A Modular Synthesis of Antitumor Macrolide (–)‐Lasonolide A^†

Abstract

Summary of main observation and conclusion Lasonolide A was identified as a potent antitumor macrolide towards various cancer cell lines. The two tetrahydropyrans bearing multiple stereogenic centers as well as the polyene linkage attracted a dozen synthetic research groups to launch the total synthesis. Based on the synthetic methods developed in our group, namely, the hydroboration of allene and its subsequent allylation as well as the iterative hydroboration of allene and oxidation, the polyol subunits were efficiently constructed and then integrated into the final target. A new Julia olefination reagent, double‐headed sulfone, was designed to promote the rapid coupling of two aldehydes bearing multiple functional groups to secure the whole carbon framework. Another highlight of our approach is the application of a traceless protecting group, 9‐BBN (9‐borabicyclo[3.3.1]nonane), to hide the secondary alcohol for debenzylation, and for the first time, to mask the carboxylic acid for Julia olefination under strong basic conditions.