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 I₂ and nBu₄NOTf resulted in their activation under low temperature and provided the α-rhamnosides with excellent α-selectivity. nBu₄NOTf 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.