Synthesis of tricalysiolides using cafestol as a renewable source

Cafestol (1) is a diterpene derived from coffee grounds that serves as a valuable precursor for the synthesis of structurally complex natural products. Continuing our studies on the synthesis of tricalysiolide B (3) via Pinnick oxidation, herein we explore new synthetic strategies to access tricalysiolides E (5) and F (6), complex diterpenoids with promising biological activities. In this context, we performed a dehydration reaction using Burgess reagent to access the intermediate 4 from 2 in 83% yield. A central challenge in this project lies in the allylic C1-oxidation of 4 to access tricalysiolide F (6) selectively. Subsequently, this study focuses on the hydrolysis of tricalysiolide diacetates, as the conjugated system of these complex structures makes it difficult to prevent ring-opening of the lactone. Given that these intricate frameworks are often difficult to access, these platforms represent attractive targets for the development of innovative synthetic methodologies.