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

Q2 Chemistry

Tetrahedron, asymmetry Pub Date : 2017-10-15 DOI:10.1016/j.tetasy.2017.08.017

Panayiotis A. Procopiou , Tim N. Barrett , Royston C.B. Copley , Christopher J. Tame

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引用次数: 3

Abstract

The absolute configuration of two novel α_vβ₆ 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.

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测定治疗特发性肺纤维化的两种αvβ6整合素抑制剂的绝对构型，并研究芳香硼酸在含有c4 -氧取代基的克罗酮酸酯上的不对称1,4加成

通过降解相应的c3 -芳基取代丁内酯，建立了两种新型αvβ6整合素抑制剂的绝对构型。在(R)-BINAP存在的情况下，以四氟硼酸双(降冰片二烯)铑(I)为催化剂，在丁烯内酯上加成1,4芳基硼酸，建立了内酯的不对称合成构型，并通过x射线晶体学证实了该构型。本文还报道了含γ-氧取代基的芳香硼酸缀合到无环克罗酮酯上的研究。研究了三种Rh催化剂，其中对映选择性最高的是四氟硼酸双(降冰片二烯)铑。

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来源期刊

Tetrahedron, asymmetry 化学-无机化学与核化学

CiteScore

4.70

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Cessation. Tetrahedron: Asymmetry presents experimental or theoretical research results of outstanding significance and timeliness on asymmetry in organic, inorganic, organometallic and physical chemistry, as well as its application to related disciplines, especially bio-organic chemistry. The journal publishes critical reviews, original research articles and preliminary communications dealing with all aspects of the chemical, physical and theoretical properties of non-racemic organic and inorganic materials and processes. Topics relevant to the journal include: the physico-chemical and biological properties of enantiomers; strategies and methodologies of asymmetric synthesis; resolution; chirality recognition and enhancement; analytical techniques for assessing enantiomeric purity and the unambiguous determination of absolute configuration; and molecular graphics and modelling methods for interpreting and predicting asymmetric phenomena. Papers describing the synthesis or properties of non-racemic molecules will be required to include a separate statement in the form of a Stereochemistry Abstract, for publication in the same issue, of the criteria used for the assignment of configuration and enantiomeric purity.