Synthesis and Biological Evaluation of O‐Methylated Glycolipids Related to PGLs via Direct Stereoselective Glycosidation and Sequential Suzuki–Miyaura Coupling using Boracyclane

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.