Asymmetric Total Synthesis of (+)-Didemniserinolipid B via Achmatowicz Rearrangement/Bicycloketalization

Abstract

A new synthetic strategy was developed for the asymmetric total synthesis of (+)-didemniserinolipid B in 19 linear steps, featuring a highly efficient and enantioselective construction of 6,8-dioxabicyclo[3.2.1]octane (6,8-DOBCO) framework via a rarely explored Achmatowicz rearrangement/bicycloketalization strategy. In addition, the first total synthesis of the proposed (+)-didemniserinolipid C was accomplished with 41.6% yield in 4 steps from a common advanced intermediate 18, and a possible revised structure of (+)-didemniserinolipid C was proposed. The new convergent synthetic strategy greatly expedites the entry to the didemniserinolipids and their analogues for biological activity evaluation.