THE ENANTIOSPECIFIC SYNTHESIS OF AN ISOXAZOLINE - A RGD MIMIC PLATELET GPIIB IIIA ANTAGONIST/

A convergent, large-scale, chiral synthesis of isoxazoline 1 has been achieved in 37% overall yield and >99.6% optical purity, starting From L-asparagine and 4-cyanobenzaldehyde. Hofmann reaction of N-alpha-n-B oc-L-asparagine with iodosobenzene diacetate provides optically pure N -alpha-Boc-L-alpha,beta-diaminopropionic acid (8) in 75% yield. A proc ess of lipase resolution-base catalyzed epimerization gives the single enantiomer 5. Reaction of acid 5 with amine 9 in the presence of thio nyl chloride forms the framework of 1. A Pinner reaction of intermedia te 4 in methyl acetate or anisole, followed by an amidination with amm onium acetate, gives optically pure product 1.