THIAZOLE-BASED STEREOSELECTIVE ROUTES TO LEUCINE AND PHENYLALANINE HYDROXYETHYLENE DIPEPTIDE ISOSTERE INHIBITORS OF RENIN AND HIV-1 ASPARTIC PROTEASE

A new synthesis of hydroxyethylene dipeptide isosteres for Leu-Leu and Phe-Phe in their gamma-lactone form 1a and 1b employing beta-amino-al pha-hydroxy aldehydes with singly and doubly protected nitrogen has be en developed. These key intermediates, which are available through the thiazole-aldehyde synthesis from L-leucine and L-phenylalanine, were converted to alkanoates by Wittig olefination and reduction of the eth ylenic double bond. Lactonization and stereoselective alkylation at C- 2 of the resulting lactones completed the building up of the structura l framework. Overall yields were in the range 16-19% for 1a and 22-23% for 1b.