Total synthesis of bryostatin 2

The total synthesis of the marine macrolide bryostatin 2 is described. The synthesis plan relies on aldol and directed reduction steps in order to con struct the anti-1,3-diol array present in each of the principal subunits (A , B, and C). These fragments were coupled using a Julia olefination and sub sequent sulfone alkylation. A series of functionalization reactions provide d a bryopyran seco acid, which was macrolactonized under Yamaguchi conditio ns. Installation of the two enoate moieties took advantage of asymmetric ph osphonate and aldol condensation strategies. Reduction of the C-20 ketone a nd simple protecting group operations then completed the synthesis of bryos tatin 2. This flexible approach should provide access to a series of new an alogues of this clinically important marine natural product.