American Chemical Society
ja011604l_si_002.pdf (1.62 MB)

Total Synthesis of (+)-Phorboxazole A Exploiting the Petasis−Ferrier Rearrangement

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journal contribution
posted on 2001-10-13, 00:00 authored by Amos B. Smith, Kevin P. Minbiole, Patrick R. Verhoest, Michael Schelhaas
A highly convergent, stereocontrolled total synthesis of the potent antiproliferative agent (+)-phorboxazole A (1) has been achieved. Highlights of the synthesis include:  modified Petasis−Ferrier rearrangements for assembly of both the C(11−15) and C(22−26) cis-tetrahydropyran rings; extension of the Julia olefination to the synthesis of enol ethers; the design, synthesis, and application of a novel bifunctional oxazole linchpin; and Stille coupling of a C(28) trimethyl stannane with a C(29) oxazole triflate. The longest linear sequence leading to (+)-phorboxazole A (1) was 27 steps, with an overall yield of 3%.