Structural Revision of Tinotufolins from Tinospora crispa Leaves Guided by Empirical Rules and DFT Calculations

Abstract

Clerodane diterpenes are a class of secondary metabolites that can be classified into four types according to the configuration of the H 3 -19/H-10−H 3 -17/H 3 -20 fragment, i.e., trans−cis (TC), trans−trans (TT), cis−cis (CC), and cis−trans (CT). Tinotufolins A−C and E (1a−3a and 5a), isolated from the leaves of Tinospora crispa, were previously elucidated as CT-type clerodanes; however, our established 13 C NMR-based empirical rules and density functional theory calculations suggested that these clerodanes belong to the CC type. Therefore, tinotufolins A−F (1−6) were reisolated from the leaves of T. crispa, along with an undescribed compound 7 and known compounds 8−11, and their structures were established by extensive spectroscopic analyses. The structures of tinotufolins A−C and E were revised to CCtype 1−3 and 5, and undescribed compound 7 was established as a CC-type clerodane. The present study demonstrates that empirical rules and calculations can efficiently identify and revise erroneous structures in clerodane diterpenes.