoroughly studied species of anhalonium, are pre-
sented in a convenient form for reference and coniparison :
1 Archiv fiir ex&&menielle Pathologie utid Pharmakoiogie, 1888, 14, 401 ; Thwapeutrc
Gazette. 1888, p. 232, and in a pamphlet issued by Parke, Davis 8; Co.. of Detroit. the
same being a reprint from ?? The Pharmacology of the Newer Materia Medica.?
2 .4rchiv fi2v expperimentelle Pathologie tend Pharmakologre. 1894, 34, 65-56.
8 Avchivfiir experimentelle Pathologif aird Phavmakologie. 1894. 34, 374-391
ERVIS E. EWELL.
CHEMISTRY OF THE CACTACEAE. 633
d w Y
1 c) .I .I .* .-
a
a
v
a
u
6 t!
k
634 ERVIX E. EWELL.
CHEMISTRY OF T H E CACTACEAE. 635
V
636 ERVIN E. EWELL.
CHEMISTRY OF THE CACTACEAE. 637
63 8 ERVIN E. EWELL.
All of the bases mentioned in the above table are possessed of
marked physiological properties, and produce death when
administered to the lower animals in sufficient doses. The
nature and extent of the physiological activity of these alkaloids
as determined by the experiments of Lewin and Heffter, are
shown in the following table :
640 ERVIN E . EWELL.
L
CHEMISTRY OF THE CACTACEAE. 64 1
The materials used by Lewin in his experiments reported in
1894 were prepared in the laboratory of E. Merck & Co., of
Darmstadt. I n their report to Lewin, mention was made of the
presence of still a third base in the drug, which forms a crystal-
lizable hydrochlorate that is easily soluble in cold water. It
seems quite possible that the substance described under the
name of amorphous anhalonin hydrochlorate? was a mixture
of alkaloidal hydrochlorates.
Heffter also made a cursory examination of a small sample of
A~~~aZoniumprismaticum and found it to contain a sniall per-
centage of alkaloidal constituents possessing high physiological
activity.
In the article published by Lewin, in 1894, and cited above,
mention is made of a partial analysis of a sample of Anhalonium
Jourdanianum made in 1889 with the result of the separation of
an alkaloid that formed a crystalline hydrochlorate and resem-
bled anhalonin in its characteristic color-reaction as well as the
nature of its physiological action upon frogs. In the same ar-
ticle report is also made of an examination of Anhalonium
WiZZiamsii, several species of Mammillaria, and one species of
Opuntia. The study of A . WiZZiamsii, which was made in 1891,
resulted in the separation of an alkaloid that caused an increase
of reflex excitability, and marked tetanus when administered to
frogs. The tendency of the tetanic condition to continue for
several days was very pronounced. The milky juices yielded
by MamijZaria polythele, M. centn??nrrha var. PachytheZe, M. juZ-
chra, Haw. rcnd M. arietina, were found to possess no poisonous
properties. Mammillaria uberiformis was found to be poison-
ous. RhipsaZis conferta, a member of the Opuntia group, yielded
a slimy juice that was difficultly soluble in water. When this
was administered to frogs by hypodermic injection a paralysis
of the voluntary muscles was produced, which was followed by
heart failure.
It is very apparent from the results of the investigations
which I have thus briefly summarized, that the Cactaceae is a
group of plants worthy the attention of the botanist, the chem-
ist, the pharmacologist, the physician, and the toxicologist, as
well as the attention of the entire mass of nature-loving human-
642 CHEMISTRT O F THE C.\C??l??XCEAE.
ity. It is to be hoped that American scientistswill not leave the
task of exploring this promising field entirely to workers beyond
the sea, considering our proximity to much of the necessary
material.
I t is the purpose of the present article to bring the subject to
the attention of American investigators and to briefly outline
the work that has been done in :he laboratory of the U. S.
Department of Agriculture. Mescal buttons,? thedried, com-
mercial form of Anhaloizium Lewinii, have served as the start-
ing point for all our investigations. Fig. I shows the appear-
ance of the ?? ?? buttons? when viewed upon the top, upon the
edge, and upon the under side.
Figs. 2 , 3, 4, and 5, show the appearance of living specimens
of Ayzhalonium Lewizii, A. Williamsii, A. &miraturn, and A .
prismaticurn, respectively, the illustrations being prepared from
photographs made by the author from plants growing in the
National Botanical Gardens.
An alkaloid corresponding in its properties to Lewin??s anha-
lonin has been prepared in a considerable amount and in a high
state of purity. Fig. 6 shows the appearance of the bottom of a
crystallizing dish in which the hydrochlorate was crystallized
from alcohol by spontaneous evaporation over sulphuric acid in
a vacuum.
A second and, very recently, a third alkaloid have been sepa-
rated from the drug. All three of these alkaloidal preparations
have been subjected to physiological tests by Drs. Prentiss and
Morgan, and the results of their investigations will soon be pub-
lished in the Medical Record. They have recently published
two articles upon the physiological action and therapeutic value
of the crude drug in the Therapeutic Gazette.?? As for the third
alkaloid separated, let it suffice to say for the present that it has
been found to be much stronger than any alkaloid hitherto sepa-
rated froni any member of the genus Anhalonium, as 0.02-0.025
gram of its hydrochlorate per kilo or body weight is fatal to rab-
bits, and 0.03 gram per kilo of body weight suffices to kill a full
grown guinea-pig. The hydrochlorate of this alkaloid crystal-
lizes in nodular groups of radiating needles. Fig. 7 was made
1 Sept.. 789j, and Jan , r896.
REFINING LIXIVIATION SULPHIDES. 643
from a photograph of crystals obtained by the spontaneous
evaporation of a solution of the alkaloidal salt in ninety per cent.
alcohol.
An examination of the resinous constituents of the plant is in
progress, as well as a study of those of its constituents that are
of interest to the vegetable physiologist rather than to the
therapeutist.
A more extended report 6f this work is reserved for a future
paper. Before closing this preliminary announcement, how-
ever, I wish to express my indebtedness to Dr. Wiley for much
greatly appreciated assistance in the work, and to Dr. Brown for
the aid that he very kindly rendered me in the preparation of
the photographs used for the illustration of the article. I also
desire to express my appreciation of the patience with which
both Dr. Wiley and the gentlemen of the Bureau of Ethnology
have awaited the progress of this work, which has been
largely limited to spare moments not required by other duties.
WASHINGTON, D. C., May 11, 1896.
THE SULPHURIC ACID PROCESS OF REFINING LIXIVI-
ATION SULPHIDES.'
BY FREDERIC P. DEWEY,
Received May 91, 1896.
HE time is fast approaching when more chemistry must be T used in the extraction of the preciousmetalsin the United
States. The chief objections to chemical methods are the tech-
nical skill required in the management, the higher grade of labor
necessary and the time required to turn out product, thus lock-
ing up large amounts of capital ; but these difficulties are becom-
ing less applicable all the time. Then too, the wonderful suc-
cess attained in this country in extracting the precious metals
by smelting with lead has retarded the application of chemical
met hods.
The chemical process of extracting silver by lixiviating, or
leaching its ores with solution of hyposulphite of sodium, was
introduced by von Patera in 1858, and has been variously
improved, notably by the substitution of the calcium salt for
Read before the Washington Section of the American Chemical Society, March xz,
1896.
Salvinorin C, a New Neoclerodane
Diterpene from a Bioactive Fraction of
the Hallucinogenic Mexican Mint Salvia
divinorum
Leander J. Valde´s III,*,?* Hui-Ming Chang,? Daniel C. Visger,§ and
Masato Koreeda*,§,^
UniVersity of Michigan Hospital, Pharmacy SerVices, Ann Arbor, Michigan 48109,
School of Pharmacy, Northeast Louisiana UniVersity, Monroe, Louisiana 71209,
and Departments of Chemistry and Medicinal Chemistry, UniVersity of Michigan,
Ann Arbor, Michigan 48109
[email protected]
Received September 26, 2001
ABSTRACT
Salvinorin C (1), a minor component from a biologically active TLC fraction, was isolated from the leaves of the Mexican mint Salvia divinorum.
Its structure was elucidated on the basis of extensive proton and C-13 NMR experiments, as well as by comparison of the NMR data with
those of the mono- and diacetate derivatives 5-7 of the major NaBH4-reduction product of salvinorin A (2).
