Determination of the absolute configuration of two αvβ6 integrin inhibitors for the treatment of idiopathic pulmonary fibrosis and investigations on the asymmetric 1,4-addition of arylboronic acids to crotonate esters bearing a C4-oxygen substituent |
| |
Authors: | Panayiotis A Procopiou Tim N Barrett Royston CB Copley Christopher J Tame |
| |
Institution: | 1. Medicinal Chemistry, Fibrosis and Lung Injury DPU, Respiratory Therapeutic Area, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom;2. Platform Technology & Science, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom |
| |
Abstract: | The absolute configuration of two novel αvβ6 integrin inhibitors was established via degradation to the corresponding C3-aryl substituted butyrolactone. The configuration of the resulting lactones was established by asymmetric synthesis using 1,4-addition of arylboronic acids to butenolide, catalysed by bis(norbornadiene)rhodium (I) tetrafluoroborate in the presence of (R)-BINAP, and confirmed by X-ray crystallography. Studies on arylboronic acid conjugate additions to acyclic crotonate esters bearing a γ-oxygen substituent are also reported. Three Rh catalysts were investigated and the one giving the highest enantioselectivity was bis(norbornadiene)rhodium (I) tetrafluoroborate. |
| |
Keywords: | Corresponding author Tel : +44 1438 790496 fax: +44 1438 768302 |
本文献已被 ScienceDirect 等数据库收录! |
|