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

Abstract

Abstract 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-approximation (RSH–GGA) functionals were developed to estimate the long-range interactions appropriately. However, conformational analyses suggested that the RSH–GGA functional of ωB97X-D 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 (GH-GGA) 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 ene-type 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 N-methylmorpholine-N-oxide.