As part of our continuing investigations1-6 of the psychotropic
Mexican labiate SalVia diVinorum (Epling & Jativa´-
M.), we report the isolation and structure of a new transneoclerodane
diterpene, salvinorin C (1). Previous studies
of the mint led to the isolation of salvinorins (divinorins) A
(2) and B (3),2,7 as well as the unambiguous determination
of their absolute stereochemistry6 by the use of the exciton
chirality circular dichroism method.8 Salvinorin A exhibits
activity paralleling that of mescaline, the prototype hallucinogen,
in the modified open field bioassay.2,5,9 Research
in humans has shown that, although essentially inactive when
taken orally, vaporizing and inhaling 200-500 ?g of
salvinorin A induces profound hallucinations.10 Salvinorin
A is the first diterpene to be identified as a hallucinogen in
humans and is one of the most potent naturally occurring
compounds thus far isolated.11 We have discussed the effects
of S. diVinorum and salvinorin A in animals and humans
?* University of Michigan Hospital.
? Northeast Louisiana University.
§ Department of Chemistry, University of Michigan.
^ Department of Medicinal Chemistry, University of Michigan.
(1) Valde´s, L. J., III; Dı´az, J. L.; Paul, A. G. J. Ethnopharmacol. 1983,
27, 287-312.
(2) Valde´s, L. J., III; Butler, W. M.; Hatfield, G. M.; Paul, A. G.;
Koreeda, M. J. Org. Chem. 1984, 49, 4716-4720.
(3) Valde´s, L. J., III. J. Nat. Prod. 1986, 49, 171.
(4) Valde´s, L. J., III; Hatfield, G. M.; Koreeda, M.; Paul, A. G. Econ.
Bot. 1987, 41, 283-291.
(5) Valde´s, L. J., III. J. PsychoactiVe Drugs 1994, 26, 277-283.
(6) Koreeda, M.; Brown, L.; Valdes, L. J., III. Chem Lett. 1990, 2015-
2018.
(7) Ortega, A.; Blount, J. F.; Marchand, P. S. J. Chem. Soc., Perkin Trans.
1 1982, 2505-2508.
(8) Harada, N.; Nakanishi, K. Circular Dichroic Spectroscopy-Exciton
Coupling in Organic Stereochemistry; University Science Books: Mill
Valley, CA, 1983.
(9) Valde´s, L. J., III. Ph.D. Dissertation, University of Michigan, Ann
Arbor, Michigan, 1983. See also: Brimblecombe, R. W.; Green, A. L.
Nature (London) 1962, 45, 983.
(10) Siebert, D. J. J. Ethnopharmacol. 1994, 43, 53-56.
(11) Schultes, R. E.; Hofmann, A. The Botany and Chemistry of
Hallucinogens; Charles, C., Ed.; Thomas Publisher: Springfield, IL, 1980.
ORGANIC
LETTERS
2001
Vol. 3, No. 24
3935-3937
10.1021/ol016820d CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/03/2001
and warned of their potential to become drugs of abuse.5
During our research on S. diVinorum, salvinorin A was first
isolated from a single pharmacologically active TLC band
using a solvent system of 100/10/1 CHCl3/MeOH/H2O.
Differences in potency between the purified diterpene and
the original TLC fraction led us to surmise that the latter
contained other strongly bioactive compounds that cochromatographed
with salvinorin A during the chromatographic
separation. Upon changing the solvent system to 1/1
hexanes/EtOAc, the minor component became separated
from salvinorin A. Even though it is estimated that salvinorin
C comprises only about 10% of the pharmacologically active
TLC fraction, the rest being salvinorin A, the fraction was
significantly more potent than an equivalent amount of
salvinorin A alone. This seems to indicate that the new
diterpene may also have strong psychotropic activity.
Air-dried, pulverized leaves (0.49 kg) of S. diVinorum were
extracted as before2 with ether, and salvinorins were isolated
by repeated flash column chromatography. Final purification
of salvinorin C was achieved by HPLC.12 Repeated recrystallization
from hexanes/EtOAc provided pure salvinorin C
(1)13 (38.5 mg): mp 196-198 °C, [R]22
D +49.3 (c 0.61,
CHCl3).
Salvinorin C (1) has the molecular formula C25H30O9, and
its IR spectrum suggests the presence of an R,??-unsaturated
ester (1715 cm-1), as well as another ester and a ?-lactone
(1755 and 1735 cm-1, respectively). Its complete structure
was elucidated by the use of 1H and 13C NMR spectroscopy.
NMR data were compared with those of salvinorin A (2)
and the acetate derivatives of the major product obtained by
the NaBH4-reduction of salvinorin A. Partial structures
deduced by the analysis of NMR data are indicated in
connecting thick lines (Figure 1). Although no splitting was
visible between H-1 and H-10 in the 1H NMR spectrum of
salvinorin C (J1,10 < 0.8 Hz), irradiation of the H-1 peaks
sharpened the H-10 singlet. In addition, at the same time
the H-3 peaks collapsed into a doublet, confirming the
presence of the W-shape coupling between H-1 and H-3 (J
) 1.4 Hz). The connectivity between the C-12 and the furan
group was established by the detection of the weak coupling
between H-12 and H-16 (4J12,16 ) 0.8 Hz).
In an effort to further ascertain the structure of salvinorin
C, salvinorin A (2) was reduced with NaBH4 in isopropyl
alcohol (35 °C, 2.5 h). As we reported earlier,2 the reaction
produced a 2.3:1 mixture of cis-diol 4 and its C-8 epimer14
in 87% combined yield. Attempts at directly forming the
1,2-diacetate from diol 4 proved virtually impossible with
Ac2O/pyridine, even at elevated temperatures, presumably
as a result of the severe steric hindrance of the 1R-OH
imposed by the two 1,3-diaxially juxtaposed methyl groups.
Instead, the formation of 2-monoacetate 62 was observed.
Therefore, in analogy to a similar situation encountered in
our study on forskolin,15 diol 4 was first treated with trimethyl
orthoacetate at 100 °C in the presence of a catalytic amount
of acetic acid. Immediate acid-catalyzed hydrolysis of the
resulting 1,2-cyclic orthoacetate provided 1-monoaceate 516
in 83% yield, consistent with the general observation on the
selective formation of the axial monoester of diols obtainable
upon acid hydrolysis of their cyclic ortho ester derivatives.17
Acetylation of 5 under standard conditions then afforded the
desired 1,2-diacetate 718 in 94% yield.
Comparison of the 13C NMR chemical shifts of salvinorin
C (1), monoacetates 5 and 6, and diacetate 7 (Table 1) gave
(12) A 10-?m Radial Pak Microporasil silica gel column (10 cm 8
mm id) eluted with an isocratic solvent mixture of 10% acetonitrile, 30%
methyl-tert-butyl ether, and 60% hexanes with a flow rate of 1.5 mL/min.
(13) Salvinorin C (1): IR (KBr) 3150, 2950, 2920, 2850, 1755, 1735,
1715, 1635, 1430, 1370, 1310, 1225, 1140, 1070, 1035, 955, 905, 870,
785, 765 cm-1; HRMS (EI) m/z calcd for C25H30O9 474.1890, found
474.1865.
(14) Data for the 8-epimer of diol 4: mp 234-235 °C (EtOH); [R]22
D
+8.8 (c 0.24, MeOH); 1H NMR (400 MHz, acetone-d6) ? 0.97 (d, 1H, J
) 1.1 Hz), 1.33 (s, 3H), 1.43 (ddd, 1H, J ) 13.7, 4.5, 3.9 Hz), 1.60 (ddd,
1H, J ) 13.7, 13.6, 5.0 Hz), 1.58-1.68 (m, 1H), 1.70 (s, 3H), 1.82 (dd,
1H, J ) 12.1, 11.6 Hz), 1.91 (dddd, 1H, J ) 13.6, 13.3, 4.7, 3.9 Hz), 2.03
(dddd, 1H, J ) 13.3, 5.0, 4.5, 1.9 Hz), 2.14 (dd, 1H, J ) 11.6, 1.9 Hz),
2.16 (dd, 1H, J ) 9.7, 1.9 Hz), 2.17 (ddd, 1H, J ) 12.0, 11.5, 9.7 Hz),
2.60 (dd, 1H, J ) 4.7, 1.9 Hz), 2.86 (s, 1H, 1-OH), 2.89 (s, 1H, 2-OH),
3.60 (ddd, 1H, J ) 11.5, 4.5, 2.3 Hz), 3.62 (s, 3H), 4.09 (dd, 1H, J ) 2.3,
1.1 Hz), 5.49 (ddd, 1H, J ) 12.1, 1.9, 1.2 Hz), 6.58 (dd, 1H, J ) 1.8, 0.7
Hz), 7.57 (dd, 1H, J ) 1.8, 1.7 Hz), 7.66 (ddd, 1H, J ) 1.7, 1.2, 0.7 Hz);
13C NMR (75 MHz, acetone-d6) ? 17.36 (q), 18.91 (t), 26.59 (q), 29.77 (t),
37.43 (s), 37.51 (s), 37.85 (t), 46.85 (d), 49.67 (t), 51.15 (q), 55.38 (d),
55.48 (d), 70.08 (d), 70.21 (d), 71.93 (d), 109.66 (d), 125.90 (s), 140.80
(s), 144.38 (d), 173.75 (s), 174.31 (s). Anal. Calcd for C21H28O7: C, 64.60;
H, 7.23. Found: C, 64.14; H, 7.18.
