The Open Organic Chemistry Journal

2009, 3 : 22-34
Published online 2009 January 26. DOI: 10.2174/1874095200903010022
Publisher ID: TOOCJ-3-22

Chemoenzymatic Synthesis of α-Substituted Serines Enantiodivergent Transformation

Shigeki Sano , Michiyasu Nakao , Masanori Takeyasu , Chiyo Yamamoto , Syuji Kitaike , Yasuko Yoshioka and Yoshimitsu Nagao
Graduate School of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan

ABSTRACT

A series of (R)-N-Cbz-2-alkyl-2-amino-3-hydroxypropyl acetates was prepared by enzymatic acetylation of NCbz- 2-alkyl-2-aminopropane-1,3-diols with immobilized lipoprotein lipase from Pseudomonas sp. in up to 98% enantiomeric excess (ee). Enantiodivergent oxidation of (R)-N-Cbz-2-alkyl-2-amino-3-hydroxypropyl acetates readily furnished (R)- and (S)-α-substituted serines (α-benzylserines and α-methylserines). Enzymatic hydrolysis of diethyl N-Cbz-2- amino-2-methylmalonate catalyzed by porcine liver esterase afforded (R)-N-Cbz-2-amino-3-ethoxy-2-methyl-3- oxopropanoic acid in 97% ee. (R)-N-Cbz-2-amino-3-ethoxy-2-methyl-3-oxopropanoic acid was also transformed to both enantiomers of α-methylserine via enantiodivergent reduction.

Keywords:

Asymmetric, synthesis, Lipoprotein lipase, Acetylation, 1,3-Diols, Enantiodivergent, a-Substituted serines.