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).

Novel Inhibitors of the Mitochondrial Respiratory Chain: Oximes and Pyrrolines Isolated fromPenicillium brevicompactumand Synthetic Analogues

“…It is worth noticing that neither 5a nor 3a inhibited the respiratory chain of mammalian cells while, according to previous assays (8,11,12), 5a is able to prevent spontaneous juvenile hormone synthesis in vitro and 3a shows antijuvenile hormone in vivo activity. This would make these compounds very promising for future application in pest control fields, because they would not induce damage in mammalian mitochondria.…”

“…Recently, the isolation of brevioxime (5a) and other bioactive metabolites from the P. breVicompactum culture broth has been reported (8). During the chemical synthesis of these compounds in order to confirm their structures, a number of intermediates showing interesting insecticidal and fungicidal activities were obtained (Figure 1) (8)(9)(10)(11)(12)(13)(14). The important nature of these compounds has encouraged other research groups to synthesize 5a and other analogues (15)(16)(17)(18)(19)(20).…”

“…In the past years, a new series of natural and synthetic products with important biological activities have been described as inhibitors of mitochondrial respiratory chain complex I (NADH oxidase activity) (3)(4)(5)(6)(7). In this context, it has been studied here whether the oxime 5a (a mixture of E And Z-oxime) and two natural analogues from P. breVicompactum, 3a (11) and 3b (9), as well as 13 synthetic analogues [three new pairs of diastereomers 1c′/1c′′, 3c′/3c′′, and 4c′/4c′′, oxime 5c, and six already known compounds 5b (16), 6 (13), and 7-10 (10)], could be new inhibitors of the respiratory chain and more specifically which complexes in the chain were affected (Figure 1).…”

Multifunctional cytochrome P450 orchestrates radical cleavage and non-radical cyclization in 5-oxaindolizidine biosynthesis

“…Given the taxonomic specificity of penicilactam A ( 1 ) production in Penicillium species, 1,3,4,8,29 we systematically screened 56 Penicillium strains under varied cultivation conditions. LC-MS profiling identified the halophyte -derived Penicillium citrinum HDN11-186 as a potental producer of 1 ( m / z 250.1799 [M + H] + ) (Fig.…”

Exploring the Extracellular Macromolecular Composition of Crude Extracts of Penicillium rubens Strain 212 for Elucidation Its Mode of Action as a Biocontrol Agent

“…Cantín et al [ 77 , 78 ] isolated and identified N -(2-methyl-3-oxodecanoyl)-2-pyrroline from the culture medium of Penicillium brevicompactum , which the authors relate to in vivo anti-juvenile hormone activity [ 79 ]. The antioomycete activity of several Metarhizium extracts was also associated with previously isolated aurovertins, fungerin, N -(methyl-3-oxodec-6-enoyl)-2-pyrroline, and N -(methyl-3-oxodecanoyl)-2-pyrroline [ 80 ].…”