Exploring the Chemical Reactivity of Triisopropylsilyl Dialkynylmethanol for the Synthesis of Dialkynylcarbinol‐Related Compounds

IF 2.7 3区化学 Q2 CHEMISTRY, ORGANIC

European Journal of Organic Chemistry Pub Date : 2025-09-23 DOI:10.1002/ejoc.202500762

Maria Vieira de Brito, François‐Xavier Toublet, Margaux Bossuat, Dalila Maria Barbosa Davi, Diana Kelly Almeida, Thiago de Sousa Fonseca, Fátima Miranda Nunes, Marcos Carlos de Mattos, Maëlle Caroff, Sébastien Britton, Stéphanie Ballereau, Valérie Maraval, Maria Conceição Ferreira Oliveira, Yves Génisson, Vania Bernardes‐Génisson

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引用次数: 0

Abstract

Prompted by the pharmacological relevance of lipidic alkynylcarbinols, 1‐(triisopropylsilyl)penta‐1,4‐diyn‐3‐ol is exploited as a versatile C5 organic framework. Selective functionalization of this dissymmetrical dialkynylcarbinol precursor is achieved via the creation of either a Csp–Csp (alkyne), a Csp–Csp2 (alkene and aryl), or a Csp–Csp3 (RCHOH) bond. A novel series of racemic HSD17B11‐bioactivated procytotoxic acetylenic lipids is accessed that revealed, amongst the most potent to date, with IC50 down to 27 nM on osteosarcoma U2OS cells. Click‐type 1,3‐dipolar cycloadditions, such as a copper‐catalyzed reaction with a long‐chain alkyl azide (CuAAC) and a base‐promoted reaction with a lipidic nitrile oxide, are first described in a racemic version. Preparation of both enantiomers of 1‐(triisopropylsilyl)penta‐1,4‐diyn‐3‐ol through kinetic enzymatic resolution with CAL‐B immobilized on acrylic resin is carefully optimized. Finally, the use of resolved samples in 1,3‐dipolar cycloaddition reactions leads to the enantioenriched cycloadducts without significant epimerization of the carbinol center.

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探索三异丙基硅基二炔基甲醇合成二炔基甲醇相关化合物的化学反应性

由于脂质炔基醇的药理学相关性，1‐（三异丙基硅基）戊- 1,4‐二炔- 3‐醇被开发为一种多功能的C5有机框架。这种不对称二炔基甲醇前体通过Csp-Csp（炔）、Csp-Csp2（烯和芳基）或Csp-Csp3 （RCHOH）键的形成实现了选择性功能化。研究人员获得了一系列新的外消旋HSD17B11生物活性原细胞毒性乙酰脂类，这些脂类是迄今为止最有效的，其对骨肉瘤U2OS细胞的IC50低至27 nM。点击型1,3偶极环加成，如铜催化的与长链烷基叠氮化物（CuAAC）的反应和碱促进的与脂质氧化腈的反应，首先以外消旋形式描述。以丙烯酸树脂为固定载体的CAL - B，通过动态酶解法制备1 -（三异丙基硅基）五- 1,4 -二炔- 3 -醇两种对映体。最后，在1,3‐偶极环加成反应中使用溶解样品可以得到对映体富集的环加合物，而不会对甲醇中心产生明显的外映作用。

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来源期刊

European Journal of Organic Chemistry 化学-有机化学

CiteScore

5.40

自引率

3.60%

发文量

752

审稿时长

1 months

期刊介绍： The European Journal of Organic Chemistry (2019 ISI Impact Factor 2.889) publishes Full Papers, Communications, and Minireviews from the entire spectrum of synthetic organic, bioorganic and physical-organic chemistry. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. The following journals have been merged to form two leading journals, the European Journal of Organic Chemistry and the European Journal of Inorganic Chemistry: Liebigs Annalen Bulletin des Sociétés Chimiques Belges Bulletin de la Société Chimique de France Gazzetta Chimica Italiana Recueil des Travaux Chimiques des Pays-Bas Anales de Química Chimika Chronika Revista Portuguesa de Química ACH—Models in Chemistry Polish Journal of Chemistry.