Synthesis 2019; 51(24): 4568-4575
DOI: 10.1055/s-0039-1690705
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© Georg Thieme Verlag Stuttgart · New York

Stereoselective Synthesis of syn-γ-Hydroxynorvaline and Related α-Amino Acids

Dominika Valachová
a  Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia   Email: pavol.jakubec@stuba.sk
,
Branislav Ferko
a  Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia   Email: pavol.jakubec@stuba.sk
,
Eva Puchľová
a  Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia   Email: pavol.jakubec@stuba.sk
,
Oľga Caletková
a  Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia   Email: pavol.jakubec@stuba.sk
,
Dušan Berkeš
a  Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia   Email: pavol.jakubec@stuba.sk
,
Andrej Kolarovič
b  Department of Chemistry, Faculty of Education, Trnava University, Priemyselná 4, 91843 Trnava, Slovakia
,
a  Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia   Email: pavol.jakubec@stuba.sk
› Author Affiliations
This work was supported by the Agentúra na Podporu Výskumu a Vývoja (Slovak Research and Development Agency) under contract no. APVV-16-0258.
Further Information

Publication History

Received: 09 August 2019

Accepted after revision: 17 September 2019

Publication Date:
16 October 2019 (online)

Abstract

The total syntheses of three enantiomerically pure non-proteinogenic amino acids, l-norvaline, γ-oxonorvaline, and syn-γ-hydroxynorvaline, are reported. The chromatography-free route pivoted on the construction of highly enantiomerically enriched substituted α-amino-γ-oxopentanoic acid, from which all three members were accessed divergently via chemoselective and stereoselective reductions. The rapid synthesis of this key α-amino-γ-oxopentanoic acid was achieved by a highly diastereoselective crystallisation-driven three-component Mannich reaction from the readily available building blocks acetone, glyoxylic acid monohydrate, and (S)-(4-methoxyphenyl)ethylamine. The enantiomeric purity of all target molecules was confirmed by HPLC analysis, either of the amino acids or their derivatives.

Supporting Information

 
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