Addition of Allylic Metals to α-Aminoaldehydes. Application to the Synthesis of Statine, Ketomethylene and Hydroxyethylene Dipeptide Isosteres

✍ Scribed by J.V.N. Vara Prasad; Daniel H. Rich

• Publisher: Elsevier Science
• Year: 1990
• Tongue: French
• Weight: 170 KB
• Volume: 31
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)98790-2

✦ Synopsis

A general and stereoselective method to statine, ketomethylene and hydroxyethylene dipeptide isosteres is described. The key reaction is the diastereoselective allyl metal addition to c~-aminoaldehydes.

Many potent inhibitors of proteolytic enzymes1 have been designed by replacing the scissile amide bond in a substrate with a hydrolytically stable functionality, such as the statine or ketomethylene and hydroxyethylene isosteres.2 Numerous synthetic methods to make these important isosteres have been reported,3.4 but many are not sufficiently general and stereoselective, or else use chiral auxiliaries to achieve good stereoselection. New methods to synthesize these isosteres are needed since these are used to prepare potent inhibitors of therapeutically important aspartic proteinases,1 e.g. HIV protease.S We report herein a stereoselective synthesis of a key intermediate that can be used to prepare statine and its