John P. Gardner

An enantioselective synthesis of loracarbef (LY163892/KT3777)

Abstract An enantioselective synthesis of the new, orally absorbable, totally synthetic β-lactam antibiotic, loracarbef (LY163892/KT3777) is described.

Synthesis of carbacephem antibiotics: synthesis via dieckmann reaction using phenyl esters to direct the regioselectivity of the cyclization

Abstract β-Ketoesters useful for elaboration to carbacephems were synthesized from a variety of enantiomerically pure diesters. Use of phenyl esters to direct the regioselectivity was demonstrated.

Enantioselective Syntheses of 1-Carbacephalosporins from Chemoenzymically Derived β-Hydroxy-α-Amino Acids: Applications to the Total Synthesis of Carbacephem Antibiotic Loracarbef

Abstract Serine hydroxymethyltransferase (SHMT) derived from recombinant E. coli was found to be able to catalyze the condensation between glycine and 4-pentenaldehyde, affording enantiopure l -erythro-2-amino-3-hydroxy-6-heptenoic acid (AHHA) in high yield and throughput. Conversion of this chiral intermediate of biosynthetic origin to the oral carbacephalosporin antibiotic loracarbef (Lorabid®) via β-lactam forming reactions and subsequent Dieckmann cyclization was achieved.

Enantioselective synthesis of the carbacephem antibiotic loracarbef via Mitsunobu and Dieckmann cyclization from an unnatural amino acid

The nucleus of the carbacephem antibiotic loracarbef was synthesized in a highly efficient and enantioselective fashion from 2S,3S-2-amino-3-hydroxy-6-heptenoic acid (AHHA), which was derived from enzyme-catalyzed condensation of glycine and 4-pentenaldehyde. The bicyclic framework of this compound was established through sequential Mitsunobu reaction and aldol condensations.