Synthesis of a transition state analogue for the hydrolysis of cocaine: assistance to phosphonylation of a 3beta-hydroxytropane by a neighbouring amide group.
A simple synthesis of phenylphosphonate monoester analogues of the transition state for hydrolysis of the benzoyl ester group in cocaine is provided by the reaction of 2beta-amido-3beta-tropanols with phenylphosphonyl dichloride. Steric hindrance to phosphonylation of the hydroxyl is overcome because the neighbouring 2beta-amido group participates in the reaction. The intramolecular assistance by the amide to formation of the phosphonate ester is influenced by the electronic environment of the amide group.
Hagi-Pavli
E P
EP
Department of Biochemistry, Queen Mary and Westfield College, University of London, UK.
Simms
C S
CS
Ostler
E L
EL
Brocklehurst
K
K
Gallacher
G
G
D000577:Amides / Q000737:chemistry*; D003042:Cocaine / Q000737:chemistry*; D006868:Hydrolysis; D063065:Organophosphonates / Q000737:chemistry*; D013997:Time Factors; D014326:Tropanes / Q000737:chemistry
D000577:Amides; D063065:Organophosphonates; D014326:Tropanes; D003042:Cocaine