The Enantioselective Synthesis of β-Amino Acids, their α-hydroxy derivatives, and the N-terminal components of bestatin and microginin

✍ Scribed by Charles W. Jefford; James McNulty; Zhi-Hui Lu; Jian Bo Wang

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: German
• Weight: 1016 KB
• Volume: 79
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19960790426

✦ Synopsis

Abstract

L‐Aspartic acid by tosylation, anhydride formation, and reduction with NaBH~4~ was converted into (3__S__)‐3‐(tosylamino)butan‐4‐olide (8; Scheme 1). Tretment of 8 with ethanolic trimethylsilyl iodide gave the N‐protected deoxy‐iodo‐β‐homoserine ethyl ester 9. The latter, on successive nucleophilic displacement with lithium dialkyl‐cuprates ( → 10a–e), alkaline hydrolysis ( → 11a–e), and reductive removal of the tosyl group, produced the corresponding 4‐substituted (3__R__)‐3‐aminobutanoic acids 12a–e (ee > 99%). Electrophilic hydroxylation of 8 ( → 19; Scheme 3), subsequent iodo‐esterification ( → 21; Scheme 4), and nucleophilic alkylation and phenylation afforded, after saponification and deprotection, a series of 4‐substituted (2__S__, 3__R__)‐3‐amino‐2‐hydroxybutanoic acids 24 including the N‐terminal acids 24e ( =3) and 24f ( =4) of bestatin and microginin (de > 95%), respectively.