α-Selective Solid-Phase Synthesis of Glycosyl Phosphate Repeating Structure Via the Phosphoramidite Method.

Autor: Kawato K; Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda Chiba, 278-8510, Japan., Sato K; Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda Chiba, 278-8510, Japan., Wada T; Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda Chiba, 278-8510, Japan.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Oct 11; Vol. 30 (57), pp. e202401226. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.1002/chem.202401226
Abstrakt: Lipophosphoglycans (LPGs) are found on the surface of Leishmania, a protozoan parasite, and are immunologically important. Herein, disaccharide 1-phosphate repeating units of LPGs were successfully synthesized on a solid support with high anomeric purity using a disaccharide α-1-phosphoramidite building block. To enhance solubility in the reaction solvent, hydroxy-protecting groups in the form of para-t-butylbenzoyl were introduced to the building block. The saccharide chain was elongated via stable glycosyl boranophosphate linkages, followed by the conversion of inter-sugar linkages to phosphodiester counterparts using an oxaziridine derivative. The addition of a silylating reagent post-reaction with the oxaziridine derivative efficiently facilitated the conversion of boranophosohodiesters to phosphodiesters. This method enabled the α-selective synthesis of up to 15 repeating units, marking the longest homogeneous repeating units of LPGs synthesized chemically. Given the chain length equivalence to native LPGs, the method developed herein holds promise for advancing anti-Leishmanial pharmaceuticals and vaccines.
(© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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