Phenoxy radical coupling reactions are widely used in nature for the synthesis of
complex molecules such as lignin. Their use in the laboratory has great potential
for the production of high value compounds from the polyphenol family. While
the enzymes responsible for the generation of the radicals are well known, the
behavior of the latter is still enigmatic and difficult to control in a reaction flask.
Previous work in our laboratory using the enzymatic secretome of B. cinerea
containing laccases has shown that incubation of stilbenes leads to dimers, while
incubation of phenylpropanoids leads to dimers as well as larger coupling
products. Building on these previous studies, this paper investigates the role
of different structural features in phenoxy radical couplings. We first demonstrate
that the presence of an exocyclic conjugated double bond plays a role in the
generation of efficient reactions. In addition, we show that the formation of
phenylpropanoid trimers and tetramers can proceed via a decarboxylation
reaction that regenerates this reactive moiety. Lastly, this study investigates
the reactivity of other phenolic compounds: stilbene dimers, a dihydrostilbene,
a 4-O-methyl-stilbene and a simple phenol with the enzymatic
secretome of B. cinerea. The observed efficient dimerization reactions
consistently correlate with the presence of a para-phenol conjugated to an
exocyclic double bond. The absence of this structural feature leads to variable
results, with some compounds showing low conversion or no reaction at all. This
research has allowed the development of a controlled method for the synthesis
of specific dimers and tetramers of phenylpropanoid derivatives and novel
stilbene derivatives, as well as an understanding of features that can promote
efficient radical coupling reactions.