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Article Dans Une Revue Synthesis: Journal of Synthetic Organic Chemistry Année : 2018

From natural to artificial antitumor lipidic alkynylcarbinols: Asymmetric synthesis, enzymatic resolution, and refined SARs

Résumé

Among acetylenic natural products, chiral lipidic alkynylcarbinol (LAC) metabolites, mostly extracted from marine sponges, have revealed a broad spectrum of biological activities, in particular, remarkable antitumor cytotoxicity. With reference to one of the simplest natural representatives, [(S)-eicos-(4E)-en-1-yn-3-ol], and a given cancer cell line (HCT116), combined extensive efforts in chemical synthesis (relying on the use of a large chemical toolbox) and biological analysis (in vitro tests), have provided systematic structure–activity relationships (SARs) where the initially selected four structural parameters appear as independent principal components: (i) and (ii) the sp/sp2 content and extent of the terminal and internal unsaturations adjacent to the carbinol center, (iii) the absolute configuration of the latter, (iv) the length of the n-aliphatic backbone. Two key criteria have also been established regarding the functional alkynylcarbinol pharmacophore: the alkynylcarbinol unit must be both secondary and terminal (i.e., substituted by a short ethynyl or ethenyl C2 group). This review is intended to provide a further illustration of the value of a simple rational approach for drug design, and to act as a benchmark for future optimization of LACs as antitumor agents.
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Dates et versions

hal-01952874 , version 1 (12-12-2018)

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Dymytrii Listunov, Etienne Joly, Pauline Rullière, Hafida Gaspard, Vania Bernardes-Génisson, et al.. From natural to artificial antitumor lipidic alkynylcarbinols: Asymmetric synthesis, enzymatic resolution, and refined SARs. Synthesis: Journal of Synthetic Organic Chemistry, 2018, 50 (16), pp.3114-3130. ⟨10.1055/s-0037-1610006⟩. ⟨hal-01952874⟩
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