UC Berkeley

The ophiobolin sesterterpenes are notable plant pathogens which have recently elicited significant chemical and biological attention because of their intriguing carbogenic frameworks, reactive functionalities, and emerging anticancer profiles. In Chapter 1, a 14-step total synthesis of (+)-6-epi-ophiobolin A is disclosed. This work demonstrates a streamlined synthetic platform to complex ophiobolins from (–)-linalool by leveraging the disparate termination modes of a radical polycyclization cascade for divergent elaboration and functionalization.

In Chapter 2, the synthetic studies toward the polycyclic norcembranoid diterpene natural product ineleganolide is described. The synthetic strategy employs a Liebeskind-Srogl coupling to unite (–)-linalool- and (–)-perillaldehyde-derived fragments followed by sequential Ueno-Stork radical cyclization and intramolecular etherification to forge the 5,5,5,6 tetracyclic core of ineleganolide. Subsequent efforts to construct the pentacyclic core of ineleganolide are disclosed. Efforts to advance the late-stage intermediate to the natural product are currently ongoing.