Remarkable diastereomeric rearrangement of an alpha-acyloxy beta-ketosulfide to an alpha-acyloxy thioester: a novel approach to the synthesis of optically active (2S,3S) beta-amino alpha-hydroxy acids.
[reaction: see text] A novel and efficient synthetic method is described for (2S,3S)-3-amino-2-hydroxy-4-phenyl butyric acid derivatives, which are useful intermediates of enzyme inhibitors. This involves a Pummerer rearrangement of a beta-ketosulfoxide derived from l-phenylalanine followed by highly stereoselective acyl migration. From these studies, it appears that nitrogen-protecting groups exert a substantial influence over stereoselectivity. The mechanism of the rearrangement is discussed. beta-Amino alpha-hydroxy carboxylic acids are important pharmaceutical intermediates, and this method may provide a versatile synthesis from various amino acids in a few steps.
Suzuki
Takayuki
T
AminoScience Laboratories, Ajinomoto Co., Inc. 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-8681, Japan.
Honda
Yutaka
Y
Izawa
Kunisuke
K
Williams
Robert M
RM
D017320:HIV Protease Inhibitors / Q000138:chemical synthesis*; D008968:Molecular Conformation; D010654:Phenylbutyrates / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013440:Sulfides
D017320:HIV Protease Inhibitors; D010654:Phenylbutyrates; D013440:Sulfides; C034940:3-amino-2-hydroxy-4-phenylbutanoic acid