A synthetic model for the [4+2] cycloaddition in the biosynthesis of the brevianamides, paraherquamides, and related compounds

The reactivity of model systems for the proposed [4+2] cycloaddition in the biosynthesis of tho brevianamides, paraherquamides, and marcfortines is ex plored. The model for the intermolecular reaction reveals that the cycloadd ition takes place under mild conditions only if activated, very reactive di enophiles are used. When relatively unreactive dienophiles such as cyclopen tene and cyclohexene are used, harsh reaction conditions and/or a Lewis aci d catalyst are necessary for the reaction. In contrast, the model for the i ntramolecular reaction demonstrates that the cycloaddition takes place with in a few hours at room temperature, even in the absence of a Lewis acid cat alyst. Conclusions drawn from these results are discussed in relation to th e biosynthesis of the aforementioned metabolites. (C) 2000 Elsevier Science Ltd. All rights reserved.