Adaptable synthesis of chondroitin sulfate disaccharide subtypes preprogrammed for regiospecific O-sulfation

Wootton, Hannah S., Berry, Sian S., Ferguson, Elaine L. ORCID: https://orcid.org/0000-0002-0125-0234, Mahon, Clare S. and Miller, Gavin J. 2024. Adaptable synthesis of chondroitin sulfate disaccharide subtypes preprogrammed for regiospecific O-sulfation. European Journal of Organic Chemistry 27 (40) , e202400587. 10.1002/ejoc.202400587

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Abstract

A divergent synthetic route to chondroitin sulfate (CS) disaccharide precursors, including rarer subtypes such as CS-D, has been developed. From common intermediates, a series of thioglycoside D-glucosyl donors and 4,6-O-benzylidene protected D-galactosamine acceptors are utilised in a robust glycosylation reaction, achieving β-selectivity and consistent yields (60-75%) on scales >2.0 g. A post-glycosylation oxidation to D-glucuronic acid and orthogonal protecting groups delivers access to CS-A, CS-C, CS-D, CS-E and CS-O precursor subtypes. Of further note is a 4-O-benzyl regioselective reductive ring opening of a 4,6-O-benzylidene protected disaccharide using dichlorophenylborane (PhBCl­2) and triethylsilane (Et3SiH) to access a CS-D precursor, in 73% yield over two steps. Finally, synthesis of a 6-O-sulfated CS-C disaccharide containing a conjugable anomeric allyl tether is completed. These materials will provide a benchmark to further synthesise and study chondroitin sulfates.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Subjects:	Q Science > QD Chemistry
Publisher:	Wiley
ISSN:	1434-193X
Funders:	EPSRC
Date of First Compliant Deposit:	22 August 2024
Date of Acceptance:	27 July 2024
Last Modified:	05 Nov 2024 13:23
URI:	https://orca.cardiff.ac.uk/id/eprint/171525

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