Synthesis of glycoglycerolipid of 1,2-dipalmitoyl-3-(N-palmitoyl-6′-amino-6′-deoxy-α-d-glucosyl)-sn-glycerol and its analogues, inhibitors of human Myt1-kinase

A glycoglycerolipid 1a isolated from a marine alga showed inhibition to Myt1 kinase with IC50 of 0.12 μg/mL. We synthesized 1a and its seven analogues (1b–h) in an efficient method with high stereoselectivity. The process employed trichloroacetimidate donor 4b at low substrate concentration to achieve high α-selectivity (α/β = 33:1) in glycosylation reaction. The present synthesis provided various acyl derivatives required for the study on the structure–activity relationship later.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Glycosylation of (S)-isopropylideneglycerol with donors thioglycoside 4a and trichloroacetimidate 4b was examined. ► Glycosylation employed trichloroacetimidate donor 4b at low concentration achieved excellent α-selectivity. ► The natural aminoglycoglycerolipid 1a and its seven analogues were synthesized in a concise strategy with high stereoselectivity.