Asymmetric synthesis of the (S)-1,1-dioxido-isothiazolidin-3-one phosphotyrosine mimetic via reduction of a homochiral (R)-oxido-isothiazolidin-3-one

Andrew P Combs; Brian Glass; Laurine G Galya; Mei Li

doi:10.1021/ol0701262

Asymmetric synthesis of the (S)-1,1-dioxido-isothiazolidin-3-one phosphotyrosine mimetic via reduction of a homochiral (R)-oxido-isothiazolidin-3-one

Org Lett. 2007 Mar 29;9(7):1279-82. doi: 10.1021/ol0701262. Epub 2007 Mar 6.

Authors

Andrew P Combs¹, Brian Glass, Laurine G Galya, Mei Li

Affiliation

¹ Discovery Chemistry, Experimental Station, Incyte Corporation, Wilmington, DE 19880, USA. [email protected]

PMID: 17338536
DOI: 10.1021/ol0701262

Abstract

[structure: see text]. The first asymmetric synthesis of the (S)-1,1-dioxido-isothiazolidin-3-one ((S)-IZD) pTyr mimetic, which has been incorporated into the recently reported potent protein tyrosine phosphatase 1B (PTP1B) inhibitors, is presented herein. The key reaction is the reduction of the (R)-oxido-isothiazolidin-3-one heterocycle with excellent regiochemical and stereochemical control (>98% ee; 82% yield).

MeSH terms

Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Models, Molecular
Molecular Mimicry
Molecular Structure
Phosphotyrosine / chemistry*
Protein Tyrosine Phosphatases / antagonists & inhibitors
Stereoisomerism
Thiazoles / chemical synthesis*
Thiazoles / chemistry
Thiazoles / pharmacology

Substances

Enzyme Inhibitors
Thiazoles
isothiazolidinone
Phosphotyrosine
Protein Tyrosine Phosphatases