Condensation of D-mannosaldehyde derivatives with ethyl diazoacetate. An easy and stereoselective chain elongation methodology for carbohydrates: Application to new syntheses for KDO and 2-deoxy-β-KDO

Article abstract of DOI:10.1016/S0040-4020(97)00056-2

(3R and 3S) β-Hydroxy-α-diazocarbonyl compounds 4 (100%, 3:2), 9 (35%, 100:0), 14 (74%, 7:2) and 18 (100%, 100:0), prepared from 2,3,4,5,6-penta-O-acetyl-(3), penta-O-benzyl- (8), 2,3:5,6-di-O-isopropylidene-4-O-(tert-butyldimethylsilyl)- (13), and 2,3:5,6-di-O-isopropylidene-4-O-acetyl-D-mannosaldehyde (17), respectively, were acetylated, and the resulting β-3cetoxy-α-diazocarbonyl compounds treated with rhodium diacetate to give the corresponding α-enol esters, 6 (100%). 11 (35%), 16 (100%) and 20 (100%) which are potentially α-keto eaters. Molecular mechanics calculations were used in order to justify the stereoselectivity observed in the initial addition process: The problematic removal of the projecting groups from the α-enol esters is discussed. Finally, hydrazinolysis of the a-enol acetates (to quench the labile resulting α-keto ester as the corresponding and less reactive hydrazines), mild oxidation to the corresponding α-diazoesters, deprotection, and final oxidation of the diazo group with m-chloroperbenzoic acid, gave KDO in good yield. Intermediate products were used in the completely stereoselective synthesis of 2-deoxy-β-KDO, a potent inhibitor for CMP-KDO synthetase.