Synthesis of Cocaine analogs from Arecoline
This is one of the most promising area of research on cocaine analogs that I’ve come across. In the article [1], the authors were attempting to come up with an equivalent of methadone for cocaine addicts. That is, a substance that would have some of the effects of cocaine without all the euphoria (Coke-Lite®, I guess it will be called). The research was based on some work done in 1973 (by Clarke [2]) in which a series of similar compounds was made and found not to cause stimulation in mice (i.e. no fun). However, in this study, the compounds were found to be up to 30 times the potency of cocaine in blocking dopamine transport or binding of cocaine to its receptor. So the results are rather confusing. Possibly the researchers have actually found a lead in their search for coke-adone, or maybe they have found a series of ridiculously easy to synthesize highly potent coke analogs. Either way, interesting work. Currently they are shooting up monkeys to see if they like it or not, but it may be years before they publish their work. Maybe someone out there could help them out. I always say, never send a monkey to do a man’s work.
In Clarke’s 1973 paper [2], a series of structurally reduced cocaine analogs are synthesized in which 2 carbons and an ester group have been removed from the tropane skeleton, giving 4-phenyl-piperidines with an ester group at the 3-position. The most active compound in their series is about 30 times the potency of cocaine (in blocking dopamine uptake). The synthesis is much easier than any other active cocaine analog, and starts from non-exotic reagents.
The main starting material used by the authors is Arecoline (3,4-unsaturated N-methyl-piperidine-3-carboxylic acid methyl ester), the active principle of the popular red betel nut. Treatment of this alpha,beta-unsaturated ester with the Grignard reagent 4-Chlorophenylmagnesium Bromide gave rise to four products, easily grouped into two racemic forms of each cis- and trans- isomer. The racemic cis-isomer is twice as potent as cocaine, while the racemic trans-isomer is only half as strong.
The authors start with arecoline (the active compound in betel nut: N-methyl-piperidine- 3-carboxylic acid methyl ester with a double bond between the 3 and 4 positions). Reaction of this with a 4-chlorophenylmagnesium bromide grignard reagent gives a mixture of a total of four discrete entities: A cis- and trans-mixture in a 3:1 ratio, each constisting of a of two isomers, each isomer also being racemic, all which the which the authors resolve through fractional crystallization as their dibenzoyl tartaric acids, but this is not strictly necessary since each of the isomers are active. Arecoline Hydrobromide is a fairly cheap commercial starting material, $80/50g from Aldrich. Also, I think that it is used in veterinary medicine.
source http://www.erowid.org/archive/rhodium/chemistry/cocaine.analog.arecoline.html
ok check this out
Arecoline hydrobromide
VETRANALâ„¢, analytical standard
DOWNLOAD MSDS (PDF)
Synonym: 1-Methyl-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid methyl ester hydrobromide, Arecaidine methyl ester hydrobromide, Methyl 1,2,5,6-tetrahydro-1-methyl-3-pyridinecarboxylate hydrobromide, Methyl 1-methyl-1,2,5,6-tetrahydronicotinate hydrobromide
CAS Number 300-08-3 Empirical Formula (Hill Notation) C8H13NO2 · HBr Molecular Weight 236.11 Beilstein Registry Number 3914826 EC Number 206-087-3 MDL number MFCD00039041 PubChem Substance ID 24869721
http://www.sigmaaldrich.com/catalog/product/fluka/31593?lang=en®ion=US
:cokesniff
It feels good to be running from the devil
Another breath and I'm up another level
It feels good to be up above the clouds
It feels good for the first time in a long time now