1. Stereocontrolled Synthesis of syn-β-Hydroxy-α-Amino Acids by Direct Aldolization of Pseudoephenamine Glycinamide.
- Author
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Seiple, Ian B., Mercer, Jaron A. M., Sussman, Robin J., Zhang, Ziyang, and Myers, Andrew G.
- Subjects
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AMINO acid synthesis , *STEREOCHEMISTRY , *ALDOL condensation , *GLYCINAMIDE , *HYDROLYSIS , *PHARMACEUTICAL chemistry - Abstract
β-Hydroxy-α-amino acids figure prominently as chiral building blocks in chemical synthesis and serve as precursors to numerous important medicines. Reported herein is a method for the synthesis of β-hydroxy-α-amino acid derivatives by aldolization of pseudoephenamine glycinamide, which can be prepared from pseudoephenamine in a one-flask protocol. Enolization of ( R, R)- or ( S, S)-pseudoephenamine glycinamide with lithium hexamethyldisilazide in the presence of LiCl followed by addition of an aldehyde or ketone substrate affords aldol addition products that are stereochemically homologous with L- or D-threonine, respectively. These products, which are typically solids, can be obtained in stereoisomerically pure form in yields of 55-98 %, and are readily transformed into β-hydroxy-α-amino acids by mild hydrolysis or into 2-amino-1,3-diols by reduction with sodium borohydride. This new chemistry greatly facilitates the construction of novel antibiotics of several different classes. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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