Chemo-enzymatic synthesis of (S)-(+)-cericlamine and related enantiomerically pure 2,2-disubstituted-2-aminoethanols

Abstract

The synthesis of (S)-(+)-cericlamine (S)-1 and related disubstituted amino alcohols is described as an example of the stereoselective synthesis of amino alcohols from disubstituted amino acids and their corresponding amides. Thus, the amino alcohols (S)-1, (R)-6 and (S)-7 are prepared from enantiomerically pure α-methyl-3,4-dichlorophenylalanine (amide), (R)-4 and (S)-5, respectively, by application of the recently developed sodium–propan-1-ol or NaBH₄–H₂SO₄ reduction method followed by reductive alkylation. (R)-4 and (S)-5 were prepared by phase transfer catalysis and subsequent enzymatic hydrolysis of racemic 4 using an amidase from Ochrobactrum anthropi.