On the formation of quinoline alkaloids in plants. 4. Concerning the mechanism of cyclopenase activity

Abstract

Cyclopenase, an enzyme from the mycelium of Penicillium viridicatum Westling and Penicillium cyclopium Westling catalyses the transformation of the benzodiazepine derivatives (–)‐cyclopenine and (–)‐cyclopenol to the quinoline derivatives viridicatine and viridicatol, respectively. This rearrangement, which is connected with the elimination of molar amounts of CO2 and methylamine takes place in an nonenzymatic process too, if (–)‐cyclopenine and (–)‐cyclopenol are treated with acids or Lewis acids. In anhydrous medium instead of CO2 and methylamine, methylisocyanate is obtained. 14CO2 is formed from (–)‐[5‐14C]cyclopenine either by the enzyme or by the acid‐catalysed transformation, the viridicatine being inactive (Table). In experiments with 2H2O or H218O as solvents neither the cyclopenase nor the acid‐catalysed rearrangement proceeded with a significant incorporation of 2H or 18O (Fig. 1).These experimental results indicate that:a) enzymatic and nonenzymatic transformations of the investigated benzodiazepines to the corresponding quinoline derivatives proceed by similar mechanisms,b) closure of the hetero‐ring of the quinoline moiety involves C‐atoms 5a and 10 of the benzodiazepine compounds andc) the hydroxyl group in position 3 of the quinoline ring is derived directly from the epoxide oxygen.In Scheme 1 a possible reaction sequence for the transformation is given.