(15) Valdes, L. J., III.; Koreeda, M. J. Org. Chem. 1991, 56, 844-846.
Figure 1. Partial structures and their connectivity (bold lines)
established by 1H and 13C NMR spectroscopy.
3936 Org. Lett., Vol. 3, No. 24, 2001
further credence to the proposed structure of salvinorin C.
In addition, examination of the 1H NMR spectra of salvinorin
C (1) and diacetate 7 was informative in deducing the A-ring
stereochemistry of both compounds. A long-range W-type
coupling (1.2 Hz) was observed between the two equatorial
Hs at C-1 and C-3 in diacetate 7 as in the case of salvinorin
C (vide ante).
These salvinorin compounds from S. diVinorum closely
resemble a large number of neoclerodane diterpenes isolated
from Latin American SalVia plants.19 It would be interesting
to examine if any of those compounds also exhibit psychotropic
activity.
Acknowledgment. This work was supported in part by
research grants from the NIH (to M.K.) and the University
of Michigan College of Pharmacy (to L.J.V.).
OL016820D
(16) Data for 5: mp 206-209 °C (hexanes/EtOAc); [R]22
D +7.1 (c 0.70,
CHCl3); 1H NMR (400 MHz, CDCl3) ? 1.16 (s, 3H), 1.36 (s, 3H), 1.42
(ddd, 1H, J ) 13.9, 13.0, 3.6 Hz), 1.47 (d, 1H, J ) 1.7 Hz), 1.60 (dddd,
1H, J ) 14.1, 13.9, 12.1, 2.9 Hz), 1.62 (d, 1H, J ) 1.7 Hz), 1.72 (ddd, 1H,
J ) 13.0, 3.5, 2.9 Hz), 1.73 (dddd, 1H, J ) 13.0, 4.9, 2.8, 1.0 Hz), 1.90
(dd, 1H, J ) 13.2, 11.7 Hz), 2.00 (dddd, 1H, J ) 14.1, 3.6, 3.5, 3.2 Hz),
2.07 (s, 3H), 2.11 (ddd, 1H, J ) 13.2, 13.0, 12.1 Hz), 2.32 (dd, 1H, J )
13.2, 2.8 Hz), 2.35 (dd, 1H, J ) 12.1, 3.2 Hz), 2.48 (dd, 1H, J ) 13.2, 5.4
Hz), 3.64 (s, 1H, OH), 3.65 (s, 3H), 3.68 (ddd, 1H, J ) 12.1, 4.9, 1.7 Hz),
5.54 (dd, 1H, J ) 11.7, 5.4 Hz), 5.60 (ddd, 1H, J ) 1.7, 1.7, 1.0 Hz), 6.59
(dd, 1H, J ) 1.8, 0.8 Hz), 7.57 (dd, 1H, J ) 1.8, 1.5 Hz), 7.68 (ddd, 1H,
J ) 1.5, 0.8, 0.8 Hz). Anal. Calcd for C23H30O8: C, 63.58; H, 6.96.
Found: C, 63.42; H, 7.00.
(17) King, J. F.; Allbutt, A. D. Can. J. Chem. 1970, 48, 1754-1769.
(18) Data for 7: mp 211-214 °C (hexanes/EtOAc); [R]22
D -7.5 (c 0.81,
CHCl3); 1H NMR (400 MHz, acetone-d6) ? 1.16 (s, 3H), 1.38 (s, 3H), 1.50
(dddd, 1H, J ) 14.0, 12.8, 12.2, 2.6 Hz), 1.62 (d, 1H, J ) 1.7 Hz), 1.63
(ddd, 1H, J ) 13.0, 12.8, 3.2 Hz), 1.76 (dddd, 1H, J ) 12.9, 4.8, 2.8, 1.2
Hz), 1.78 (ddd, 1H, J ) 13.0, 3.2, 3.0 Hz), 1.90 (s, 3H), 1.94 (dd, 1H, J )
13.2, 11.7 Hz), 2.02 (dddd, 1H, J ) 14.0, 3.3, 3.2, 3.0 Hz), 2.14 (s, 3H),
2.23 (ddd, 1H, J ) 13.2, 12.9, 12.4 Hz), 2.32 (dd, 1H, J ) 13.2, 5.5 Hz),
2.40 (dd, 1H, J ) 12.2, 3.3 Hz), 2.45 (dd, 1H, J ) 13.2, 2.8 Hz), 3.67 (s,
3H), 4.81 (ddd, 1H, J ) 12.4, 4.8, 3.4 Hz), 5.56 (dd, 1H, J ) 11.7, 5.5
Hz), 5.68 (ddd, 1H, J ) 3.4, 1.7, 1.2 Hz), 6.58 (dd, 1H, J ) 1.8, 0.8 Hz),
7.56 (dd, 1H, J ) 1.8, 1.5 Hz), 7.66 (ddd, 1H, J ) 1.5, 0.8, 0.8 Hz). Anal.
Calcd for C25H32O9: C, 63.01; H, 6.77. Found: C, 62.87; H, 6.71.
(19) Rodriguez-Hahn, L.; Alvarado, G.; Ca´rdenas, J.; Esquivel, B.;
Gavin?o, R. Phytochemistry 1994, 35, 447-450 and references therein.
Table 1. NMR Data for 1 and 5-7 in CDCl3
a
salvinorin C (1)
?¸ ?C
1-OAc
5 ?C
2-OAc
6 ?C
diacetate
7 ?C
Divinorin A, a Psychotropic Terpenoid, and
Divinorin B f r o m the Hallucinogenic Mexican
Mint Salvia divinorum
Leander J. Valdes, III,*t William M. Butler,'
George M. Hatfield,' Ara G. Paul,' and Masato Koreeda**J
School of Pharmacy and Department of Chemistry, The
University of Michigan, Ann Arbor, Michigan 48109
Received January 31, 1983
While nonalkaloidal constituents have been implicated
as being at least partially responsible for the biological
School of Pharmacy.
t Department of Chemistry.
0022-326318411949-4716$01.50/0
activity of several hallucinogenic plants,2 little has been
reported on the structures of such possible hallucinogens.
The Mexican labiate Salvia divinorum (Epling and Jati-
va-M.) is used in divinatory rites by the Mazatec Indians
of Oaxaca, Mexico. An infusion prepared from the crushed
fresh leaves of this plant (known locally as sku Maria
Pastora) is used to induce "visions" and its psychotropic
effects have been verified by a number of researcher^.^
(1) Address correspondence to this author at the Department of
Chemistry.
(2) (a) Shultes, R. E.; Hofmann, A. "The Botany and Chemistry of
Hallucinogens"; Charles C. Thomas Publisher: Springfbld, IL, 1980; !2nd
ed. (b) Lewis, W. H.; Elvin-Lewis, M. P. F. In 'Medical Botany"; Wiley:
New York, 1977; Chapter 18. (c) Dim, J. L. Ann. Reu. Pharmacol.
Toxicol. 1977, 17, 647.
0 1984 American Chemical Society
Notes
(A) 6375 7.389
(dd, 092, 1.83) (dd, l.53.183)
- 2
I Y?.?.
J. Org. Chem., Vol. 49, No. 24, 1984 4717
(B)
C H j
20.53
'171.57
Figure 1. Divinorin A (1): (A) 360-MHz 'H NMR data in CDCl,, 6 values from (CHdSi [multiplicity and J values (in Hz) in parentheses];
(B) 90.56-MHz 13C NMR data in CDC13, S values from (CH3),S1; assignments are based on off-resonance, selective, and gated-selective
decoupling experiments and chemical shift comparisons with compounds 2-4 and model compounds.
