Glycosylated vinyl ethers by the Julia–Lythgoe–Kocienski olefination: application to the synthesis of 2′,5′-dideoxydisaccharides and carbohydrated β-lactams

α-Carbohydrated pyridinyl sulfones, prepared from commercially available d-(−)-ribose, d-(+)-galactose, and d-(+)-glucose through a five-step sequence, have been employed in the Julia–Lythgoe–Kocienski olefination with aldehydes. This one-pot protocol, using solid KOH at room temperature, affords the corresponding glycosidic enol ethers in moderate to excellent yields and (E)-stereoselectivities. These glycosylated adducts undergo hetero-Diels–Alder reactions with 2-formyl-1-malondialdehyde to afford 2′,5′-dideoxygenated disaccharides in good yields and complete regio- and endo-selectivity. Alternatively, the [2+2]-cycloaddition reaction of the glycosidic enol ethers with chlorosulfonyl isocyanate provided glycosylated β-lactams regioselectively and with only trans-stereoselectivity. The β-lactams could be converted to N-methylthio derivatives which show decent antibacterial activity toward methicillin-resistant strains of Staphylococcus aureus.

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(3S,4R)-4-((3aR,5R,6S,6aR)-5-((R)-1,2-bis(benzyloxy)ethyl)-tetrahydro-2,2-dimethylfuro[2,3-d][1,3]dioxol-6-yloxy)-1-(methylthio)-3-phenylazetidin-2-oneC33H37NO7S[α]D18=-7.6 (c 0.5, CH2Cl2)