新型5-脱氧腺嘌呤类似物的灵活合成及生物学评价

Flexible synthesis and biological evaluation of novel 5-deoxyadenophorine analogues.

作者信息

Pearson Morwenna S M, Saad Rim Ouled, Dintinger Thierry, Amri Hassen, Mathé-Allainmat Monique, Lebreton Jacques

机构信息

Université de Nantes, CNRS, Laboratoire de Synthèse Organique, UMR 6513, Faculté des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.

出版信息

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3262-7. doi: 10.1016/j.bmcl.2006.03.035. Epub 2006 Apr 5.

DOI:10.1016/j.bmcl.2006.03.035

Abstract

Adenophorine and its 5-deoxy analogue have been identified as natural iminosugars with efficient glycosidase inhibitory effects. The syntheses and biological evaluation of two new series of 5-deoxyadenophorine analogues in their racemic form are reported. The compounds 12e and 13d bearing a C11 and C7 alkyl chain, respectively, were found to be potent inhibitors of the beta-glucosidase from almond with Ki near to 60 microM. The compounds 13a,d which possess a 3,4-cis stereochemistry were efficient on glucosidases but also on the beta-galactosidase, what was not observed with the 3,4-trans series 12.

摘要

腺嘌呤核苷及其5-脱氧类似物已被鉴定为具有高效糖苷酶抑制作用的天然亚氨基糖。本文报道了两个新系列外消旋形式的5-脱氧腺嘌呤核苷类似物的合成及生物学评价。分别带有C11和C7烷基链的化合物12e和13d被发现是杏仁β-葡萄糖苷酶的有效抑制剂，其抑制常数（Ki）接近60微摩尔。具有3,4-顺式立体化学结构的化合物13a、d对葡萄糖苷酶有效，对β-半乳糖苷酶也有效，而具有3,4-反式结构的系列12化合物则未观察到这种情况。

相似文献

1

Flexible synthesis and biological evaluation of novel 5-deoxyadenophorine analogues.

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3262-7. doi: 10.1016/j.bmcl.2006.03.035. Epub 2006 Apr 5.

2

N- and C-alkylation of seven-membered iminosugars generates potent glucocerebrosidase inhibitors and F508del-CFTR correctors.

Org Biomol Chem. 2014 Nov 28;12(44):8977-96. doi: 10.1039/c4ob00325j.

3

First total synthesis of 1-O-beta-D-glucopyranosyl-5-deoxyadenophorine and its aglycon congener: determination of the absolute configuration.

J Org Chem. 2004 Mar 5;69(5):1497-503. doi: 10.1021/jo035522m.

4

1-Aza-sugars from D-glucose. Preparation of 1-deoxy-5-dehydroxymethyl-nojirimycin, its analogues and evaluation of glycosidase inhibitory activity.

Bioorg Med Chem. 2002 Jul;10(7):2155-60. doi: 10.1016/s0968-0896(02)00073-1.

5

Homonojirimycin isomers and N-alkylated homonojirimycins: structural and conformational basis of inhibition of glycosidases.

J Med Chem. 1998 Jul 2;41(14):2565-71. doi: 10.1021/jm970836l.

6

Synthesis and biological evaluation of glycosidase inhibitors: gem-difluoromethylenated nojirimycin analogues.

J Med Chem. 2006 May 18;49(10):2989-97. doi: 10.1021/jm060066q.

7

Synthesis of S-alkylated sulfonium-ions and their glucosidase inhibitory activities against recombinant human maltase glucoamylase.

Carbohydr Res. 2007 May 21;342(7):901-12. doi: 10.1016/j.carres.2007.01.018. Epub 2007 Feb 7.

8

C-Alkyl 5-membered ring imino sugars as new potent cytotoxic glucosylceramide synthase inhibitors.

Org Biomol Chem. 2006 Dec 21;4(24):4437-9. doi: 10.1039/b613460b. Epub 2006 Nov 2.

9

Convergent approach toward the synthesis of the stereoisomers of C-6 homologues of 1-deoxynojirimycin and their analogues: evaluation as specific glycosidase inhibitors.

J Org Chem. 2006 Oct 27;71(22):8481-8. doi: 10.1021/jo061455v.

10

Skeletal rearrangement of seven-membered iminosugars: synthesis of (-)-adenophorine, (-)-1-epi-adenophorine and derivatives and evaluation as glycosidase inhibitors.

Bioorg Med Chem. 2013 Aug 15;21(16):4803-12. doi: 10.1016/j.bmc.2013.03.035. Epub 2013 Apr 2.

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍。

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

文档翻译

学术文献翻译模型，支持多种主流文档格式。