Isolation and Synthesis ofN-(2-Methyl-3-oxodec-8-enoyl)-2-pyrroline and 2-(Hept-5-enyl)-3-methyl-4-oxo-6,7,8,8a-tetrahydro-4H-pyrrolo[2,1-b]1,3-oxazine – Two New Fungal Metabolites with in vivo Anti-Juvenile-Hormone and Insecticidal Activity

Abstract

Two new natural products, N-(2-methyl-3-oxodec-8-enoyl)-2-pyrroline (2) and 2-(hept-5-enyl)-3-methyl-4-oxo-6,7,8,8a-tetrahydro-4H-pyrrolo[2,1-b]-1,3-oxazine (3), have been isolated from Penicillium brevicompactum Dierckx. Compound 2 has shown an important in vivo anti-juvenile-hormone (anti-JH) activity while compound 3 has exhibited insecticidal activity against Oncopeltus fasciatus Dallas. Both products have been synthesized starting from 1,4-hexadiene, by means of a sequence of reactions which includes the preparation of 6-octenoic acid and its transformation into the corresponding acid chloride, in order to acylate Meldrum's acid. Subsequent aminolysis with pyrrolidine, followed by methylation at the activated position of the β-oxo amide with iodomethane, introduction of a methoxy group at the pyrrolidine ring by anodic oxidation and final elimination of methanol on SiO2 led to 2 and 3. The fact that both metabolites can be prepared by the same sequence indicates that they must be biogenetically related. Based on structural similarities, compounds 2 and 3 are also closely related to the recently discovered brevioxime (1).