Michael J. Genin

An improved method of oxazolidinone hydrolysis in the asymmetric synthesis of α-alkylprolines

Abstract An improvement in Seebachs method for the synthesis of α-alkylprolines is reported wherein the hydrolysis of the chiral oxazolidinone 2 is performed on a suspension of silica gel in MeOH/H 2 O. Following hydrolysis, the pure α-alkylproline can be obtained by filtration thereby avoiding a tedious ion exchange purification.

Design and synthesis of a conformationally constrained analog of the bis(heteroaryl)piperazine (BHAP) HIV-1 reverse transcriptase inhibitor atevirdine

Abstract The design and synthesis of a novel conformationally constrained spiro analog of the BHAP class of HIV-1 reverse transcriptase inhibitors, based on the molecular modeling and the X-ray crystal structure of the clinical candidate atevirdine, is described.

Imidazopyridine and Pyrazolopiperidine Derivatives as Novel Inhibitors of Serine Palmitoyl Transferase

To develop novel treatments for type 2 diabetes and dyslipidemia, we pursued inhibitors of serine palmitoyl transferase (SPT). To this end compounds 1 and 2 were developed as potent SPT inhibitors in vitro. 1 and 2 reduce plasma ceramides in rodents, have a slight trend toward enhanced insulin sensitization in DIO mice, and reduce triglycerides and raise HDL in cholesterol/cholic acid fed rats. Unfortunately these molecules cause a gastric enteropathy after chronic dosing in rats.

A novel method for the t-butylation of aromatic amines

Abstract A new method for the synthesis of t -butylamines from amines in two steps via α-aminonitriles, and its application to various arylamines is discussed.