3-HYDROXYLEUKOTRIENE B-4(3-OH-LTB(4)) - TOTAL SYNTHESIS AND STEREOCHEMICAL ASSIGNMENT

The asymmetric total synthesis of 3-hydroxyleukotriene B-4 (3-OH-LTB(4 )), an ethanol-inducible proinflammatory autacoid, was achieved using a triply convergent strategy for the sequential union of propargylic a rsonium salt 3 with pyranosides 2a,b and furanose 4. Both saccharide s ubunits were derived from commercial 2-deoxy-D-ribose. The key transfo rmation involved palladium-mediated coupling of bromoacetylenide 9 wit h stannylglycal 6a,b. Subsequent Rieke zinc hydrogenation of acetylene 10a,b and controlled ionic reduction of the cross-conjugated cyclic e nol ether using NaBH3CN at pH similar to 4-4.5 established the cis-Del ta(6,7)-olefin and C(5)-hydroxyl stereochemistry, respectively, and le d to 11a,b. Methyllactol hydrolysis, PCC oxidation, methanolysis, and desilylation afforded 3(R)- and 3(S)-OH-LTB(4) methyl esters, respecti vely. On the basis of chromatographic and mass spectral comparisons, e nzymatically derived 3-OH-LTB(4) is composed principally of the 3(S)-i somer (>95%).