Pseudo-Enantiomeric Paraphaeolactones and Their Biosynthetic Derivatives from Paraphaeosphaeria sp. KT4192: A Proposition of a Favorskii Rearrangement for Their Biosynthesis.

Paraphaeolactones A1, A2, B1, and B2 ( 1 - 4 , respectively), known arthropsadiol D ( 5 ), massariphenone ( 6 ) and its positional isomer 7 , and massarilactones E ( 8 ) and G ( 9 ) were isolated from the culture broth of Paraphaeosphaeria sp. KT4192. Although the structural resemblance between 1 and 2 implies that these comprised a diastereomeric pair at the C-2 stereogenic center, electronic circular dichroism (ECD) spectral analyses revealed that they were pseudo-enantiomers possessing the common (2 R )-configuration. Paraphaeolactones B1 and B2 ( 3 and 4 ) were the derivatives of 2 , which equipped the 3-(1-hydroxy-2-oxopropyl)-4-methylcatechol moiety via an acetal bond at C-10. The relative configurations of their acetal carbons were elucidated by NOE experiments, and those of C-8' were deduced independently by ECD spectral analysis. The present study disclosed that 1 - 5 , 8 , and 9 contain a methylcyclohexene substructure with the same absolute configuration. This prompted us to reinvestigate the absolute configurations of known structurally related fungal metabolites, allowing us to conclude that the methylcyclohexene moieties of these natural products have the same absolute configuration despite the variety of configurations of other stereogenic centers. The plausible biosynthetic routes for 1 - 9 are discussed on the basis of the above conclusion. We propose a Favorskii rearrangement as the key transformation for biosyntheses of 1 - 4 .