Exploring the chemical reactivity of triisopropylsilyl dialkynyl methanol for the synthesis of dialkynylcarbinol-related compounds
Résumé
Prompted by the pharmacological relevance of lipidic alkynylcarbinols, 1-(triisopropyl)silyl)penta-1,4-diyn-3-ol was exploited as a versatile C5 organic framework. Selective functionalization of this dissymmetrical dialkynylcarbinol precursor was achieved via the creation of either a Csp-Csp (alkyne), a Csp-Csp2 (alkene and aryl) or a Csp-Csp3 (RCHOH) bond. This allowed to access a novel racemic series of bioinspired acetylenic lipids 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 were then first described in a racemic version. Preparation of both enantiomers of 1-(triisopropyl)silyl)penta-1,4-diyn-3-ol by kinetic enzymatic resolution with CAL-B immobilized on acrylic resin was carefully optimized. Finally, the use of resolved samples in 1,3-dipolar cycloaddition reactions led to the enantioenriched cycloadducts without significant epimerization of the carbinol center.
Domaines
Chimie
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