Synthesis of carba-cyclophellitols: a new class of carbohydrate mimetics,European Journal of Organic Chemistry

当前位置： X-MOL 学术 › Eur. J. Org. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Synthesis of carba-cyclophellitols: a new class of carbohydrate mimetics
European Journal of Organic Chemistry ( IF 2.5 ) Pub Date : 2018-02-14 , DOI: 10.1002/ejoc.201701601
Thomas J. M. Beenakker ₁ , Dennis P. A. Wander ₁ , Jeroen D. C. Codée ₁ , Johannes M. F. G. Aerts ₂ , Gijsbert A. van der Marel ₁ , Herman S. Overkleeft ₁

Affiliation

Cyclophellitol and cyclophellitol aziridine are potent and irreversible inhibitors of retaining β-glucosidases. They preferentially adopt a 4H3 half-chair conformation, thereby mimicking the substrate-transition-state conformation characteristic of retaining β-glucosidases. As a consequence, both compounds bind tightly to the enzyme active site, and attack of the catalytic nucleophile onto the epoxide/aziridine results in enzyme deactivation. Replacement of the epoxide oxygen in cyclophellitol by a (substituted) carbon yielded carba-cyclophellitols, a conceptually new class of inhibitors of retaining β-glucosidases, as we demonstrated in a recent communication. In this paper, in-depth synthetic studies of this class of compounds are described, and the preparation of a comprehensive set of structurally and configurationally new carba-cyclophellitols is presented.

中文翻译：

carba-cyclophellitols 的合成：一类新的碳水化合物模拟物

Cyclophellitol 和 cyclophellitol aziridine 是保留 β-葡萄糖苷酶的有效且不可逆的抑制剂。它们优先采用 4H3 半椅构象，从而模仿保留 β-葡萄糖苷酶的底物-过渡态构象特征。因此，两种化合物都与酶活性位点紧密结合，催化亲核试剂对环氧化物/氮丙啶的攻击导致酶失活。正如我们在最近的通讯中所证明的那样，用（取代的）碳取代环酚醇中的环氧化物氧产生了卡巴环酚醇，这是一种概念上新的保留 β-葡糖苷酶的抑制剂。在本文中，描述了对此类化合物的深入合成研究，

更新日期：2018-02-14

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11