d-Glucuronate and d-Glucuronate Glycal Acceptors for the Scalable Synthesis of d-GlcN-α-1,4-d-GlcA Disaccharides and Modular Assembly of Heparan Sulfate

Reported herein is a scalable chemical synthesis of disaccharidebuilding blocks for heparan sulfate (HS) oligosaccharide assembly.The use of d-glucuronate-based acceptors for dehydrativeglycosylation with d-glucosamine partners is explored, enablingdiastereoselective synthesis of appropriately prote...

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Bibliographic Details
Published in:Journal of organic chemistry Vol. 88; no. 15; pp. 11130 - 11139
Main Authors: Pongener, Imlirenla, Miller, Gavin J. J.
Format: Journal Article
Language:English
Published: WASHINGTON Amer Chemical Soc 04.08.2023
Subjects:
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
HERPES-SIMPLEX-VIRUS
ACTIVATION
ACID
OLIGOSACCHARIDES
MOIETY
STRATEGY
DODECASACCHARIDES
GLYCOSYL PHOSPHATES
CHEMICAL-SYNTHESIS
BINDING
ISSN:0022-3263, 1520-6904, 1520-6904
Online Access:Get more information
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Summary:Reported herein is a scalable chemical synthesis of disaccharidebuilding blocks for heparan sulfate (HS) oligosaccharide assembly.The use of d-glucuronate-based acceptors for dehydrativeglycosylation with d-glucosamine partners is explored, enablingdiastereoselective synthesis of appropriately protected HS disaccharidebuilding blocks (d-GlcN-& alpha;-1,4-d-GlcA) on amultigram scale. Isolation and characterization of key donor (1,2glycal)- and acceptor (ortho-ester, anhydro)-derived side productsensure methodology improvements to reduce their formation; protectingthe d-glucuronate acceptor at the anomeric position witha para-methoxyphenyl unit proves optimal. We alsointroduce glycal uronate acceptors, showing them to be comparativein reactivity to their pyranuronate counterparts. Taken together,this gram-scale access offers the capability to explore the iterativeassembly of defined HS sequences containing the d-GlcN-& alpha;-1,4-d-GlcA repeat, highlighted by completing this for two tetrasaccharidesyntheses.
Bibliography:UKRI
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ISSN:0022-3263
1520-6904
1520-6904
DOI:10.1021/acs.joc.3c01108