Preparative syntheses of 2,6-dideoxy-α- L- lyxo-hexose (2-deoxy-α- L-fucose) and its D- ribo epimer (digitoxose)

Abstract

Methyl 4,6- O-benzylidene-2-deoxy-α- D- ribo-hexopyranoside ( 1) is converted into methyl 3,4-di- O-benzoyl-6-bromo-2,6-dideoxy-α- D- ribo-hexopyranoside ( 3) via the 3- O-benzoyl derivative ( 2) of 1 by subsequent treatment with N-bromosuccinimide. Compound 3 is the key intermediate in high-yielding, preparative syntheses of the title dideoxy sugars, which are constituents of many antibiotics. Dehydrohalogenation of 3 affords the 5,6-unsaturated glycoside 7. which undergoes stereospecific reduction by hydrogen with net inversion at C-5 to give methyl 3,4-di- O-benzoyl-2,6-dideoxy-β- L- lyxo-hexopyranoside ( 8), whereas reductive dehalogenation of 3 provides the corresponding D- ribo derivative 4. The unprotected glycosides 9 ( L- lyxo) and 5 ( D- ribo) are readily obtained by catalytic transesterification, and mild, acid hydrolysis gives the crystalline title sugars 10 ( L- lyxo) and 6 ( D- ribo) in 45 and 57% overall yield from 1 without the necessity of chromatographic purification at any of the steps.