CHEMOENZYMATIC SYNTHESIS OF ALL 4 STEREOISOMERS OF SPHINGOSINE FROM CHLOROBENZENE - GLYCOSPHINGOLIPID PRECURSORS

Advantageous use of homochiral cyclohexadiene-cis-1,2-diol 2, availabl e by means of biocatalytic oxidation of chlorobenzene with toluene dio xygenase, has enabled the synthesis of all four enantiomerically pure C-18-sphingosines 1. The four requisite diastereomers of azido alcohol s 4a-d were accessed by regioselective opening of epoxides 7 and 8 wit h either azide or halide ions. The configuration of C4 and C5 in azide s 4 defines the stereochemistry of the incipient sphingosine chain, li berated from 4 by the oxidative cleavage of the C1-C6 olefin. For L-th reo-sphingosine (1b), lactol 20b generated by this cleavage was concer ted by periodate oxidation to azido deoxy L-threose 22b, which gave 1b upon Wittig olefination and reduction. Similarly, D-erythro-sphingosi ne (1a) and L-erythro-sphingosine (1c) were generated from 4a,c, respe ctively. The last sphingosine (1d) was synthesized from the silyl-prot ected azido alcohol 29d. Subsequent transformations provided silyl-pro tected azido deoxy D-threose 32d, which upon Wittig olefination and re duction gave D-threo-sphingosine (1d). Experimental and spectral data are provided for all new compounds.