Synthesis of Optically Active, Ring-Substituted N-Benzyloxycarbonylphenylalanines via 2-Benzyloxycarbonylamino-2-arylalkylmalonates

✍ Scribed by Hans Rudolf Bosshard; Arieh Berger

• Publisher: John Wiley and Sons
• Year: 1973
• Tongue: German
• Weight: 557 KB
• Volume: 56
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19730560603

✦ Synopsis

Abstract

Diethyl or dimethyl benzyloxycarbonylaminomalonate was reacted with ring substituted benzyl halides and the resulting arylalkyl derivatives (3 to 6) half‐saponified to the DL‐monoacid‐monoesters (7 to 10). Decarboxylation by refluxing in dioxane afforded the N‐benzyl oxycarbonyl‐DL‐amino acid esters (11 to 14), which were resolved into their optical antipodes by enzymic hydrolysis of the ester group with Subtilisin, type Carlsberg. Enzymic hydrolysis led to the N‐benzyloxycarbonyl‐L‐amino acids (15 to 18) and to the corresponding D‐amino acid esters. The latter were converted to the N‐benzyloxycarbonyl‐D‐amino acids (19 and 20) by alkaline hydrolysis of the ester groups. These derivatives could be used directly for further peptide synthesis. The following compounds were prepared: N‐benzyloxycarbonyl derivatives of p‐methyl‐L‐phenylalanine (15), p‐methyl‐D‐phenylalanine (19), p‐fluoro‐L‐phenylalanine (16), m‐fluoro‐L‐phenylalanine (17), m‐fluoro‐D‐phenylalanine (20) and penta‐fluoro‐L‐phenylalanine (18). The free amino acids were obtained by removal of the benzyloxycarbonyl group with HBr in acetic acid.