Furthermore, upon administration of large doses of the
plant extract in animals, one observes behavioral patterns
that resemble the "intoxication" the infusion produces in
human beings. Despite previous investigations, the prin-
ciple(s) responsible for this biological activity has never
been identified.4 We now report the isolation and the
structures of the new neoclerodane diterpenes, divinorins
A and B from S. divinorum. Divinorin A, the first clearly
documented psychotropic terpenoid: exerts a sedative
effect on mice when tested in a bioassay based on a
modification of Hall's open field.6
Lyophilized, pulverized leaves (5.35 kg) of S. divinorum
were extracted with ether. The nonpolar components were
removed from the concentrated extract through partition
between hexanes and 90% aqueous methanol. The dried
methanolic fraction was crudely purified by silica gel flash
column chromatography' (hexanes-ethyl acetate, 2/ 1).
Further purification of the combined biologically active
fractions by additional silica gel flash column chroma-
tography (methylene chloride-methanol, 20/1) followed
by repeated recrystallization yielded pure divinorins A (1)
(1.2 g) and B (3) (50 mg).8
(3) (a) Wasson, R. G. Bot. Mus. Lea& Haruard Uniu. 1962,20,77.
(b) Hofmann, A. 'LSD: My Problem Child"; McGraw-Hill: New York,
1980, pp 127-144. (c) Valdes, L. J.; Dim, J. L.; Paul, A. G. J. Ethano-
pharmacol. 1983, 7, 287.
(4) (a) Hofmann, A. PZanta Medica 1964,12,341. (b) Diaz, J. L. In
'Etnofarmacologia de Plantas Alucinogenas Latinoamericanas"; Diaz, J.
L., Ed.; Centro Mexican0 de Estudioe en Farmaco-dependencia: Mexico
City, 1975; pp 149-152. Although it was reported that active fractions
reacted with Ludy Tenger reagent (a m d e d Dragendorffs reagent) and
possibly alkaloids, extensive work in our laboratory has shown that the
pharmacologically active extracts from S. diuinorum do not contain al-
kaloids, nor were we able to isolate any alkaloids from the plant itself.
(5) Infusions and tinctures of the green matter from Lagochilua in-
ebriana Bge. are described as having pharmacological activity exhibited
by hemostatic and sedative properties of a general nature that are in part
attributed to the spiro ether-containing labdane, lagochilin, which has
been ieoleted from the plant. However, details regarding activities of the
preparations and the diterpene itself are not available: (a) Abramov, M.
M.; Yaparova, S. A. J. Appl. Chem., USSR 1963,36,2471. (b) Chizhov,
0. S.; Kessenikh, A. V.; Yakolev, I. P.; Zolatorev, B. M.; Petukhov, V. A.
Tetrahedron Lett. 1969, 1361.
(6) Brimblecombe, R. W.; Green, A. L. Nature (London) 1962, 194,
983. The following is a summary of our modified bioassay: Mice were
dosed with various fractions of the extract and the ani" activities were
observed in the field, which consisted of a 3-ft. circle divided into squares.
Parameters measured were the numbers of squares entered (lines
crossed), rearing8 on the hind legs, and time spent immobile. Divinorin
A reduced all three measures of activity, resembling that of S. diuinorum
in human beings."
(7) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.
Divinorin A (l), mp 242-244 OC, [a]22D -45.3' (c 8.530,
CHC13), had the molecular formula Cz3HZ8o8. The UV
spectrum [211 nm ( E 5260)] was indicative of the presence
of the furan moiety. This was further corroborated by the
products from the hydrogenation reaction of divinorin A
which was accompanied by hydrogenolysis at C-12. Thus,
catalytic hydrogenation of divinorin A in methanol over
5% Pd/C provided quantitatively a stereoisomeric mixture
(at C-13) of hexahydro derivatives 4. Although it was
difficult to determine the presence of a ketone group from
the IR spectrum of divinorin A alone, as its carbonyl region
is strongly absorbed due to three other carbonyl func-
tionalities, the presence of a highly hindered ketone group
in divinorin A became evident from the results of its so-
dium borohydride reduction. The sodium borohydride
reduction of divinorin A was found to be extremely sluggish
at room temperature, presumably owing to the severe steric
crowding near the ketone located at C-1. However, re-
duction at higher temperatures produced the mixture of
2 (40%) and its stereoisomeric diol (40%). The latter
appears to be stereoisomeric at C-8 and/or C-9, which
evidently had resulted from its "base-promoted" C-8/C-9
cleavage followed by reclosure prior to the reduction. The
stereochemistry of the diol 2 was secured as identical with
that of divinorin A by its conversion to the latter via
acetylation with acetic anhydride/pyridine, at room tem-
perature, followed by oxidation with pyridinium chloro-
chromate. In contrast, the same sequence of the reactions
of the other diol gave a thus far undetermined stereoisomer
of divinorin A.
Both lH and 13C NMR spectra were particularly in-
formative since all lH and 13C signals could be observed
and assigned through extensive proton decoupling, off-
resonance decoupling, and selective decoupling experi-
ments. These provided partial structures which are in-
dicated in connecting thick lines and by solid blocks de-
noting quaternary carbons in Figure 1A. The linkage
between C-1 and C-10 was ascertained from the lH NMR
spectrum in acetone-d, of the diol 2, mp 218-220 "C, ob-
(8) Purified, recrystallized divinorin A has activity slightly stronger
than the original plant extract, whereas divinorin B was inactive in this
bioassay (this does not preclude the possibility of a different psychotropic
activity in the latter). The mother liquor from recrystallization contains
at least two more terpenoids in addition to these two divinorins. This
mixture shows substantially stronger activity, thus suggesting the pres-
ence of a minor component(s) that either synergistically enhances the
activity of divinorin A or has strong sedative properties in itself. Isolation
of these minor components and identifying their activities is currently
being pursued.
4718 J. Org. Chem., Vol. 49, No. 24, 1984 Notes
CH,OO~ CH3OOC
4 2 R I = H I R2=OH -
3 R I , R2.0
(divinorin B)
tained in 40% yield from divinorin A with sodium boro-
hydride in isopropyl alcohol at 35 "C for 2.5 h. Thus,
inspection of the coupling constants involving protons a t
C-10, C-1, and C-4 (Jlop,lp = 2.0 Hz, Jls,2a = 2.1 Hz, Jzp,ap
Hz) led t o the proposed structure 1 for divinorin A.
This structure was finally confirmed by a single-crystal
X-ray diffraction experiment. A perspective drawing of
the final X-ray model, less hydrogen atoms, is shown in
Figure 2. Details of the X-ray analysis are given in the
Experimental Section and bond lengths, angles, other
crystallographic parameters are provided as supplementary
information.
-3.39O (c 0.441,
EtOH), was found to be desacetyldivinorin A, which was
verified by its conversion into divinorin A via acetylation
with acetic anhydride in pyridine. The absolute configu-
rations are proposed based on the CD spectra (MeOH) of
divinorins A (1) (At294 -2.63) and B (3) -1.41) and
hexahydrodivinorin A (4) -1.67). While the absolute
configurations shown appear to be corroborated by the
negative n - T* Cotton effect of isofructicolone: the un-
ambiguous assignment of the absolute configurations of
the divinorins is yet t o be made.
Experimental Section
Microanalysis was performed by Spang Microanalytical Lab-
oratory, Eagle Harbor, MI. Melting points were taken on a Fisher
Johns melting point apparatus and are uncorrected. The ultra-
violet spectrum was determined on a Hewlett-Packard 8450A
UV/vis spectrophotometer. Infrared spectra were recorded on
a Perkin-Elmer Model 281 spectrometer as potassium bromide
(KBr) disks. Mass spectra were taken with a Finnigan Model
4023 GC/MS spectrometer. Nuclear magnetic resonance spectra
were obtained on a Bruker WM360 spectrometer (360 MHz for
'H and 90.56 MHz for 13C) in CDC1, unless otherwise stated and
all chemical shifts are reported in parts per million relative to
internal tetramethylsilane. Optical rotations were determined
on a Perkin-Elmer 241 polarimeter using a quartz cell of 10-cm
length and 1-mL volume. Circular dichroism spectra were re-
corded on a JASCO J-40A automatic recording spectropolarimeter
using a quartz cell of 20-mm length and 3.5-mL volume.
Collection, Extraction, and Isolation. Live specimens of
S. divinorum were collected at Cerro Quemado (Sept 3,1979) and
Cerro Rabon (March 7, 1980) in Oaxaca, Mexico. The plants were
cultivated at the Matthaei Botanical Gardens, The University
of Michigan, in order to provide material for research.
