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).

Insecticidal, Anti-juvenile Hormone, and Fungicidal Activities of Organic Extracts from Different Penicillium Species and Their Isolated Active Components

“…Additional experimental work has been carried out with the culture broth dichloromethane extract of P79 Penicillium brevicompactum isolate, in order to identify an active in vivo anti-JH compound. Recently, we have reported on the isolation, identification and alternative synthesis of two new natural products, N-(2-methyl-3oxodec-8-enoyl)-2-pyrroline (1) and 2-hept-5-enyl-3-methyl-4-oxo-6,7,8,8a-tetrahydro-4H-pyrrolo[2,1-b]-1,3-oxazine (2), possessing anti-JH and insecticidal activity, respectively (Cantín et al, 1999). Now, we wish to report on the biological activities of the synthesized natural products as well as their synthetic precursors.…”

Breast Cancer Migration and Proliferation Inhibitory and Antibiotic Secondary Metabolites from The Egyptian Olive Tree Endophytic Fungus Penicillium citrinum

“…[18][19][20][21] Compound 1 (50 mg) showed a UV active spot on pr-coated Si gel 60 TLC at 254 nm with no change H-3, respectively, in addition to a singlet signal at δ 8.22 assigned for the oxygenated olefinic proton H-1. The 13 C PENDANT NMR spectrum showed thirteen carbon signals, including carbon signals for three methyl groups at δ 18.6, 18.6, and 18.3 assigned for methyl groups C-9, C-10, and C-11.…”

“…Interpretations of compound 2 protons and carbons were aided by the HMQC experiment (Table 3). Comparison of NMR data of 2 with those reported in literature 19 confirmed its identity as: 2-(Hept-5-enyl)-3-methyl-4-oxo-6,7,8,8a,tetrahydro-4H-pyrrolo[2,1-b]-1,3-oxazine.…”

Catalytic Asymmetric Formal [3+2] Cycloaddition of Azoalkenes with 3-Vinylindoles: Synthesis of 2,3-Dihydropyrroles

“…2,3-Dihydropyrroles are common structural motifs that are widely present in biologically significant molecules, and they are also valuable intermediates in organic synthesis (Augeri et al, 2005;Cantín et al, 1999;Hertel and Xu, 2002;Herzon and Myers, 2005;Kawase et al, 1999;Marti and Carreira, 2005;Petersen and Nielsen, 2013). Although approaches to access racemic 2,3-dihydropyrroles are well documented (El-Sepelgy et al, 2018;Jiang et al, 2017;Liang et al, 2017Liang et al, , 2018Ma et al, 2018;Zhu et al, 2009Zhu et al, , 2011, reports on catalytic asymmetric synthesis of 2,3-dihydropyrroles are scarce.…”