Christopher W. Doecke

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.

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.

Ortho-hydroxyl assisted deoxygenation of phenones. Regiochemical control in the synthesis of monoprotected resorcinols and related polyphenolic hydroxyl systems

A method for the selective protection of polyphenolic hydroxyls is described. This approach relies on the deoxygenation of a benzylic ketone ortho to at least one of the phenolic hydroxyl groups.

The use of N,O-bis(tert-butoxycarbonyl)-hydroxylamine in the synthesis of N-hydroxylamines and hydroxamic acids

Abstract N,O-bis ( tert -butoxycarbonyl)-hydroxylamine has been used in the synthesis of 5-lipoxygenase inhibitor LY280810. In addition, this reagent has been utilized to synthesize a number of other hydroxylamine and hydroxamic acid derivatives in high yields.