Synthesis of 6′-acylamido-6′-deoxy-α-d-galactoglycerolipids

Aminoglycoglycerolipid 1a isolated from an algal extract showed activity against the enzyme Myt1 kinase with an IC50 value of 0.12 μg/mL. Its analogues, 6′-acylamido-6′-deoxy-α-d-galactoglycerolipids (2a–g) were synthesized in an efficient way with high stereoselectivity. The key step was to employ a 4-OAc protecting group of the galactosyl donor 14 as a remote neighboring participation group to give the glycoside with high α-anomeric selectivity (α:β = 32:1) in the glycosylation. The preliminary bioactivity screening showed that compound 2g exhibited good inhibition against Myt1 kinase.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 6′-acylamido-6′-deoxy-α-d-galactoglycerolipids 2a–g were synthesized in a concise strategy with high stereoselectivity. ► Glycosylation employing thiogalactoside donor 14 with a 4-OAc protecting group was achieved with excellent α-selectivity. ► Compound 2g showed good inhibition against Myt1 kinase.