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-BETA-KDO

(3R and 3S) beta-Hydroxy-alpha-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), di-O-isopropylidene-4-O -(tert-bulyldimethylsilyl)- (13). and ,6-di-0-isopropylidene-4-0-acety l-D-mannosaldehyde (17), respectively, were acetylated, and the result ing beta-ncetoxy-alpha-diazocarbonpl compounds treated with rhodium di acetate to give the corresponding-alpha-enolesters,6 (100%). 11 (35%), 16(100%)and 20 (100%),which are potentially alpha-ketoesiers. Molecul armechanics calculations were used ill order to justify the stereosele ctivity observed ill the initial addition process. The problematic rem oval of the protecting groups from the alpha-keto esters is discussed. Finally, hydrazinolysis oi: the cc-enol acetates (to quench the labil e resulting a-keto ester as the corresponding and less reactive hydraz ines), mild oxidation to the corresponding alpha-diazoesters. deprotec tion, and final oxidation of the diazo group with m-chloroperhenzoic a cid, gave KDO ill good yield. Intermediate products were used ill the completely stereoselective synthesis of 2-deoxy-beta-KDO, a potent inh ibitor for CMP-KDO synthetase. (C) 1997 Published by Elsevier Science Ltd.