Total Synthesis of Thiamyxins A-C and Thiamyxin E, a Potent Class of RNA-Virus-Inhibiting (Cyclo)depsipeptides.

Autor: Bauer K; Organic Chemistry I, Saarland University, Campus C4.2, 66123, Saarbrücken, Germany., Kazmaier U; Organic Chemistry I, Saarland University, Campus C4.2, 66123, Saarbrücken, Germany.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 Aug 07; Vol. 62 (32), pp. e202305445. Date of Electronic Publication: 2023 Jul 03.
DOI: 10.1002/anie.202305445
Abstrakt: We present the first total synthesis of the thiamyxins A-C and the now fully characterized thiamyxin E, an interesting class of thiazole- and thiazoline-rich depsipeptides with diverse antiviral activity. The synthesis features a parallel closing of two methyl thiazoline units, with low epimerization of the very labile adjacent stereocenter. It also includes the three-step synthesis of an uncommon hydroxy acid and the oxidation-free elimination of a phenylselenide to form a dehydroalanine moiety. The exploitation of the acid-labile stereocenter at the isoleucine moiety and the reopening of the macrolactones gave access to the four thiamyxins with good yields and diastereomeric purities from a single precursor. The modular total synthesis allows further testing of the biological activity and gives opportunities to explore the pharmacophore and antiviral target through derivatization.
(© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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