A Refined Synthetic Approach to the Cyclopentane Unit of Highly Oxygenated Jatrophane Diterpenes

Abstract:

Jatrophane diterpenes represent a structurally intricate family of macrocyclic diterpenoids characterized by a highly oxygenated framework and diverse biological properties, including Pglycoprotein modulation and anti-inflammatory activity. Their densely functionalized [5+12] bicyclic core and multiple stereocenters pose significant synthetic challenges, prompting continued interest in efficient chemical access to these molecules and related analogues. In this study, we describe our synthetic efforts toward the cyclopentane unit, i.e., the five-membered core of jatrophanes, as a key intermediate, guided by retrosynthetic analysis. The target cyclopentane segment was synthesized in nine steps from TBSO(CH2)3-COOH in an overall 24% yield. Key features of the synthesis include an anti-selective Evans aldol reaction and a ring-closing metathesis/selective hydrogenation sequence, which enabled the construction of the densely functionalized cyclopentane framework. These results provide a practical foundation for the total synthesis of the target jatrophane diterpene and for the preparation of its derivatives.