Total Synthesis of Taxol Enabled by Inter- and Intramolecular Radical Coupling Reactions.

Autor: Imamura Y; Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan., Takaoka K; Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan., Komori Y; Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan., Nagatomo M; Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan., Inoue M; Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 Mar 01; Vol. 62 (10), pp. e202219114. Date of Electronic Publication: 2023 Feb 01.
DOI: 10.1002/anie.202219114
Abstrakt: Taxol is a clinically used drug for the treatment of various types of cancers. Its 6/8/6/4-membered ring (ABCD-ring) system is substituted by eight oxygen functional groups and flanked by four acyl groups, including a β-amino acid side chain. Here we report a 34-step total synthesis of this unusually oxygenated and intricately fused structure. Inter- and intramolecular radical coupling reactions connected the A- and C-ring fragments and cyclized the B-ring, respectively. Functional groups of the A- and C-rings were then efficiently decorated by employing newly developed chemo-, regio-, and stereoselective reactions. Finally, construction of the D-ring and conjugation with the β-amino acid delivered taxol. The powerful coupling reactions and functional group manipulations implemented in the present synthesis provide new valuable information for designing multistep target-oriented syntheses of diverse bioactive natural products.
(© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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