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.
Department of Biochemistry, Queen Mary and Westfield College, University of London, UK.
E P
EP
Hagi-Pavli
C S
CS
Simms
E L
EL
Ostler
K
K
Brocklehurst
G
G
Gallacher
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