Stereodivergent synthesis of cytotoxic pseudodistomin-like analogues from d-erythrofuranose

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron Pub Date : 2025-05-10 DOI:10.1016/j.tet.2025.134710

Martin Fábian , Andrej Kráľovský , Miroslava Martinková , Martina Bago Pilátová , Juraj Kuchár , Miroslava Litecká , Dávid Jáger

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Abstract

A simple stereodivergent route from d-erythrofuranose to pseudodistomin-based analogues was accomplished. The developed approach took advantage of both stereocentres of the starting material; an additional stereogenic centre was installed using an Overman rearrangement, and the extra carbon atoms present in the final C-alkyl piperidine-diols were successively installed via two Wittig olefinations and an olefin cross-metathesis reaction. The required 6-membered ring was formed by means of an alkylative cyclisation after activation of the primary alcohol functionality. The target molecules were screened in vitro for antiproliferative activity on a series of human malignant cell lines by MTT assay. Both prepared analogues exhibited similar behaviour in their capacity to alter the viability of the tested cells.

The synthetic strategy to these modified pseudodistomins has the potential to be extended to their enantiomeric congeners by simply substituting the starting material with l-erythrofuranose as the suitable chiron.

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从d-红呋喃糖立体发散合成细胞毒性假二stomin样类似物

一个简单的立体发散路线从d-红呋喃糖到基于假二甘醇的类似物完成。所开发的方法利用了起始材料的两个立体中心；用Overman重排法安装了一个额外的立体中心，最后的c -烷基哌啶二醇中的额外碳原子通过两次Wittig烯烃化和一次烯烃交叉复分解反应依次安装。所需的6元环是在伯醇官能团活化后通过烷基化环化形成的。用MTT法在体外筛选靶分子对一系列人恶性细胞系的抗增殖活性。两种制备的类似物在改变被试细胞的生存能力方面表现出相似的行为。通过简单地用l-红呋喃糖作为合适的chiron取代起始原料，这些修饰的假二stomins的合成策略有可能扩展到它们的对映异构体同源物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tetrahedron 化学-有机化学

CiteScore

3.90

自引率

4.80%

发文量

439

审稿时长

34 days

期刊介绍： Tetrahedron publishes full accounts of research having outstanding significance in the broad field of organic chemistry and its related disciplines, such as organic materials and bio-organic chemistry. Regular papers in Tetrahedron are expected to represent detailed accounts of an original study having substantially greater scope and details than that found in a communication, as published in Tetrahedron Letters. Tetrahedron also publishes thematic collections of papers as special issues and ''Reports'', commissioned in-depth reviews providing a comprehensive overview of a research area.