Total Synthesis of Tiacumicin B: Study of the Challenging β-Selective Glycosylations*.

Autor: Tresse C; Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Université Paris-Saclay, 91198, Gif-sur-Yvette, France., François-Heude M; Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Université Paris-Saclay, 91198, Gif-sur-Yvette, France., Servajean V; Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Université Paris-Saclay, 91198, Gif-sur-Yvette, France., Ravinder R; Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Université Paris-Saclay, 91198, Gif-sur-Yvette, France., Lesieur C; Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Université Paris-Saclay, 91198, Gif-sur-Yvette, France., Geiben L; Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Université Paris-Saclay, 91198, Gif-sur-Yvette, France., Jeanne-Julien L; C-Tac, CitCom, UMR 8038, Faculté de Pharmacie, CNRS-Université de Paris, avenue de l'Observatoire 4, 75006, Paris, France., Steinmetz V; Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Université Paris-Saclay, 91198, Gif-sur-Yvette, France., Retailleau P; Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Université Paris-Saclay, 91198, Gif-sur-Yvette, France., Roulland E; C-Tac, CitCom, UMR 8038, Faculté de Pharmacie, CNRS-Université de Paris, avenue de l'Observatoire 4, 75006, Paris, France., Beau JM; Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Université Paris-Saclay, 91198, Gif-sur-Yvette, France.; Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), UMR 8182, Univ. Paris-Sud and CNRS, Université Paris-Saclay, 91405, Orsay, France., Norsikian S; Institut de Chimie des Substances Naturelles, UPR 2301, CNRS Université Paris-Saclay, 91198, Gif-sur-Yvette, France.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2021 Mar 17; Vol. 27 (16), pp. 5230-5239. Date of Electronic Publication: 2021 Feb 18.
DOI: 10.1002/chem.202005102
Abstrakt: We give a full account of the total synthesis of tiacumicin B (Tcn-B), a natural glycosylated macrolide with remarkable antibiotic properties. Our strategy is based on our experience with the synthesis of the tiacumicin B aglycone and on unique 1,2-cis-glycosylation steps. We used sulfoxide anomeric leaving-groups in combination with a remote 3-O-picoloyl group on the donors that allowed highly β-selective rhamnosylation and noviosylation that rely on H-bond-mediated aglycone delivery. The rhamnosylated C1-C3 fragment was anchored to the C4-C19 aglycone fragment by a Suzuki-Miyaura cross-coupling. Ring-size-selective Shiina macrolactonization provided a semiglycosylated aglycone that was engaged directly in the noviolysation step with a virtually total β-selectivity. Finally, a novel deprotection method was devised for the removal of a 2-naphthylmethyl ether on a phenol, and efficient removal of all the protecting groups provided synthetic tiacumicin B.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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