Fresh Salvia leaves (5.350 kg) were lyophilized and forced
through 7- and 16-mesh screens yielding 674.1 g of powdered dry
material. The powder was extracted in 30-40-g lots for 24 h with
ethyl ether (1 L/lot) using a Soxhlet apparatus and dried in vacuo,
giving a total of 27.51 g of ether extract. The extract was par-
titioned between hexanes (600 mL) and 90% aqueous methanol
(600 mL) for 48 h using a liquid/liquid extractor and yielded, after
= 4.9 Hz, J2p,3a = 11.4 Hz, J3p,4p = 2.1 Hz, and J3a,4p = 13.2
Divinorin B (3), mp 213-216 O C ,
Figure 2. Computer-generated perspective drawing of divinorin
A (1) with crystallographic numbering scheme.
removal of the solvent in vacuo, a 7.41-g methanol fraction. The
hexane fraction was repartitioned as above and the combined
concentrated methanol fractions (9.36 g) were subjected to further
purification by flash column chromatography.
In a typical experiment, a Fischer Porter 2.5 X 25 cm column
containing 55 g of silica gel (70-230 mesh), which had been treated
with 2.75 mL of water, was equilibrated with the eluting solvent,
hexanes/ethyl acetate (2/ 1). Fivehundred milligrams of the
methanolic fraction was adsorbed on 5 g of silica gel and carefully
poured on the preequilibrated column. The eluting solvent was
then forced (using nitrogen pressure) through the column at the
flow rate of 25-35 mL/min and 100-mL fractions were collected.
Each fraction was followed by bioassay, and fractions 4-9 were
determined to be active. The 9.36 g of methanolic fraction yielded
2.349 g of desired crude material. The material recovered was
further purified by using another flash column chromatography.
Fivehundred milligrams of the crudely purified methanol fraction,
adsorbed on 5 g of silica gel, was added to the top of the 2.5 X
25 cm Fischer Porter column containing 55 g of silica gel which
had been treated with 2.75 mL of water and preequilibrated with
the eluting solvent, methylene chloride/methanl (20/ 1). The
column was eluted at a rate of 25-35 mL/min with the aid of 5
psi of nitrogen pressure, and 25-mL fractions were collected. The
biologically active fractions (fractions 3-5) were combined. The
2.349 g of starting material gave 1.515 g of impure diterpene
mixture from which pure divinorin A (893 mg) was obtained after
two recrystallizations from absolute ethanol. The combined
mother liquors were subjected to preparative TLC purification
(Merck GF-254, 15 X 1 mm plate, 20 X 20 cm, developed with
CHCl3/MeOH/HZ0, 100/10/1), which gave more divinorin A (305
mg; R, 0.63) and crude divinorin B. The crude divinorin B was
further purified by two recrystallizations from methanol, yielding
50 mg of divinorin B (Rf 0.48). Divinorin A (1): mp 242-244
"C; [alZzD -45.3" (c 8.530, CHC1,); UV (MeOH) 211 nm ( e 5260);
IR (KBr) 3220, 1745, 1735, 1240, 875 cm-'; NMR (lH and 13C)
see Figure 1; mass spectrum (EI; 70 eV), m / z 432 (M', 1.5), 273
(6.5), 166 (8.6), 121 (13.0), 108 (8.0), 107 (9.7), 95 (17.9), 94 (loo),
93 (9.9), 91 (6.9), 81 (11.2), 79 (5.5), 55 (13.7); CD (MeOH)
-2.63. Anal. Calcd for C23Hz8O8: C, 63.89; H, 6.48; 0, 29.63.
Found C, 63.44; H, 6.61; 0,30.14. Divinorin B (3): mp 213-216
"C; [ C Y ] ~ D -3.39" (c 0.441, EtOH); IR (KBr) 3495,3140,1735,1715,
1250,860 cm-'; 'H NMR (360 MHz) 6 1.101 (s, 3 H, 19-H), 1.484
(s, 3 H, 20-H), 1.50-1.65 (m, 3 H, 7-Hs and 11/3-H), 1.797 (ddd,
1 H, J = 2.7, 3.1, 12.9 Hz, 6a-H), 2.020 (ddd, 1 H, J = 11.4, 13.5,
13.6 Hz, ~ c Y - H ) , 2.074 (dd, 1 H, J = 2.0, 11.7 Hz, 8-H), 2.169 (9,
1 H, 10-H), 2.17 (m, 1 H, 68-H), 2.480 (ddd, 1 H, J = 3.1,7.7, 13.6
(9) Mhinez-Ripoll, M.; Fayos, J.; Rodriguez, B,; Garcia-Alvarez, M. Hz, 3b-H), 2.548 (dd, H, = 5*27 13.4 Hz, 2'709 (dd,
C.; Savona, G.; Piozzi, F.; Paternostro, M.; Hanson, J. R. J. Chem. SOC.,
Perkin Trans. 1 1981, 1186.
1 H, J = 3.1, 13.5, 4-H), 3.599 (d, 1 H, J = 3.3 Hz, OH), 3.717 (s,
3 H, COOMe), 4.080 (ddd, 1 H, J = 3.3, 7.7, 11.4 Hz, 2-H), 5.567
Notes J . Org. Chem., Vol. 49, No. 24, 1984 4719
dried over sodium sulfate, and evaporated in vacuo. The crude
mixture (35 mg) was purified via flash column chromatography
(50 g of 230-400 mesh silica gel; eluted with hexanes/ethyl acetate
(1/1)), providing 21 mg of diol 3 2-monoacetate along with 2 mg
of the starting diol 3. Diol 3 2-monoacetate: IR (KBr) 3600,
1740,1735,1240 cm-'; 'H NMR (360 MHz) 6 1.002 (s, 1 H, lO-H),
1.390 (s, 3 H), 1.458 (s, 3 H), 2.096 (s, 3 H, OAc), 3.677 (s, 3 H,
COOMe), 4.292 (br s, 1 H, 1-H), 4.696 (ddd, 1 H, J = 3.2,4.6,11.7
Hz, 3-H); 13C NMR (90.56 MHz) 6 16.81, 17.90,18.72, 21.07, 24.90,
36.96, 37.87, 40.66, 51.43, 52.58, 55.00, 55.88, 67.36, 71.75, 74.60,
108.47, 125.91, 139.39, 143.78, 169.61, 171.68, 172.44.
The diol 3 2-monoacetate (19 mg), dissolved in 5 mL of
methylene chloride, was placed in a 25-mL round bottomed flask
and treated with 53 mg of PCC in 5 mL of methylene chloride
at room temperature. After 30 h, the reaction mixture was diluted
with 50 mL of ether. The ether layer was recovered by decantation
and the dark residue was extracted with 10 mL of ether. The
combined ether layers were dried over sodium sulfate and the
organic solvents removed in vacuo. The crude reaction products
(20 mg) were purified via flash column chromatography (55 g of
Merck silica gel, 230-400 mesh; eluted with hexane/EtOAc (3/2)
which yielded 10 mg of divinorin A (1) and 5 mg of diol 3 2-
monoacetate.
Acetylation of Divinorin B (2). Divinorin B (10 mg) dis-
solved in 5 mL of dry pyridine and placed in a 10-mL round
bottomed flask, was treated with 0.5 mL of acetic anhydride at
room temperature. The mixture was stirred for 6 h at that
temperature. The reaction was terminated by addition of 1 mL
of methanol and the mixture poured into ice water (50 mL). The
resulting precipitates were collected by filtration, washed thor-
oughly with water, and dried in vacuo. The crude product was
recrystallized from absolute ethanol and found identical with
divinorin A.
X-ray Crystallographic Analysis of Divinorin A (1).
Crystals of divinorin A were obtained by slow cooling of a satu-
rated ethanolic solution. A crystal of dimensions 0.078 X 0.269
x 0.418 mm was mounted on a Syntex P2, diffractometer and
found to have the space group P2,2,2, with a = 6.369 (2) A, b =
11.366 (4) A, and c = 30.747 (12) A. The density was calculated
to be 1.29 g/cc for 2 = 4. Intensity data were obtained using Mo
Ka radiation monochromatized by means of a graphite crystal
whose diffraction vedor was perpendicular to the diffraction vector
of the sample. A total of 2494 reflections with 20 < 50" were
measured, of which 1376 were considered observed [ I > 3u(I)].
