The Asymmetric Synthesis Of Phenyl Glycerol Amides

The syntheses of seco-clausenamide (II) ,N-demethyl seco-clausenamide ( I ) and their N-alkylated derivatives were studied.A. Four stereoisomers (2-pairs of enantiomers) of N-de-methyl secoclausenamide (II) N-(B-phenylethyl)-phenylgly-ceramide were asymmetrically synthesized through following four routes: I, from D-mannitol. II, through Sharpless asymmetric epoxidation of cinnamyl alcohol. III, through enantio-topic dihydroxylation of cis-and trans-methyl cinnamate. IV through PLE-catalyzed resolution of methyl phenylglyce-rjnate and phenylglycidate. Their results were summerized as following:Route I. (2S,3R) - and (2S,3S)-N-(β-phenylethyl)-phenyl-glyceramides (A^- and B^-) and the N-methyl derivatives were synthesized from D-mannitol through 11 steps. The overall yield of A^- amounted to 13.2&. By careful study on every step of the route it was shortened to 7 steps end the total yield of A^- was raised to 21.1% It was found that 1,2- or 2,3-(?)-isopropylidene-3-phenylglycerol rearranged under acidic condition to give a mixture of 1,2- and 2,3-acetonidee. The ratio of 1,2-:2,3-acetonide in the mixture depends upon the stereochemistry of C₂C₃ Fquilibrated mixtures with ratio of 1:4 in favor of 2,3-acetonide for threo and 4:1 with 1,2-acetonide as the major component for erythro were given. Based upon the physical constants of (2S,3R)A^- obtained from the above preparation and ready conversion of C₂ configuration in the erythro acetonide in the ba6ic medium, the assignment of the configuration of natural product has been revised to 2R.3R.Route II. Two pairs of optical enantiomers of N-(β-phenylethyl)-phenylglyceraraide were synthesized through 6 steps via Sharpless epoxidation of trans-cinnamyl alcohol.