Exploring the Chemical Reactivity of Triisopropylsilyl Dialkynylmethanol for the Synthesis of Dialkynylcarbinol‐Related Compounds
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–Csp 2 (alkene and aryl), or a Csp–Csp 3 (RCHOH) bond. A novel series of racemic HSD17B11‐bioactivated procytotoxic acetylenic lipids is accessed that revealed, amongst the most potent to date, with IC 50 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.
Authors
- Vania Bernardes‐Génisson (ORCID: https://orcid.org/0000-0002-2937-6787)
- Maria da Conceição Ferreira de Oliveira (ORCID: https://orcid.org/0000-0002-7445-2347)
- Thiago de Sousa Fonseca (ORCID: https://orcid.org/0000-0001-7934-8728)
- François‐Xavier Toublet (ORCID: https://orcid.org/0000-0001-5630-6920)
- Margaux Bossuat
- Dalila Maria Barbosa Davi
- Maria Vieira de Brito (ORCID: https://orcid.org/0000-0001-6259-712X)
- Fátima Miranda Nunes (ORCID: https://orcid.org/0000-0002-7658-5901)
- Sébastien Britton (ORCID: https://orcid.org/0000-0002-7008-5316)
- Marcos Carlos de Mattos (ORCID: https://orcid.org/0000-0003-4291-5199)
- Stéphanie Ballereau (ORCID: https://orcid.org/0000-0002-7250-6188)
- Yves Génisson (ORCID: https://orcid.org/0000-0002-3647-4617)
- Maëlle Caroff (ORCID: https://orcid.org/0009-0008-3387-6013)
- Valérie Maraval
- Diana Kelly Castro de Almeida
Institutions
- Centre National de la Recherche Scientifique (FR)
- Universidade Federal do Ceará (BR)
- Instituto Federal de Educação, Ciência e Tecnologia do Ceará (BR)
- Institut de Pharmacologie et de Biologie Structurale (FR)
- Laboratoire de Chimie de Coordination (FR)
- Molécules d'Intérêt Biologique (FR)
Publication Details
- Journal
- European Journal of Organic Chemistry
- Published
- 2025-09-23
- DOI
- https://doi.org/10.1002/ejoc.202500762
- Citations
- 1
- Primary Topic
- Catalytic Alkyne Reactions
- Type
- article
- Field-Weighted Citation Impact
- 0.94