ejlmp (Junior Member)
04-21-00 21:45
No 127141
       Psilocin in 5 steps  Bookmark   

I just came across a 1998 paper in Heterocycles, 49, 451-457 (1998)
on a 5 step synthesis of psilocin from indole-3-carbaldehyde
(indole-3-carboxaldehyde, available from Aldrich
 http://www.sigma-aldrich.com  at 25g for $53.20, S/N 12,944-5).
The authors (Yamada, Tamura and Somei, M*) carry out a one pot rxn
using indole-3-carbaldehyde and Tl(OCOCF3)3 in TFA at rt. for 24 h. Next step
they add iodine, CuI in DMF at rt. for 1h. The third step of this one pot involves
adding KH and benzyl alc. to give after silica gel column (1:1 EtOAc-hex.) 72% yield of 4-benzyloxyindole-3-carbaldehyde. The first step involves regioselective thallation at the
4 position. The C-Tl bond is converted to the C-I at 4 and this 4-iodoindole compound is protected in the last step. This was converted to 4-benzyloxyindole-3-acetonitrile in 89% yield
using NaBH4 in presence of NaCN in MeOH and formamide. LAH reduction in ether follows to give 96% yield of  4-benzyloxyTryptamine. If they used THF, the yield fell to 25-46%.  Next dimethylation with HCHO and NaCNBH4 in HOAc gave 97% yield.
Removal of protection at position 4 with 10% Pd/C and hydrogenation gave psilocin in
84% yield (note that all yields are of purified product). Overall yield is 50%.
Thought you might be interested. I'm not aware that this work has been discussed in the
Back alleys of drug chemistry.
Eric
Pet your dog instead: http://home.earthlink.net/~ejlmp/Maggie.html
We made it through another day Maggie
and we found somethinŐ out. 		 
 
 
 
    Rhodium
(Administrator)
04-22-00 09:31
No 127142
       Re: Psilocin in 5 steps  Bookmark   

Argh! Thallium compounds are extraordinary toxic, and I wouldn't reccommend this method.  There are better ways involving 4-oxo-tetrahydroindole. 		 
 
 
 
    ejlmp
(Junior Member)
04-23-00 01:46
No 127144
       Re: Psilocin in 5 steps
(Rated as: excellent) 		 Bookmark   

The 4-benzyloxy-DMT can be converted to the o-acetyl psilocin (stable and consumable)  by hydrogenation (10%Pd/C) with NaOAc in benzene according Nichols and Fescas (see Synthesis, no. 6, p935-938, 1999). The paper also gives recipe to psilocybin. This overall route starts from the 4-benzyloxyindole.
Eric
Pet your dog instead: http://home.earthlink.net/~ejlmp/Maggie.html
 
 
 
 
    ejlmp
(Junior Member)
04-23-00 12:31
No 127143
       Re: Psilocin in 5 steps  Bookmark   

I knew there would be some squawks about the thallium, but hey, what are you
going to do when you have to use tert-butyl lithium sometime? ItŐs a tough place sometimes.
BTW, if you want to go to the full paper on Psilocin with formulas, go to http://argon.ch.ic.ac.uk/ectoc/echet98/pub/039/index.htm.  The authors are making  other derivatives on the benzene ring.
Eric
Pet your dog instead: http://home.earthlink.net/~ejlmp/Maggie.html