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 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 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.