Isolation, Identification, and DFT-Based Conformational Analysis of Sesquikarahanadienone and Its Congeners from Freshwater Dothideomycetes Neohelicascus Aquaticus KT4120

Three unique sesquiterpenes, i.e., sesquikarahanadienone (1), sesquicarenol (2), and sesquikarahanaether (3), along with 2-chlorodiorcinol (4) and several known compounds, were isolated from freshwater Dothideomycetes Neohelicascus aquaticus KT4120. The relative structures of the new compounds 1-3 were elucidated by spectroscopic analysis. The synthesis of compound 1 confirmed its structure. Meanwhile, range - separated-hybrid-generalized-gradient-appro ximation (RSH-GGA) functionals were developed to estimate the long-range interactions appropriately. However, conformational analyses suggested that the RSH-GGA functional of co1397XD overestimated the van der Waals interaction and suggested the bent conformers of conformationally very flexible compounds 1 and 2. In contrast, the global-hybrid-GGA (GHGGA) functionals, such as B3LYP, appropriately reproduced them. The absolute configurations of 1-3 were determined by comparing experimental and calculated electronic circular dichroism (ECD) spectra. A plausible biosynthetic route for these compounds was discussed, according to which an enetype ring opening of a daucane framework gave monocyclic 1 and a disrotatory electrocylization provided the bicyclo[4.1.0]-heptane framework of 2. The latter biosynthetic process was verified through the chemical transformation of compounds 1 to 2 using potassium tert-butoxide in the presence of Nmethylmorpholine-N-oxide.