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J Org Chem. 2011 Dec 2;76(23):9785-91. doi: 10.1021/jo2018679. Epub 2011 Nov 9.

Chemoenzymatic synthesis of each enantiomer of orthogonally protected 4,4-difluoroglutamic acid: a candidate monomer for chiral Brønsted acid peptide-based catalysts.

Author information

1
Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA.

Abstract

We have accomplished an asymmetric synthesis of each enantiomer of 4,4-difluoroglutamic acid. This α-amino acid has been of interest in medicinal chemistry circles. Key features of the synthesis include highly scalable procedures, a Reformatsky-based coupling reaction, and straightforward functional group manipulations to make the parent amino acid. Enantioenrichment derives from an enzymatic resolution of the synthetic material. Conversion of the optically enriched compounds to orthogonally protected forms allows for the selective formation of peptide bonds. 4,4-Difluoroglutamic acid, in a suitably protected form, is also shown to exhibit enhanced catalytic activity in both an oxidation reaction and a reduction reaction, in comparison to the analogous glutamic acid derivative.

PMID:
22039908
PMCID:
PMC3228520
DOI:
10.1021/jo2018679
[Indexed for MEDLINE]
Free PMC Article

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