Harnessing Free Sulfate Groups in Glycosylation Reactions

Maki, Yuta; Manbo, Akihiro; Abe, Junpei; Nobutou, Hiroki; Hirao, Kohtaro; Okamoto, Ryo; Izumi, Masayuki; Yamanaka, Shusuke; Okumura, Mitsutaka; Kajihara, Yasuhiro

doi:https://doi.org/10.1002/anie.202416743

Harnessing Free Sulfate Groups in Glycosylation Reactions

Maki, Yuta; Manbo, Akihiro; Abe, Junpei et al.

Angewandte Chemie - International Edition, 2025, 64(4), e202416743

Number of Access:896（2025-09-08 07:50 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/100187

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Title	Harnessing Free Sulfate Groups in Glycosylation Reactions
Creator	NRID 1000000805559 1000000805559 researchmap permalink ymou ymou Scopus Author ID 57188724477 57188724477 CreatorName Maki, Yuta
	CreatorName Manbo, Akihiro
	NRID 1000000798522 1000000798522 ORCID 0000-0003-2108-2570 0000-0003-2108-2570 researchmap permalink junpeiabe junpeiabe CreatorName Abe, Junpei
	CreatorName Nobutou, Hiroki
	ORCID 0000-0001-7721-4718 0000-0001-7721-4718 researchmap permalink pkpkkh pkpkkh CreatorName Hirao, Kohtaro
	NRID 1000030596870 1000030596870 ORCID 0000-0001-9529-2525 0000-0001-9529-2525 researchmap permalink ryookamoto ryookamoto Scopus Author ID 36194293500 36194293500 CreatorName Okamoto, Ryo
	CreatorName Izumi, Masayuki
	NRID 1000010324865 1000010324865 researchmap permalink read0068708 read0068708 CreatorName Yamanaka, Shusuke
	NRID 1000040356712 1000040356712 researchmap permalink read0118533 read0118533 Scopus Author ID 7203040649 7203040649 CreatorName Okumura, Mitsutaka
	NRID 1000050275020 1000050275020 ORCID 0000-0002-6656-2394 0000-0002-6656-2394 researchmap permalink read0048540 read0048540 Scopus Author ID 7006984179 7006984179 CreatorName Kajihara, Yasuhiro
Subject	chondroitin sulfate
	free sulfate group
	glycosaminoglycan
	glycosylation
Description	Maki Y., Manbo A., Abe J., et al. Harnessing Free Sulfate Groups in Glycosylation Reactions. Angewandte Chemie - International Edition 64, e202416743 (2025); https://doi.org/10.1002/anie.202416743.
Abstract	General strategies for synthesizing sulfated oligosaccharides employ the protection of sulfate groups for glycosylation or post-sulfation after the synthesis of oligosaccharides. However, the chemical behavior of free sulfate groups in glycosylation reactions has not been thoroughly studied. We examined several glycosyl donors with free sulfate groups, but neither glycosyl imidates nor thioglycosides achieved products. Conversely, activating 6-sulfated GalNAc donors with either a 2-NTroc group or 2-O-acetyl group using an ortho-hexynylbenzoate group at the anomeric position yielded β-glycosides in good yield. These results indicate that glycosylations with a free sulfate group can be performed and that the neighboring group participation of 2-NHTroc and 2-O-acetyl groups works even with an unprotected sulfate group at the 6-position. Ab initio calculations supported the formation of acyloxonium-cation via 2-O-acyl participation. Additionally, glycosylation reactions under various counter cations of the sulfate group, such as Na+, Li+, K+, Ba2+, and pyridinium were examined. Results showed that sodium and lithium salt donors yielded the products in good yield. These results were also supported by ab initio calculations. Practical glycosylation reactions between disaccharide donor-acceptor pairs with free sulfate groups successfully yielded the sulfated tetrasaccharides. This study also discusses how a sodium salt acts as a protecting group during glycosylation.
Publisher	John Wiley and Sons Inc
Source Title	Angewandte Chemie - International Edition
Volume (Issue)	64(4)
Page	e202416743
Date of Issued	2025-01-21
Language	English
Handle URL	https://hdl.handle.net/11094/100187
PISSN	14337851
eISSN	15213773
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1002/anie.202416743
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Angewandte Chemie - International Edition. 2025, 64(4), p. e202416743
DC.title	Harnessing Free Sulfate Groups in Glycosylation Reactions
DC.creator	Maki, Yuta
	Manbo, Akihiro
	Abe, Junpei
	Nobutou, Hiroki
	Hirao, Kohtaro
	Okamoto, Ryo
	Izumi, Masayuki
	Yamanaka, Shusuke
	Okumura, Mitsutaka
	Kajihara, Yasuhiro
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-01-21
DC.identifier	https://doi.org/10.1002/anie.202416743
DC.subject	chondroitin sulfate
	free sulfate group
	glycosaminoglycan
	glycosylation
DC.description	Maki Y., Manbo A., Abe J., et al. Harnessing Free Sulfate Groups in Glycosylation Reactions. Angewandte Chemie - International Edition 64, e202416743 (2025); https://doi.org/10.1002/anie.202416743.
DCTERMS.abstract	General strategies for synthesizing sulfated oligosaccharides employ the protection of sulfate groups for glycosylation or post-sulfation after the synthesis of oligosaccharides. However, the chemical behavior of free sulfate groups in glycosylation reactions has not been thoroughly studied. We examined several glycosyl donors with free sulfate groups, but neither glycosyl imidates nor thioglycosides achieved products. Conversely, activating 6-sulfated GalNAc donors with either a 2-NTroc group or 2-O-acetyl group using an ortho-hexynylbenzoate group at the anomeric position yielded β-glycosides in good yield. These results indicate that glycosylations with a free sulfate group can be performed and that the neighboring group participation of 2-NHTroc and 2-O-acetyl groups works even with an unprotected sulfate group at the 6-position. Ab initio calculations supported the formation of acyloxonium-cation via 2-O-acyl participation. Additionally, glycosylation reactions under various counter cations of the sulfate group, such as Na+, Li+, K+, Ba2+, and pyridinium were examined. Results showed that sodium and lithium salt donors yielded the products in good yield. These results were also supported by ab initio calculations. Practical glycosylation reactions between disaccharide donor-acceptor pairs with free sulfate groups successfully yielded the sulfated tetrasaccharides. This study also discusses how a sodium salt acts as a protecting group during glycosylation.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	100187
citation_title	Harnessing Free Sulfate Groups in Glycosylation Reactions
citation_author	Maki, Yuta
	Manbo, Akihiro
	Abe, Junpei
	Nobutou, Hiroki
	Hirao, Kohtaro
	Okamoto, Ryo
	Izumi, Masayuki
	Yamanaka, Shusuke
	Okumura, Mitsutaka
	Kajihara, Yasuhiro
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2025-01-21
citation_journal_title	Angewandte Chemie - International Edition
citation_volume	64
citation_issue	4
citation_firstpage	e202416743
citation_doi	https://doi.org/10.1002/anie.202416743
citation_public_url	https://hdl.handle.net/11094/100187

Harnessing Free Sulfate Groups in Glycosylation Reactions

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