Synthesis of all four isomers of (E)-4,5-dihydroxydec-2-enal using osmium-catalysed asymmetric dihydroxylation (original) (raw)

The enantioselective synthesis of the four possible isomers of (E)-4,5dihydroxydec-2-enal, a cytotoxic product formed in peroxidised liver microsomal lipids, is accomplished via a Sharpless AD reaction alone or associated as appropriate with a regioselective epimerisation of one of the introduced hydroxy groups. (~) 1997 Elsevier Science Ltd (E)-4,5-Dihydroxydec-2-enals la--d are cytotoxic aldehydes identified, apart from the stereochemistry, by Comporti and Esterbauer groups in liver microsomal lipids subjected to NADPH-Fe induced peroxidation, l Since these compounds are of interest in studying the damage consequent on the physiological or pathologic lipid peroxidation 2,3 and their synthesis have not been reported, we started a program to prepare them in quantities suitable for biological studies. As a result of our work we have already reported their preparation starting with a chiral pool of appropriate pentoses or of mannitol.4,5 Here we report other new, convenient and general asymmetric syntheses of the hydroxyaldehydes la-d based on a strategy of reagent-control of the stereochemistry. OH 9H OH 9H CsH1 " CHO C~H~ ~ ~" CsH OH OH OH OH 4R, 5R 4S, 5S 4~ 5R 4R, 5S la lb 1¢ ld