Total Synthesis of Phorboxazole B

An efficient and highly convergent total synthesis of the potent antitumor agent phorboxazole B has been achieved. The synthetic strategy of this synthesis features: 1) a highly efficient substrate‐controlled hydrogenation to construct the functionalized cis‐tetrahydropyrane unit; 2) iterative crotyl addition to synthesize the segment that contains alternating hydroxyl and methyl substituents; 3) Hg(OAc)2/I2‐induced cyclization to establish the cis‐tetrahydropyrane moiety; 4) 1,3‐asymmetric induction in the Mukaiyama aldol reaction to afford the stereogenic centers at C9 and C3; and 5) the exploration of the Still–Gennari olefination reaction to complete the macrolide ring of phorboxazoloe B. 21‐Membered macrolides: Ranked among the most cytostatic natural products ever known, phorboxazole B (see scheme) represents a new class of 21‐membered macrolides. Herein we report an efficient and convergent total synthesis of this compound.