- Chemoenzymatic synthesis of D-erythro-C18- and L-threo-C18-sphingosines
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Biocatalytic conversion of chlorobenzene to the corresponding homochiral cyclohexadiene cis-diol allows, through careful symmetry-based planning, the stereodivergent synthesis of two sphingosine stereoisomers, the natural isomer 1 and the L-threo isomer 2, from selectively prepared diastereomers of azido alcohol 5.
- Hudlicky,Nugent,Griffith
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- Chemoenzymatic Synthesis of All Four Stereoisomers of Sphingosine from Chlorobenzene: Glycosphingolipid Precursors
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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 C18-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-thereo-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-erythrosphingosine (1a) and L-erythro-sphingosine (1c) were generated from 4a,c, respectively. The last sphingosine (Id) was synthesized from the silyl-protected azido alcohol 29d. Subsequent transformations provided silyl-protected azido deoxy D-threose 32d, which upon Wittig olefmation and reduction gave D-threo-sphingosine (1d). Experimental and spectral data are provided for all new compounds.
- Nugent, Thomas C.,Hudlicky, Tomas
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p. 510 - 520
(2007/10/03)
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