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

Clerodane diterpenes are a class of secondary metabolites that can be classified into four types according to the configuration of the H3-19/H-10–H3-17/H3-20 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 13C 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 CC-type 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.