Insecticidal efficacy and persistence of a co-occluded binary mixture of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) variants in protected and field-grown tomato crops on the Iberian Peninsula.

Background: A binary co-occluded mixture (HearSP1B:LB6) of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) variants was previously found to be highly pathogenic under laboratory conditions. The insecticidal efficacy and persistence of this mixture were determined in greenhouse and field-grown tomato crops in Spain and Portugal.

Results: Concentrations of 10(9) -10(11) occlusion bodies (OBs) L(-1) of HearSP1B:LB6 resulted in 89-100% mortality of larvae on treated tomato plants in growth chambers.

Discovery of a potent, dual serotonin and norepinephrine reuptake inhibitor.

The objective of the described research effort was to identify a novel serotonin and norepinephrine reuptake inhibitor (SNRI) with improved norepinephrine transporter activity and acceptable metabolic stability and exhibiting minimal drug-drug interaction. We describe herein the discovery of a series of 3-substituted pyrrolidines, exemplified by compound 1. Compound 1 is a selective SNRI in vitro and in vivo, has favorable ADME properties, and retains inhibitory activity in the formalin model of pain behavior.

Regioselective palladium-catalyzed arylation of 4-chloropyrazoles.

A highly regioselective Pd-catalyzed arylation of N-methylpyrazoles with aryl bromides is described. This transformation was studied extensively via automated reaction screening. A Design of Experiments (DoE) approach for optimizing the critical parameters was applied, resulting in excellent conditions for preparing selectively 5-arylpyrazoles in moderate to excellent yields under mild conditions.

Palladium-catalyzed arylation and heteroarylation of azolopyrimidines.

A comparative study of the palladium-catalyzed arylation and heteroarylation of 5-bromoazolopyrimidines shows that aryl and electron-rich heteroaryl boronic acids gave higher yields than those obtained using the corresponding aryl and heteroaryl tributyl stannanes. In contrast, the reaction with electron-poor heteroaryl tributyl stannanes gave better results than the corresponding boronic acids.

Heterocyclizations with tosylmethyl isocyanide derivatives. A new approach to substituted azolopyrimidines.

An efficient synthesis of substituted azolopyrimidines such as pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidines, pyrimido[1,6-a]indoles, benzo[4,5]imidazo-[1,2-c]pyrimidines, an imidazo[1,2-c]pyrimidine, and pyrazolo[1,5-c]pyrimidines is described. The method involves the reaction of N-protected bromomethylazoles and tosylmethyl isocyanide (TosMIC) derivatives in nonanhydrous media. The study of the reaction conditions shows that the method is only successful under phase-transfer conditions (CH2Cl2/30% aq NaOH) using benzyltriethylammonium chloride as a catalyst.

Reaction of bromomethylazoles and tosylmethyl isocyanide. A novel heterocyclization method for the synthesis of the core of marine alkaloids variolins and related azolopyrimidines.

A novel and efficient synthesis of the pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine system, the heterocyclic core of the variolin family of marine alkaloids, is described. The route involves the reaction of 3-bromo-2-(bromomethyl)pyrrolo[2,3-b]pyridine and tosylmethyl isocyanide (TosMIC) under phase-transfer conditions. This unprecedented reaction was also used to synthesize a series of new methoxycarbonyl azolopyrimidines by reaction of TosMIC with bromomethylindoles, bromomethylbenzimidazole, and bromomethylpyrazole.