Alternative synthetic approach for (+)-phomopsidin via the highly stereoselective TADA reaction

This manuscript describes an alternative synthetic approach for (+)-phomopsidin, which shows strong inhibitory activity against the assembly of microtubule proteins. We observed that the TADA reaction of the macrolactone 5 with the reversed C11 configuration provided the desired cycloadduct 6 in 86% yield with excellent stereoselectivity (dr=16:1). Luche reduction of the ketone derived from the major product of the TADA reaction resulted in a 91% yield with excellent stereoselectivity (dr=21:1), and the major product was successfully converted to the known compound in the previously reported total synthesis of (+)-phomopsidin, thereby accomplishing the formal total synthesis of (+)-phomopsidin.