Total Synthesis of a Noricumazole A Library and Evaluation of HCV Inhibition

被引：17

作者：

Barbier, Jenny ^{[1
,2
]}

Wegner, Jens ^{[1
,2
]}

Benson, Stefan ^{[1
,2
]}

Gentzsch, Juliane ^{[3
]}

Pietschmann, Thomas ^{[3
]}

Kirschning, Andreas ^{[1
,2
]}

机构：

[1] Leibniz Univ Hannover, Inst Organ Chem, D-30167 Hannover, Germany

[2] Leibniz Univ Hannover, Zentrum Biomol Wirkstoffe BMWZ, D-30167 Hannover, Germany

[3] Zentrum Expt & Klin Infekt Forsch GmbH, TWINCORE, D-30625 Hannover, Germany

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2012年 / 18卷 / 29期

关键词：

compound library; Hepatitis C virus; iron catalysis; natural products; total synthesis; HIGHLY ENANTIOSELECTIVE REDUCTION; ASYMMETRIC ALKYNYLATION; KETONES; ALDEHYDES; ALKYNES; MILD; PRECATALYST; COMPLEXES; BROMIDES; CHLORIDE;

D O I：

10.1002/chem.201104042

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The total synthesis of 16 new ion channel inhibitors derived from noricumazole A, a secondary metabolite from the myxobacterium Sorangium cellulosum, is reported. Particular focus of library design is put on stereochemical permutations in the central region (C9 and C11), the oxazole moiety and the side chain at C4 of the isochromanone moiety. Noricumazole A and all new noricumazole derivatives were tested in an assay system with inhibitory effect on the hepatitis C virus (HCV) life cycle. Most of them are moderate to strong HCV inhibitors (350 nM6 nM) but also exert pronounced cytotoxicity. In contrast, the thiazole analogue of noricumazole A is a strong HCV inhibitor with only moderate cytotoxic property. It may become a lead structure with a good therapeutic index (CC50/IC50) of greater than 10.

引用

页码：9083 / 9090

页数：8

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