Premium
Synthesis and Biological Evaluation of O‐Methylated Glycolipids Related to PGLs via Direct Stereoselective Glycosidation and Sequential Suzuki–Miyaura Coupling using Boracyclane
Author(s) -
Sato Ko,
Omahdi Zakaria,
Shibata Kensuke,
Sonoda Kohhei,
Yamasaki Sho,
Tanaka Hiroshi
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201703684
Subject(s) - glycolipid , stereoselectivity , chemistry , glycoside , selectivity , aryl , sugar , stereochemistry , glycosyltransferase , combinatorial chemistry , organic chemistry , biochemistry , catalysis , enzyme , alkyl
Synthesis of O‐methylated glycolipids via direct stereoselective glycosidation whose sugar moieties are related to those in phenolic glycolipids (PGLs) is reported. Treatment of 2‐ O ‐methyl‐rhamnosyl imidates with I 2 and n Bu 4 NOTf resulted in their activation under low temperature and provided the α‐rhamnosides with excellent α‐selectivity. n Bu 4 NOTf enhanced the electorophilicity of iodine. This methodology improved the efficiency of the synthesis of both PGL‐1 and PGL‐tb1 sugars. The process involved the formation of 2‐ O ‐naphthylmethyl‐α‐rhamnoside and 2‐ O ‐methyl‐α‐fucoside. Sequential Suzuki–Miyaura coupling using synthetic glycosides, boracyclane, and aryl bromides provided glycolipids related to PGL sugars, and was accomplished with a one‐pot process. Finally, we elucidated the immunosuppressive activities of all these synthetic compounds and found that a phenyl 3‐ O ‐α‐rhamnosyl‐2‐ O ‐methyl‐α‐rhamnoside possessing a 6‐(2‐naphthyl)hexyl group exhibited the strongest inhibitory effect.