Synthesis of all four stereoisomers of 5-formyl-4-hydroxymethyl-1,3-oxazolidin-2-ones from d-glucosamine

• Synthesis of all four stereoisomers of 5-formyl-4-hydroxymethyl-1,3-oxazolidin-2-ones.
• Regioselective cyclization of N-phenoxycarbonyl-d-glucosamine to the 2-N,3-O-carbonyl-derivative.
• 2-N,3-O-Carbonyl-d-glucosamine could epimerize to d-mannosamine derivative.
• 4,5-cis-5-Formyl-4-hydroxymethyl-oxazolidones form five-membered lactol ring.
• 4,5-trans-5-Formyl-4-hydroxymethyl-oxazolidones mainly form methanol adduct of the aldehyde.

All four stereoisomers of 5-formyl-4-hydroxymethyl-1,3-oxazolidin-2-ones (FHOs) were conveniently prepared from d-glucosamine by base-catalyzed epimerizations. 2-N,3-O-Carbonyl-d-glucosamine (7) was successively treated with NaBH4 and NaIO4 to give (4S,5R)-FHO 18, which was epimerized with DBU in DMF to give (4S,5S)-FHO 20. The glucosamine derivative 7 was epimerized to 2-N,3-O-carbonyl-d-mannosamine 23, from which (4R,5R)- and (4R,5S)-FHO derivatives (27 and 31) were prepared. The NMR measurements revealed that the 4,5-cis-4(or 5)-formyl-5(or 4)-hydroxymethyl-oxazolidinone derivatives form five-membered lactol ring, whereas the 4,5-trans-disubstituted derivatives form the hydrate or methanol adduct of the open-chain aldehyde, or the symmetrical dimer.

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