Chiral Synthesis of Pyrrolidine Core Compounds en route to Neuronal Nitric Oxide Synthase Inhibitors

摘要

A chiral synthesis of pyrrolidine compounds en route to selective neuronal nitric oxide synthase inhibitors, and representative inhibitor compounds heretofore unattainable.

主权项

1. A method of preparing a chiral pyrrolidine core compound, said method comprising:
providing an N-Boc-protected pyrrolidine-3,4-epoxide; alkylating said epoxide with an N-Boc-protected, amino-substituted haloalkylheterocyclic compound, said alkylation providing a racemic alkyl-substituted trans-pyrrolidine alcohol; protecting said amino group on said heterocyclic substituent with a Boc reagent; resolving said racemic trans-alcohol by camphanic acid esterification, to provide separable diastereomers; and hydrolysis of one said enantiomer of said racemate, to provide a chiral 4-hydroxypyrrolidine compound.