The data were reduced by procedures previously used.l0 The
structure was solved using MULTAN~E. Hydrogen atomic positions
were calculated and added to the structure. They were given
isotropic temperature factors one unit greater than the atom to
which they are attached and their positions were not refined.
Standard techniques were used to refine the structure to R1 =
0.087 and R2 = 0.092.
Note Added in Proof. After the original submission of
the manuscript, we learned that Ortega et al. reported the
structure of salvinorin which is identical with that of di-
vinorin A described herein (Ortega, A.; Blount, J. F.;
Manchand, P. S. J. Chem. SOC., Perkin Trans. 1 1982,
2505). Therefore, divinorins A and B should be called
salvinorins A and B, respectively.
Acknowledgment. We are greateful t o the National
Science Foundation and the University of Michigan for
their contributions to the purchase of a Bruker 360-MHz
NMR and Finnigan 4023 GC/MS spectrometer. L.J.V.
is grateful for a Lilly Endowment Fellowship in Pharmacy
during the course of this work.
Registry No. 1, 83729-01-5; 2, 92545-29-4; 3, 92545-30-7; 4,
Supplementary Material Available: Final positional pa-
rameters with estimated standard derivations are shown in Table
I; anisotropic thermal parameters with their standard deviations
92545-31-8.
(dd, 1 H, J = 5.1, 11.7 Hz, 12-H), 6.376 (dd, 1 H, J = 0.92, 1.8
Hz, 14-H), 7.399 (dd, 1 H, J = 1.5, 1.8 Hz, 15-H), 7.416 (dd, 1 H,
J L- 0.92, 1.5 Hz, 16-H); 13C NMR (C&,N; 90.56 MHz) 6 15.35
(q), 16.49 (q), 18.89 (t), 35.82 (t), 38.31 (s), 42.44 (s), 43.53 (t), 51.22
(d), 51.51 (q), 53.62 (d), 63.18 (d), 71.99 (d), 75.27 (d), 109.31 (d),
126.64 (s), 140.26 (d), 144.15 (d), 171.38 (s), 172.59 (s), 209.79 (s)
ppm; CD (MeOH) Aczw -1.41.
Hexahydrodivinorin A (4). A mixture of 150 mg of divinorin
A (1) in 100 mL of methanol and 162 mg of 5% palladium on
charcoal in a 125-mL round bottomed flask was hydrogenated
at room temperature under a slightly positive pressure for 24 h.
The catalyst was removed by filtration and the solvent removed
in vacuo. The residual oil was dissolved in 25 mL of methylene
chloride and extracted 3 times with 5mL portions of 1% NaHC03
in HzO. The combined aqueous layers were acidified to pH 1.0
with concentrated HC1 and extracted 3 times with 5-mL portions
of methylene chloride. The organic fraction was taken to dryness
in vacuo and the crude oily product was recrystallized from
ethanol-water to provide pure hexahydrodivinorin A (4) (143 mg):
mp 196-198 "C; IR (KBr) 3100,1755,1735,1725,1225 cm-'; 'H
NMR (360 MHz) b 1.033 (8, 3 H), 1.340 and 1.345 (both s, total
3 H), 2.137 and 2.139 (both s, total 3 H), 3.686 (8, 3 H); 13C NMR
(90.56 MHz) 6 15.99 (q), 19.71/19.74* (q), 20.48 (q), 21.26 (t),
27.19/27.27* (t), 31.33 (t), 32.10/32.22* (t), 38.10 and 38.29
(multiplicities not certain due to overlap), 38.19 (s), 38.37 (t),
39.56/39.63* (d), 42.91*/42.92 (e), 49.05*/49.08 (d), 51.71 (q),
54.02*/54.15 (d), 58.67*/58.79 (d), 67.84 (t), 73.31*/73.37 (t),
75.44*/75.45 (d), 169.61 (s), 171.65 (s), 177.26*/177.49 (s),
202.08/202.10* (s) (the paired chemical shifts represent those of
spectroscopically resolved diastereomers, and the ones with as-
terisks indicate the more intense 13C peaks between the two
paired); mass spectrum (CI; CH,), m/z (relative intensity) 467
(12), 440 (22), 439 (M + H+; 100); 437 (ll), 422 (15), 421 (681,167
(6), 104 (17), 99 (8),97 (61, 95 (7),85 (9); CD (MeOH) Aem6 -1.67.
Sodium Borohydride Reduction of Divinorin A. Divinorin
A (1; 260 mg) was dissolved in 120 mL of isopropyl alcohol in a
200-mL round bottomed flask and was treated with 14 mg of
sodium borohydride. The mixture was warmed up to 33-35 "C
and was kept at that temperature for 2.5 h. The reaction was
terminated by addition of 3 mL of methanol. The solvent was
removed under vacuum and the dried crude products were re-
dissolved in 50 mL of chloroform and washed with 50 mL of 1 %
HC1 and twice with 50-mL portions of water. The organic fraction
was dried over sodium sulfate and taken to dryness (255 mg). The
crude mixture was p d i e d through flash column chromatography
on silica gel (230-400 mesh; 30 g) using hexanes/ethyl acetate
(1/2) as the eluting solvents. The more polar diol (2; 124 mg)
was recovered along with the less polar, thus far unidentified
stereoisomeric diol (120 mg; mp 234-235 "C). Diol 2 mp 218-220
"C; [aIBD +1.16" (c 1.55, EtOH); IR (KBr) 3505,1725,1705 cm-';
'H NMR (acetone-&; 360 MHz) 6 1.163 (s, 1 H, 10-H), 1.375 (s,
3 H), 1.438 (s, 3 H), 1.56-1.62 (m, 4 H, 3@H, 6-H's and 7a-H),
1.799 (dd, 1 H, J = 11.9, 13.2 Hz, llP-H), 1.964 (dddd, 1 H, J =
3.3,3.3,3.5, 13.8 Hz, 7@-H), 2.109 (ddd, 1 H, J = 11.4, 12.7, 13.2
Hz, 3a-H), 2.203 (dd, 1 H, J = 2.1,13.2 Hz, 4-H), 2.294 (dd, 1 H,
J = 3.3, 12.3 Hz, 8-H), 2.494 (dd, 1 H, J = 5.6,13.2 Hz, lla-H),
3.358 (br s, 1 H, 1-OH), 3.553 (dddd, 1 H, J = 2.0,4.9, 5.4, 11.4
Hz, 2-H), 3.623 (s, 3 H, COOMe), 4.027 (d, 1 H , J = 5.4 Hz, 2-OH),
4.207 (br s, 1 H, 1-H), 5.594 (dd, 1 H, J = 5.6, 11.9 Hz, 12-H),
1.8 Hz, 15-H), 7.650 (dd, 1 H, J = 0.7, 1.6 Hz, 16-H); 13C NMR
(acetone-d6; 90.56 MHz) 6 17.02 (q), 18.07 (q), 19.71 (t), 29.39 (t),
37.39 (s), 38.50 (s), 41.22 (t), 44.75 (t), 51.24 (q), 52.79 (a), 55.81
(d), 56.05 (d), 69.69 (d), 72.12 (d), 72.33 (d), 109.70 (d), 127.74
(s), 140.62 (d), 144.52 (d), 172.12 (s), 173.75 (s); mass spectrum
(CI; CH4), m/z (relative intensity) 421 (7), 394 (21), 393 (M +
H', loo), 375 (74), 357 (78), 343 (87).
Conversion of Diol 3 to Divinorin A (1). The diol 3 (25 mg)
was dissolved in 7 mL of dry pyridine, placed in a 25-mL round
bottomed flask, and treated with 1 mL of acetic anhydride. After
being stirred at room temperature for 5 h, the reaction was ter-
minated by addition of 1 mL of methanol. The mixture was
poured into ice water (50 mL), its pH was adjusted to -10 by
addition of aqueous NH40H and it was extracted twice with
60-mL portions of chloroform. The combined organic layers were
washed with 25 mL of 10% aqueous HCl and then 25 mL of water,
6.593 (dd, 1 H, J = 0.7, 1.8 Hz, 14-H), 7.556 (dd, 1 H, J = 1.6,
(IO) Butler, W. M.; Tanaka, Y.; Koreeda, M. J. Org. Chem. 1981,46,
4620.
4720 J. Org. Chem. 1984,49, 4720-4721
are listed in Table 11; Table I11 lists the crystallographically
determined bond distances and angles (Tables 1-11) (listings of
observed and calculated structure factors amplitudes are available
from the authors); a figure which shows a computer-generated
stereodrawing with anisotropic thermal ellipsoids of the compound
(5 pages). Ordering information is given on any current masthead
page.
