Synthesis of a new sulfur-containing dipeptide analogue

✍ Scribed by J.Olle Karlsson; Anita Lundblad; Bengt Malm; Ingemar Nilsson; Toivo Nitenberg; Ingemar Starke; Henrik Sörensen; Christer Westerlund

• Book ID: 104229242
• Publisher: Elsevier Science
• Year: 1989
• Tongue: French
• Weight: 200 KB
• Volume: 30
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)99090-7

✦ Synopsis

The synthesis of a sulfur-containing Cha-Ala isostere is reported (Cha = cyclohexylalanine). The diastereoconversion of a N-2-Boc-amino alcohol has been achieved by treatment with methanesulfonyl chloride in pyridine resulting in the corresponding oxazolidin-a-one with inverted stereochemistry at the carbinol carbon.

Dipeptide analogues are currently the subject of much interest both in the pharmaceutical industry and in academial. This is warranted by the potential for obtaining therapeutically active drugs by incorporating these moieties in transition state analogues' and metabolically stable peptides3. Our interest in this field derives from our involvement in the search for orally active renin inhibitors. Based on structure-activity relationships, short Cha-Ala derived isosteres were considered to be of interest4. We now wish to report the synthesis of one such sulfur-containing replacement, 8.