Salvinorin A

[nepenthes]

I grow Salvia divinorum and am rather interested in this chemical (Salvinorin A). I've been doing a lot of research on it lately but have not found any info that even comes close to proposing a synthesis for it. Various searches here at the Hive have also yielded nothing in regards to my query. Have any fellow bees thought at all about this wonderous chemical, which is not only totally legal but very very strong (active at microgram range - almost as powerful as LSD)? Any thoughts on the subject of Salvinorin A and its synthetic production would be greatly appreciated!

-nepenthes

[Osmium]

As far as I remember it contains 4 stereo centers, which causes its synth to be pretty much impossible. You have to employ ways to ascertain correct stereochemistry, or you will end up with a minuscule amount of active product. The telvoid once tried to impress us with his ideas to synthesize it, way back before he started to stir up shit here. Didn't he have a website where he posted that crap for everybody to see? Does it still exist?

[Teonanacatl]

yea...pure salvinorin is easiest to get hold of via extraction followed by chromatography...I've wondered about syntheses starting with other common triterpenoids like salviarin, but even if you came up with something like this you would still have to purify salviarin...only real advantage is that it would be easy to extract large quantities of salviarin at once....look at the similarities between the two here:
 

http://salvia.lycaeum.org/ortega82.html

...I think one of the major problems with these is the chiral centers at C-12 and C-8...correct me if I'm wrong...

[Teonanacatl]

one more...
 

http://salvia.lycaeum.org/splendens.html

[Teonanacatl]

HEY! Osmium! This what you were referring to?
 

http://www.linuxstart.com/~prion/chemistry.htm

[Rhodium]

Yes, that's what Osmium meant.

[nepenthes]

Actually Osmium, Salvinorin A has 7 stereo centers, so I guess everyones input about the impossibility of producing this chemical via normal organic chemistry is not baseless. I was thinking along the lines of synthetically producing Salvinorin A in genetically altered E. coli. The steps and procedures needed to obtain Salvinorin A through the use of genetic engineering would probably be much simpler than the method for obtaining it through countless complex chemical reactions. After the initial trouble and effort is put into creating a strain of E. coli with the DNA coding for Salvinorin A in it, it would take a very minimal amount of effort to mantain large pools of the bacteria, force them to produce the maximum amount of Salvinorin A, lyse the cells, and collect the prized product.

All we need is one person to take the initial steps in isolating and then implementing the gene coding for Salvinorin A into an E. coli plasmid. After that it would not be too far of a stretch to think that others would pay top dollar for a culture of this genetically enhanced bacteria from the original producer. The same thing could be done to produce everything from mescaline (from Trichocereus peruvianus DNA) to LSA (from Hawaiin Baby Woodrose DNA) and even psilocybin and psilocin (from the DNA of innumerable Psylocybe mushrooms). The possibilities of genetic engineering in regards to our underground trade are only limited to the available genetic code of psychotropic plants already present in nature.

Unfortunately though, it seems that I have not and will not find an answer (other than my own) in regards to Salvinorin A production here in the Serious Chemistry Forum. How does the proposal of a Biotech (genetic engineering, chemical pathways, etc) Forum sound to the almighty Pimp Bees?

Keep your contributions coming...

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nepenthes@hushmail.com

[Dope Amine]

Hey nepenthes, check out

http://users2.50megs.com/tomahigk/

  .  I think you might find it interesting, although they haven't proved to me that they really did it (you'll see).

[LaBTop]

I believe you allready found your forum, and nobody stops you in posting as much interesting material about it as you can, in the beginning you will find perhaps a handfull of people reacting on it, but it will attrack more knowledgeable people from the outside.
And bio-engineering will be the next hurdle to take for curious Hivers, if they want to keep alongside boundary breaking new sciences.

I started a small company once for cloning orchids, and the curiosity has never left me.
With a few flow cabinets and some good proper labskills you can produce literally hundredthousands of genetically identical plants in about 3-6 months, starting from one plant with the best genetical properties.
Those phaleonopsis with their beautiful big white waxy flowers, made from seed material or meristheem, impressive. And all those other species, a love for botany you will never loose. We Dutchmen know how to grow flowers. Look at our export all over the world. LT/ 

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WISDOMwillWIN

[nepenthes]

Hey LabTop, I've also done quite a bit of cloning of plants myself, and I've been fooling around with fungi genetics... its quite interesting stuff. Besides the other dozen projects or so that I have going now I am looking into making this mass Salvinorin A production a reality. I found out that my school has a few cheap but working gel electrophoresis units, centrifuges, column setups etc, so if I find the time I am gonna try to put some serious work into this during the summer. Locating the gene in the Salvia divinorum DNA that codes for the chem in question will be the hardest part... if anyone can help with the research aspect of this or has any info that may be useful please e-mail me or respond to this thread.

Genetic engineering is rather new to me (computer programming is my thing) but I don't think it should be too tough once things are underway. I have resolved to do this and will devote as much time to it as I can, I guess I will keep you all updated as my project progresses. Again... all help will  be greatly appreciated (refs + direct experience + suggestions/facts).

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nepenthes@hushmail.com

[Artful Dodger]

Nepenthes,

I have to agree that the idea of putting the Salvinorin A coding region of DNA into bacterial plasmids is a great idea, but it would take at least a year of work. I'm doing this sort of thing at the moment (amplifying DNA in vectors, making recombinant DNA etc.) and it takes so long to do each step. Still, like you say, once someone does it all that has to be done is grow up cultures of bacteria to make these drugs.

Would this be possible though. I thought that certain cellular elements had to be present to make particles like salvinorin. I don't know much about it but salvinorin isn't made up of ammino acids is it? I would have thought that this would mean that after DNA in the plant cells is transcribed and translated to a protein, that the protein would act as an enzyme for the production of salvinorin A.

Now if you incorporate a recombinant plasmid into an E. Coli it will make the proteins, but they wouldn't be able to do anything unless the right molecules were in the cell to make salvinorin.

Like I say, i'm only a second year biochemist so i don't really know THAT much about it, still, i find the whole concept pretty interesting.

[Teonanacatl]

Yeah...from my own mere undergraduate understanding, encoding the genes for the enzymes involved in the path is just that, encoding for the enzymes (I do have a point...).
Basically then, you just need to either
a) supply the precursor required for the production of salvinorin or
b) encode for enzymes further back down the path...
now I do know that salvinorin A is a diterpenoid (unfortunately, shikimates are my forte...mevalonate pathway is still pretty new to me). However, all the diterpenes (basically just means C20) result from chemical modifications to geranylgeranyl diphosphat (GGPP), so the ultimate goal I am guessing would be to encode for all the enzymes involved in the pathway from GGPP to salvinorin A...that said, I can't help much more than that yet as I don't know the biosynthetic route involved in neoclerodane diterpene formation...

[LaBTop]

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