Preparation of cy-Fluoro Enolates and Their Use
in the Directed Aldol Reaction
John T. Welch,* Karl Seper, Seetha Eswarakrishnan, and
Janet Samartino
Department of Chemistry, State University of New York at
Albany, Albany, New York 12222
Received April 4, 1984
Although the directed aldol reaction has been the subject
of much investigation,l surprisingly little has been reported
about the stereochemistry of a-heteroatom substituted
enolates and their utilization in directed aldol reactions.
The stereoselective formation of olefins by the aldol
products of silyl-substituted enolates2 on warming has
engendered speculation that formation of the aldol product
is itself diastereoselective.2d Stereoselectively formed
a-amino en~latesl*,~ may react with high diastereoselec-
t i ~ i t y . ~ In contrast, neither the stereochemistry of mo-
nohalogenated enolates6 nor their diastereoselectivity in
aldol reactions has been reported.
Results and Discussion
We have found that the lithium enolate of ethyl fluor-
oacetate may be readily prepared and efficiently utilized
in the directed aldol reaction6 (Table I). The utility of
the fluoroacetate residue in compounds such as y-fluoro-
glutamic acid or fluorocitric acid in discerning biochemical
pathways has been limited by the difficulty of constructing
the fluorinated molecules. We are currently exploring the
use of this anion in the stereoselective synthesis of such
specifically fluorinated natural products, where substitu-
tion by fluorine has a little steric effect but a pronounced
electronic effect on the properties of the molecule. Much
early work has been reported on the use of ethyl fluoro-
acetate in synthesis but with no indication of stereochem-
istry and often under conditions where the fluorohydrin
would not survive.' Previously ethyl bromofluoroacetate,
(1) (a) Evans, D. A; Nelson, J. V.; Taber, T. R. Top. Stereochem. 1982,
13,l-115. (b) Mukaiyama, T. Org. React. (N.Y.) 1982,28,203-331. (c)
Mukaiyama, T. Pure Appl. Chem. 1983,55,1749-1758. (d) Heathcock,
C. H. In "Comprehensive Carbanion Chemistry"; Buncel, E., Durst, T.,
Eds.; Elsevier: Amsterdam, 1984; Part B, Chapter 4.
(2) (a) Shimoji, K.; Taguchi, H.; Oshima, K.; Yamamoto, H.; Nozaki,
H. J. Am. Chem. SOC. 1974,96,1620-1621. (b) Hartzell, S. L.; Rathke,
M. W. Tetrahedron. Lett. 1976,2757-2760. (c) Larson, G. L.; Quiroz, F.;
Suarez, J. Synth. Commun. 1983, 13, 833-844. (d) Larcheeveque, M.;
Debal, A. J. Chem. SOC., Chem. Commun. 1981, 877-879.
(3) Garst, M. E.; Bonfiglio, J. N.; Grudoski, D. A.; Marks, J. J . Org.
Chem. 1980,45, 2307-2315.
(4) Shanzer, A.; Somekh, L. Butina, D. J . Org. Chem. 1979, 44,
(5) (a) House, H. 0.; Fischer, W. F.; Gd, M.; McLaughlin, T. E.; Peet,
N. P. J. Org. Chem. 1971,36,3429-3437. (b) Kowalski, C.; Creary, X.;
Rollin, A. J.; Burke, M. C. J. Org. Chem. 1978,43, 2601-2608.
(6) Ethyl fluoroacetate is extremely poisonous, causing convulsions,
and ventricular fibrillation. It was only handled by using syringe tech-
niques in an efficient fume hood.
(7) (a) Bergmann, E. D.; Cohen, S.; Shahak, I. J. Chem. SOC. 1955,
2190-2193. (b) Bergmann, E. D.; Cohen, S.; Shahak, I. J. Chem. SOC.
1959,3278-3285. (c) Bergmann, E. D.; Schwarcz, J. J. Chem. SOC. 1956,
1524-1527. (d) Bergmann, E. D.; Szinai, S. J. Chem. SOC. 1956,
1521-1524. (e) Bergmann, E. D.; Cohen, S.; Shahak, I. J. Chem. SOC.
1959, 3286-3289. (0 Bergmann, E. D.; Chun-Hsu, L. Synthesis 1973,
44-56. (9) Bergmann, E. D.; Cohen, S. J. Chem. SOC. 1961, 3537-3538.
(h) Kent, P. W.; Barnett, J. E. G. J. Chem. SOC. 1964, 2497-2500.
3967-3969.
Scheme I
0
1
0
EtO; b H 3
Scheme I1
E
LiO-F
EtOAH
_c
F
2
in a Reformatsky reaction, and the lithium enolate of
tert-butyl fluoroacetate were used in the preparation of
fluorocitrate8 and fluorohomocitric acid: respectively. In
both reports, difficulty in the preparation of the lithium
enolate of ethyl fluoroacetate or very low yields in the
attempted directed aldol reaction of the lithium enolate
were described. For the introduction of the fluoroacetate
residue, commercially available ethyl fluoroacetate where
the ester function can be easily manipulated further is the
reagent of choice.
In contrast to the low yields of aldol product reported
upon enolate formation with lithium diisopropylamide
(LDA) at -78 "C in the presence of 1 equiv of hexa-
methylphosphoric triamide (HMPA), generation of the
enolate with lithium hexamethyldisilazide (LHMDS) at
-78 "C resulted in consistently higher yields of aldol
products (eq 1 and 2). Furthermore it was observed that
CH2FC02CH2CH3 + LHMDS - LiCHFC02CH2CH3
(1)
RR'COHCHFCO2CH2CH3 (2)
LiCHFC02CH2CH3 + RR'CO -
generation of the base with methyllithium-lithium brom-
ide complex in diethyl ether resulted in higher yields than
when the base was isolated in the conventional manner.'O
Success in the generation of the enolate with LHMDS led
to our reexamination of the reaction with LDA. Compa-
rable yields of aldol products were isolated when the
enolate was formed with LDA at -105 "C in the presence
of HMPA. The enolate may be trapped with chlorotri-
methylsilane to form the corresponding silyl enol ether (eq
3). The ratio of the E:Z enolate was found to be 1:l by
LiCHFCO2CH2CH3 + (CH3)3SiC1 - CHF=C(OCH,CH,)(OSi(CH,),) (3)
'H NMR spectroscopy.l' Not unexpectedly, the enol silyl
ether-fluoroketene acetal was observed to decompose
(8) Brandiilnge, S.; Dahlman, 0.; Morch, L. J. Am. Chem. Soc. 1981,
(9) Molines, H.; Massoudi, M. H.; Cantacuzene, D.; Wakselman, C.
(10) Rathke, M. W. J. Am. Chem. SOC. 1970,92, 3222-3223.
(11) Chemical shifts are reported in ppm from Me,Si in carbon tet-
103, 4452-4458.
Synthesis 1983, 322-324.
rachloride solution: 6.2, JH,F = 77 Hz; 6.32, JH,F = 74 Hz.
0022-3263/84/1949-4720$01.50/0 0 1984 American Chemical Society
The Structure of Sarisan, an Isomer of Myristicin, Isolated
from the Leaf Oil of Beilschmiedia miersii
The structure of the principal component in the leaf oxy-4,5-methylenedioxy benzene, 11, and named
oil from Beilschmiedia miersii, an avocado relative
from Chile, has been deduced to be 1-allyl-2-meth-
sarisan.
mall samples of the principal component in the oil that is
steam distilled from the leaves of Beilschniiedia miersii S (Gay) Kosterm. can be isolated by gas chromatography.
The mass spectrum indicated a molecular weight of 192 and the
material was first believed to be a previously reported natural
product, myristicin. However, comparison with an authentic
sample, isolated from oil of myristica, proved that the two
were not identical. Because of the current interest in the
chemistry of natural phenols and their toxicity to animals
and related physiological activity (Singleton and Kratzer,
1969; Truitt et ai., 1961), the question of the structure of this
oil, which we called sarisan, was pursued further.
EXPERIMENTAL
Infrared absorption spectra were obtained with a Beckman
IR-12 using a 0.05 mm path micro cell with a neutral density
in the reference beam.
Nmr spectra were obtained with a Varian Model-T spec-
trometer.
Mass spectra were obtained with a Hitachi Perkin-Elmer
RMU-6D in the Chemistry Department.
