Total synthesis of (+)-phorboxazole A exploiting the Petasis-Ferrier rearrangement

A highly convergent, stereocontrolled total synthesis of the potent antipro liferative agent (+)-phorboxazole A (1) has been achieved. Highlights of th e synthesis include: modified Petasis-Ferrier rearrangements for assembly o f both the C(11-15) and C(22-26) cis-tetrahydropyran rings; extension of th e CP Julia olefination to the synthesis of enol ethers; the design, synthes is, and application of a novel bifunctional oxazole linchpin; and Stille co upling of a C(28) trimethyl stannane with a C(29) oxazole triflate. The lon gest linear sequence leading to (+)-phorboxazole A (1) was 27 steps, with a n overall yield of 3%.