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–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.