A PRACTICAL TOTAL SYNTHESIS OF COCAINE'S ENANTIOMERS. JOHN F CASALE.

Forensic Science International, issue thirty three.1987, pages 275 to 298.Show more

A PRACTICAL TOTAL SYNTHESIS OF COCAINE'S ENANTIOMERS.
JOHN F CASALE.
State Bureau of Investigation.
Accepted December tenth, 1980.
Summary.
A simplified total synthesis of the single enantiomers of cocaine and racemic cocaine is outlined. The synthesis employs common laboratory glassware, reagents, and methods which can be performed in most forensic laboratories. The procedure for the isolation and purification of the dextrorotatory enantiomer of cocaine is presented.
Key words: Cocaine; Enantiomers; Total synthesis.
Introduction.
In many jurisdictions cocaine is listed as a controlled substance under statutes covering coca leaves and their extracts. Therefore only the levorotatory isomer of cocaine would be controlled. These laws do not include optical isomers and dia-stereoisomers. The question of enantiomeric composition has recently become popular with defense attorneys. Minus Cocaine is the naturally occurring alkaloid extracted from coca leaves. Racemic and Plus cocaine can only be obtained through a chemical synthesis.
The molecular structure of cocaine was first described by Willstatter and Muller, reference one in 1898. It was not until the early 1950's that the principles and methodologies of stereochemistry were applied to cocaine's tropane ring skeleton. Findlay, reference two, Fodor reference three four, and others established the stereochemistry of the tropane alcohols and their esters. Once this groundwork was laid, the three-dimensional structures of cocaine and its dia-stereoisomers, pseudo-cocaine, alloco-caine, and allo-pseudo-cocaine, were elucidated by Findlay references five to seven and Hardegger et at, reference eight. Findlay's three-dimensional structures were confirmed in 1968 by Sinnema et at reference nine using NMR spectral analysis. Electron impact fragmentation patterns of the tropane alkaloids were later established by Blossey et al. reference ten. These workers identified the major mass spectral fragmentation patterns by deuterium and substituent labelling.
Fragmentation patterns for various tropinone analogs have also been determined by Kashman and Cherkez, reference eleven.