Cyclohelminthols Y1–Y4 Metabolites Possessing Two Spirocyclopropanes in Their Structure

Cyclohelminthols Y1–Y4 ( 1 – 4 ) were isolated from the culture broth of Helminthosporium velutinum yone96. These compounds are diastereomers to each other featuring 3-azabicyclo[3.1.0]hexane-6-spirocyclopentane linked with a cyclopentanespirocyclopropane framework. Their planar structures were established via the comparison of their spectra with the simpler analogue cyclohelminthol X as well as analysis of their HMBC spectra. Although the proton-deficient core frameworks of 1 – 4 prevented us from obtaining configurational information via conventional NMR analysis, their total structures involving the relative and absolute configurations were established using density functional theory (DFT)-based molecular modeling calculations. The present study demonstrates the effectiveness of the comparison between the theoretical and experimental δ 13 C values for stereochemical analysis by focusing on the carbons that show relatively large δ 13 C deviations among the isomers. The G -ring of these molecules most likely originates from the cyclopropanation of the C6C7 double bond with the carbene equivalent 6 derived from cyclohelminthol IV ( 7 ), which was isolated from the same producer fungus. Preliminary biological experiments revealed the potent cytotoxicity of the (6 S )-isomers against COLO201 cells, whereas the (6 R )-isomers exhibited weak activity. The antifungal assay with Cochiobolus miyabeanus showed a slightly different profile.