HIGHLY STEREOCONTROLLED TOTAL SYNTHESIS OF LEUKOTRIENE-B4, 20-HYDROXYLEUKOTRIENE-B4, LEUKOTRIENE-B3, AND THEIR ANALOGS

A highly stereocontrolled and practical new method for synthesis of LTB4 (1), 20-OH-LTB4 (2), and LTB3 (3) has been developed, which uses the palladium-catalyzed coupling reaction of the vinylborane 5, derived from the C(l)-C(9) fragment 4, with the corresponding C(10)-C(20) fragments 6a-c. The acetylene 4 was synthesized by palladium-copper-catalyzed coupling reaction of (trimethylsilyl)acetylene with the bromide 12, which was prepared from y- (trimethylsilyl)allylic alcohol (S)-10 by bromination followed by debromosilylation. The alcohol (5)–10 was obtained by the kinetic resolution of the racemate dl-10 using the Sharpless reagent. The vinyl iodides 6a and 6b were prepared from racemic y-(trimethylsilyl)allylic alcohols dl-17 and dl-28, respectively, by the Sharpless kinetic resolution followed by the reactions taking advantage of the reactivity of vinylsilane moiety, while the segment 6c was prepared by the Sharpless kinetic resolution of racemic y-iodoallylic alcohol dl-34 followed by protection. By using this method, precursors of the radiolabeled LTB4 and 20-OH-LTB4, i.e., 14,15-didehydro-LTB4 (40) and 14,15-didehydro-20-OH-LTB4 (41), respectively, were also synthesized. Similarly the novel structural analogues of LTB 42–44 were prepared. © 1990, American Chemical Society. All rights reserved.