(+)-Phorboxazole A Synthetic Studies. A Highly Convergent, Second Generation Total Synthesis of (+)-Phorboxazole A

A second generation total synthesis of the potent antitumor agent (+)-phorboxazole A (1) has been achieved. The cornerstone of this approach comprises a more convergent strategy, involving late-stage Stille union of a fully elaborated C(1−28) macrocycle with a C(29−46) side chain. The second generation synthesis entails the longest linear sequence of 24 steps, with an overall yield of 4.2%.