6‐Azido‐6‐deoxy‐l‐idose as a Hetero‐Bifunctional Spacer for the Synthesis of Azido‐Containing Chemical Probes. Issue 36 (2nd August 2016)

• Record Type: Journal Article
• Authors: Hamagami, Hiroki; Kumazoe, Motofumi; Yamaguchi, Yoshiki; Fuse, Shinichiro; Tachibana, Hirofumi; Tanaka, Hiroshi
• Is Part Of: Chemistry. Volume 22:Issue 36(2016)
• Page Start: 12884
• Page End: 12890
• Publication Date: 2016-08-02
• Subjects: aldehydes -- C-glycosylation -- Lewis acids -- oximes -- phytochemistry; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201602044
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The design of 6‐azido‐6‐deoxy‐l ‐idose for use as a hetero‐bifunctional spacer is reported. The hemiacetal at one terminus is an equivalent of an aldehyde and can react with nucleophiles, such as amino groups and electron‐rich aromatics. The azido group at the other terminus bio‐orthogonally undergoes a Hüisgen [3+2] cycloaddition with an acetylene. The idose derivative exhibited a higher level of reactivity towards oxime formation than a corresponding glucose derivative. The 13 C NMR spectrum of the uniformly 13 C‐labeled 6‐azido‐idose indicated that the acyclic forms of the sugar totaled 0.3 % of all the isomers, whereas those of glucose totaled 0.01 %. The larger population of the acyclic forms of the idose derivative would result in higher reactivity towards electrophilic addition in comparison with glucose derivatives. Finally, we prepared a C ‐idosyl epigallocatechin gallate (EGCG) that bears an azido group through C ‐glycosylation of EGCG with 6‐azido‐idose. This glycosyl form of the C ‐idosyl EGCG exhibited a cytotoxicity against U266 cells that was comparable to that of EGCG. These results suggested that the EGCG derivative could be used as an effective chemical probe for the elucidation of EGCG biological functions. Abstract : Bifunctional : 6‐Azido‐6‐deoxy‐l ‐idose was used as a hetero‐bifunctional spacer. Its hemiacetal function exhibited higher reactivity with nucleophiles in comparison with glucose derivatives because the acyclic forms of the idose derivative were more than ten times those of glucose (see scheme). The hetero‐biofunctional spacer allowed the preparation of an azido‐containing epigallocatechin gallate (EGCG) by direct C ‐glycosylation of EGCG in water.