Washed leaves were ground in a Waring Blendor and steam
distilled under reflux using a Clevenger collection trap for
oils lighter than water.
A Loenco gas chromatograph Model 15-B using a lI4-in. X
5-ft polydiethylene glycol succinate column, isothermally
at 175' C, elutes sarisan in 26 min, and myristicin in 32 min
with 40 cc/min helium as the carrier gas.
A sample of oil from a 20 ~1 injection was collected in a
1.8 X 100 mm melting point capillary tube at the exhaust port
using dry ice. The infrared, nmr, and mass spectra, and ele-
mental analysis were determined: ir (CCl?) cm-' 3088, 1645,
substituted phenyl); nmr (CClJ 6 6.53 (s, 1, aromatic H),
6.36 (s, 1, aromatic H), 5.80 (s, 2, 0-CH2-0), ca. 5.80
(m, 1, C-CH=C), 4.90 (d, 2, J = 14 Hz, C = CHZ), 3.70
1012, 919 (--CH=CHz), 2784 (0-CHZ-0), 863 (1, 2, 4, 5
(s, 3, 0-CH,), 3.20 (d, 2, J = 6Hz, C-CH2-C); mass
spectrum 80 ev n7 'e 192 parent ion.
Anal. calcd. for CilHI2O3: C, 68.73; H, 6.30.
Found: C, 69.01; H, 6.20.
Oil of myristica was purchased from Dodge and Olcott
Inc., New York, N.Y. The highest boiling oil was recog-
nized as myristicin from its infrared, nmr, and mass spectra
and refractive index; ir (CC14) cm-l 3090, 1636, 998, 922
(-CH=CHz), 2784 (O-CH2-O); nmr (CC14) 6 6.22 (s,
2, aromatic-H), 5.80 (s, 2, 0-CH2-0), ca. 5.80 (m, 1,
O-CH3), 3.18 (d, 2, J = 6Hz C-CH2-C); mass spectrum
80 ev mje 192 parent ion; ng 1.5400; bp 94-95' (.45 mm);
[lit. (Heilbron et al., 1965) n g 1.5403; bp 95-97' C (.2 mm)].
C-CHzC), 4.96 (d, 2, J = 12 Hz, C = CH?), 3.80 (s, 3,
DISCUSSION
Only small differences exist in the data comparing sarisan
with myristicin. The parent ion is the same and the frag-
mentation pattern of the two compounds in their mass spectra
are very similar.
The nmr spectra of sarisan and myristicin bear a strong
resemblance to that of safrole (Bhacca et a/., 1962) and the
identification for the methylenedioxy and allyl group was
straightforward. Both sarisan and myristicin have an addi-
tional methoxyl group resonance in the appropriate region.
The aromatic hydrogens in myristicin coincide in a singlet
absorption as is the case for safrole. However, the two
aromatic hydrogens in sarisan appear as separated singlets
and this establishes that its structure must differ from myris-
ticin.
Three of the six possible isomers, IV, V, and VI, which
come into consideration (Figure 1) can be eliminated because
they have adjacent aromatic hydrogens which should show
a pair of doublets in their nmr spectra. Myristicin, I, is ruled
out by direct comparison and this leaves only two possibilities.
The two differ in that one is a 1,2,4,5-substituted benzene,
544 J. AGR. FOOD CHEM., VOL. 18, NO. 3, 1970
, 1-
I m
CH30
m Y ??ZZT
Figure 1. Isomers of mgristicin
and the other is a 1,2,3,5-~ubstituted derivative. Sarisan
has a strong infrared absorption at 863 cm-l, which is in the
characteristic region for a 1,2,4,5-substituted benzene ring
(Nakanishi. 1964).
We concluded that the structure of sarisan is l-allyl-2-
methoxy-4,5-methylenedioxy benzene, 11. The trimethoxy
derivative corresponding to myristicin is known as elemicin
and a trimethoxy derivative corresponding to sarisan with the
double bond isomerized into conjugation is known as asarone
(Baxter c??t a/., 1962).
The original plant material was groun at the Southcoast
Field Station, University of California, field 5-2-20, CH-12
from seed collected in Chile by G. A. Zentmeyer. A voucher
specimen (Scora 3068) is on file in the herbarium of the Citrus
Research Center at Riverside.
ACKNOWLEDGMENT
The excellent technical assistance of Mrs. Sari R. Jeske is
gratefully acknowledged.
LITERATURE CITED
Baxter, R. M.. Fan, M. C.. Kandel, S. I., Cwi. J . Clreni. 40, 154
(1 962).
Bhacca, N. S.. Johnson, L. F., Shoolery. J. N.: ??High resolution
nmr spectra catalog,? Varian Associates, Spectrum No. 253, 1962.
Heilbron. I., Cook, A. H.. Bunbury, H. M.. Hey, D. H., ??Dictio-
nary of Organic Compounds,? Oxford Univ. Press, New York.
p. 2363, 1965.
Nakanishi, K., ??Infrared Absorption Spectroscopy,? Holden Day
Inc., San Francisco, p. 27, 1964.
Singleton, V. I.. Kratzer. F. H., J. AGR. FOOD CHEW 17, 497 (1969).
Truitt, Jr.. E. B.. Callaway, 111. E.. Braude. M. C.. Krantz. Jr..
J. C.. J . Nrirropsycliiaf. 2, 205 (1961).
J. Kumamoto
R. W. Scora
Department of Vegetable Crops and
University of California
Riverside, Calif. 92502
Department of Horticultural Science
Receiceil for rcview January 23, 1970. Accepted Murch 10, 1970.
J . AGR. FOOD CHEM., VOL. 18, NO. 3, 1970 545
listen, I'm begging you to never post a post like those again...just annoying^^
Alwrit I'll work on it.
Did we finally come to the conclusion that there is NO DMT IN SALVIA!
Why yes, yes we did
haha, man I was just playin around, take take me seriously
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Old Jul-07-2005, 19:30
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Dick Justice Dick Justice is offline
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Why yes, yes we did
Did we? I've heard it has tiny amounts of dmt too, I just can't seem to find the source of that info.
^ sorry if that lazy method of quoting is hard to read. =P
Yeah well we concluded that because I can't find where I read that, so if anybody ever finds it then we shall make some sort of re-conclusion.
i was looking to see if i could find out if there is dmt in salvia and found this....sounds like a cool job
"Currently, Dennis McKenna is working with the Heffter Organization (http://www.heffter.org) on several projects. He will be working to find out if the actual isolate of Salvia divinorum, Salvinorin-A, is neurotoxic (as some have feared), or neuroprotective (as many now are thinking). He has been working with the UDV, in Brazil, to help identify any long-term side-effects (positive or negative) of chronic Ayahuasca use. And, he is continuing to search for more psychoactive drugs, for therapeutic and mental exploratory uses."
but i found out that
the chemical that makes you trip is salvinorin...NOT DMT
here generally what i found out in small points.
-1982 the chemical salvinorin was isolated from the plant in Mexico.
-2 years later they found the same chemical in america along with its "desacetyl derivative"(<--WTF??)??naming these divinorum A and divinorum B. the guy who isolated they got name priority and called them salvinorin A and salvinorin B
-he later discovered Salvinorin C
-Later experiments by Jonathan Ott noted a 100 microgram threshold dose of salvinorin A and that there was definite psychoactivity
-B and C to this day have never been properly tested on humans...but it is speculated that salvinorin C??which appears in the plant at only about 10% the amount of salvinorin A??may be even more potent
-B is speculated to be inactive....
That much I knew, I was just wondering if there are trace amounts of DMT ( Not enough to be active.) in salvia divinorum as well because I thought I remembered reading that in the past. I'm pretty sure there isn't any though, as i have been unable to find any documentation that suggests there is.Quote:
but i found out that
the chemical that makes you trip is salvinorin...NOT DMT
Delta, could you please quit posting long articles that have nothing to do with the subject at hand, in the mistaken belief that you are impressing someone? Feel up to a flame war? Choose the topic. By the way, has anyone heard from Dick Justice, I haven't heard from him in a while.
Holy canoley an old fashioned showdown!? You've got balls jaysin, real grade a testicles.Quote:
Originally Posted by andruejaysin
Pretty sure there's not but you can always check out Daniel Siebert's site for the info. I read up on it a lot before I tried it:Quote:
Originally Posted by Edgar
http://www.sagewisdom.org
Like I said, I'm pretty sure there is no other known psychoactive in SD besides salvinorin, they've been looking for one for twenty years or so.
Yeah, I've got balls, but more importantly, I have the knowledge.