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

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.