Isolation, structural assignment, and synthesis of N-(2-methyl-3-oxodecanoyl)-2-pyrroline, a new natural product from Penicillium brevicompactum with in vivo anti-juvenile hormone activity

A new natural product with in vivo anti-juvenile hormone (JK) activity, N-(2-methyl-3-oxodecanoyl)-2-pyrroline (2), has been isolated from Penicillium brevicompactum Dierckx. Its structure has been tentatively assigned based on spectral data and unambiguously confirmed by alternative syntheses. Compound 2 has been prepared by means of a sequence of reactions beginning with acylation of Meldrum's acid by octanoyl chloride. The subsequent steps have been aminolysis of the resultant intermediate with pyrrolidine,;alkylation of the active position with iodomethane, introduction of a methoxy group in the pyrrolidine ring by anodic oxidation, and final elimination of methanol through adsorption on SiO2 and heating. The natural product 2 and its bicyclic isomer 2-heptyl-3-methyl-4-oxo-6,7,8,8a-tetrahydro-4H-pyrrolo [2,1-b]-1,3-oxazine (3) are also obtained. This reveals that 2 can be biogenetically related to the recently discovered brevioxime (1). Compound 2 and the synthetic precursors of 2 have shown important biological activities as insecticides (against Oncopeltus fasciatus Dallas) and fungicides. The natural product induces precocious metamorphosis in the target insect (70% precocious adults at 10 mu g/nymph). In view of the above results, these products could be useful as lead molecules for the synthesis of analogues with enhanced biological activities.