Regio- and diastereoselective construction of α-hydroxy-δ-amino ester derivatives via 1,4-conjugate addition of β,γ-unsaturated N-sulfonylimines

Lin Qiu; Lixin Gao; Jixing Tang; Dongwei Wang; Xin Guo; Shunying Liu; Liping Yang; Jia Li; Wenhao Hu

doi:10.1021/jo500176g

Regio- and diastereoselective construction of α-hydroxy-δ-amino ester derivatives via 1,4-conjugate addition of β,γ-unsaturated N-sulfonylimines

J Org Chem. 2014 May 2;79(9):4142-7. doi: 10.1021/jo500176g. Epub 2014 Apr 15.

Authors

Lin Qiu¹, Lixin Gao, Jixing Tang, Dongwei Wang, Xin Guo, Shunying Liu, Liping Yang, Jia Li, Wenhao Hu

Affiliation

¹ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Department of Chemistry, East China Normal University , Shanghai, 200062, China.

PMID: 24689439
DOI: 10.1021/jo500176g

Abstract

A first example of 1,4-conjugate addition of β,γ-unsaturated N-sulfonylimines via the oxonium ylides trapping process was developed. This method afforded a novel and efficient access for the high regio- and diastereoselective construction of α-hydroxyl-δ-amino esters derivatives, which exhibit inhibitory activity on PTP1B and SIRT1 enzymes in vitro. The synthetic potentials and the biological activity of the resulting products were well demonstrated to be promising for drug discovery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Esters
Imines / chemistry*
Molecular Structure
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Sirtuin 1 / antagonists & inhibitors*
Sirtuin 1 / metabolism
Stereoisomerism
Structure-Activity Relationship
Sulfones / chemistry*

Substances

Enzyme Inhibitors
Esters
Imines
N-sulfonylimine
Sulfones
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1
SIRT1 protein, human
Sirtuin 1