Microbial diversification of Diels–Alder cycloadducts by whole cells of Penicillium brasilianum

Abstract

Functionalizations of cycloadducts are important steps for the use of Diels-Alder reactions in the construction of complex cyclic or polycyclic molecules from relatively simple starting materials. In the present work, we studied the ability of Penicillium brasilianum to perform microbial transformations of racemic Diels-Alder endo-cycloadducts. Thus, Diels-Alder products, obtained from reacting cyclopentadiene or 2,3-dimethylbutadiene with alkylated para-benzoquinones, were transformed by the resting cells of P. brasilianum producing new functionalized polycyclic compounds. These biotransformations yielded novel products of oxidation and ring closure, reduction of the C=C or C=O in [Formula: see text]-unsaturated system, and allylic hydroxylations. The reduction products (conjugated double bond and carbonyl group) were also synthesized, and the enantioselectivity of both in vitro and in vivo processes was evaluated. In all cases, the microbiological transformations were enantioselective. In silico docking studies of the Diels-Alder cycloadducts with P. brasilianum oxidoreductase "old yellow enzymes" shed more light on these transformations.

Insights into Penicillium brasilianum Secondary Metabolism and Its Biotechnological Potential

“…The microbial diversification of racemic Diels–Alder endo-cycloadducts by whole cells of Penicillium brasilianum was recently demonstrated by Din and co-workers [ 79 ]. The authors described the use of P. brasilianum as a catalyst in order to induce the biotransformation of Diels-Alder endo-cycloadducts obtained from the reaction of the dienes, cyclopentadiene and 2,3-dimethylbutadiene with para -benzoquinones.…”

“…The experiments resulted in 15 biotransformed products, being eight of them novel terpene analogs. The fungus was able to perform oxidation and ring closure reactions, reduction of the C=C or C=O in α,β-unsaturated system, and allylic hydroxylations [ 79 ].…”