Asymmetric synthesis of the (S)-1,1-dioxido-isothiazolidin-3-one phosphotyrosine mimetic via reduction of a homochiral (R)-oxido-isothiazolidin-3-one.
[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).
Combs
Andrew P
AP
Discovery Chemistry, Experimental Station, Incyte Corporation, Wilmington, DE 19880, USA. acombs@incyte.com
Glass
Brian
B
Galya
Laurine G
LG
Li
Mei
M
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D019000:Phosphotyrosine / Q000737:chemistry*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013844:Thiazoles; C512915:isothiazolidinone; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases