Asymmetric synthesis of a cyclopropanecarboxylic acid derivative – the potential agonist/antagonist of GABA receptors

Abstract

The synthesis of enantiomerically pure (1S,2S,S_P)-1-[hydroxy(methyl)phosphonyl]-2-aminocyclopropanecarboxylic acid (1) (a potential agonist/antagonist of GABA receptors) was accomplished in six steps based on optically inactive methyl 2-[methoxy(methyl)phosphonyl]acrylate (2). The key steps of this synthesis included the cyclopropane ring formation by the asymmetric cyclopropanation reaction of 2 with (S)-dimethylsulfonium(p-tolylsulfinyl)methylide (3), regio and stereoselective installation of ethoxycarbonyl group in the cyclopropane ring, and the chemoselective desulfinylation reaction conducted with phenylsilane under the basic conditions.

Graphical Abstract

Keywords:

• Cyclopropanes
• ylides
• amino acids
• cyclopropyl sulfoxide
• asymmetric synthesis

Acknowledgments

CCDC deposition 2116101 contains the supplementary crystallographic data for 8a. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/structures/, or by e-mailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone].

Disclosure statement

No potential conflict of interest was reported by the authors.

Dedication

This work is dedicated to the memory of Associate Professor Wanda Halina Midura (07.01.2019), our mentor, teacher and friend.

Additional information

Funding

The authors acknowledge financial support through National Science Grant No. DEC-2017/01/X/ST5/01911 (for A. R.).