Chemoenzymatic Synthesis of All Four Stereoisomers of Sphingosine from Chlorobenzene: Glycosphingolipid Precursors(1)(a).

ABSTRACT

Advantageous use of homochiral cyclohexadiene-cis-1,2-diol 2, available by means of biocatalytic oxidation of chlorobenzene with toluene dioxygenase, has enabled the synthesis of all four enantiomerically pure C(18)-sphingosines 1. The four requisite diastereomers of azido alcohols 4a-d were accessed by regioselective opening of epoxides 7 and 8 with either azide or halide ions. The configuration of C4 and C5 in azides 4 defines the stereochemistry of the incipient sphingosine chain, liberated from 4 by the oxidative cleavage of the C1-C6 olefin. For L-threo-sphingosine (1b), lactol 20b generated by this cleavage was converted by periodate oxidation to azido deoxy L-threose 22b, which gave 1b upon Wittig olefination and reduction. Similarly, D-erythro-sphingosine (1a) and L-erythro-sphingosine (1c) were generated from 4a,c, respectively. The last sphingosine (1d) was synthesized from the silyl-protected azido alcohol 29d. Subsequent transformations provided silyl-protected azido deoxy D-threose 32d, which upon Wittig olefination and reduction gave D-threo-sphingosine (1d). Experimental and spectral data are provided for all new compounds.