The Enantioselective Synthesis of β‐Amino Acids, their α‐hydroxy derivatives, and the <i>N</i>‐terminal components of bestatin and microginin

AbstractL‐Aspartic acid by tosylation, anhydride formation, and reduction with NaBH4 was converted into (3S)‐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 (3R)‐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 (2S, 3R)‐3‐amino‐2‐hydroxybutanoic acids 24 including the N‐terminal acids 24e ( =3) and 24f ( =4) of bestatin and microginin (de > 95%), respectively.

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