Naphthol radical couplings determine structural features and enantiomeric excess of dalesconols in Daldinia eschscholzii

Understanding how simple molecules are pieced together in organisms may aid biotechnological manipulation and synthetic approaches to complex natural products. The mantis-associated fungus Daldinia eschscholzii IFB-TL01 produces the unusually structured immunosuppressants (±)-dalesconols A and B, along with their congener (±)-dalesconol C, with the (−)-enantiomers in excess. Here we report that these structural and stereochemical peculiarities of dalesconols A–C are a result of promiscuous and atropselective couplings of radicals derived from 1,3,6,8-tetrahydroxynaphthalene, 1,3,8-trihydroxynaphthalene and 1,8-dihydroxynaphthalene. The observed (−)-enantiomeric excess is found to depend on the dominance of particular conformers of naphthol dimer intermediates, which are ligands of laccase. The dalesconol natural products are biosynthesised in an enantiomeric excess of 67%, rather than as a single enantiomer or a racemate. Tan et al . report that this unusual enantioselectivity is a result of the dominance of particular conformers of naphthol dimer intermediates.