Zuoquan Wang

Synthesis and bioassay of improved mosquito repellents predicted from chemical structure

Mosquito repellency data on acylpiperidines derived from the U.S. Department of Agriculture archives were modeled by using molecular descriptors calculated by CODESSA PRO software. An artificial neural network model was developed for the correlation of these archival results and used to predict the repellent activity of novel compounds of similar structures. A series of 34 promising N-acylpiperidine mosquito repellent candidates (4a–4q′) were synthesized by reactions of acylbenzotriazoles 2a–2p with piperidines 3a–3f. Compounds (4a–4q′) were screened as topically applied mosquito repellents by measuring the duration of repellency after application to cloth patches worn on the arms of human volunteers. Some compounds that were evaluated repelled mosquitoes as much as three times longer than N,N-diethyl-m-toluamide (DEET), the most widely used repellent throughout the world. The newly measured durations of repellency were used to obtain a superior correlation equation relating mosquito repellency to molecular structure.

Novel Carboxamides as Potential Mosquito Repellents

ABSTRACT A model was developed using 167 carboxamide derivatives, from the United States Department of Agriculture archival database, that were tested as arthropod repellents over the past 60 yr. An artificial neural network employing CODESSA PRO descriptors was used to construct a quantitative structure-activity relationship model for prediction of novel mosquito repellents. By correlating the structure of these carboxamides with complete protection time, a measure of repellency based on duration, 34 carboxamides were predicted as candidate mosquito repellents. There were four additional compounds selected on the basis of their structural similarity to those predicted. The compounds were synthesized either by reaction of 1-acylbenzotriazoles with secondary amines or by reaction of acid chlorides with secondary amines in the presence of sodium hydride. The biological efficacy was assessed by duration of repellency on cloth at two dosages (25 and 2.5 µmol/cm2) and by the minimum effective dosage to prevent Aedes aegypti (L.) (Diptera: Culicidae) bites. One compound, (E)-N-cyclohexyl-N-ethyl-2-hexenamide, was superior to N,N-diethyl-3-methylbenzamide (deet) at both the high dosage (22 d versus 7 d for deet) and low dosage (5 d versus 2.5 d for deet). Only one of the carboxamides, hexahydro-1-(1-oxohexyl)-1H-azepine, had a minimum effective dosage that was equivalent or slightly better than that of deet (0.033 µmol/cm2 versus 0.047 µmol/cm2).

Novel and convenient routes to substituted pyrroles and imidazoles

Abstract S-Melhyl N-(benzotriazol-1-ylmethyl)thioimidate 6 is obtained by lithiation of the corresponding N-(benzotriazol-1-ylmelhyl) thioamide 5 and subsequent reaction with methyl iodide. Derivative 6 undergoes [2 + 3] cycloaddition reactions with α,β-unsaturated -esters, -ketones and -nitriles, and vinylpyridines which are followed by elimination of benzotriazole and the thioalkoxy group, to give 2,3,4-trisubstituted pyrroles. Lithiaiion of 6 followed by reactions with imines gives cyclized 4,5-dihydroimidazoles 14 which upon further treatment with ZnBr2 or direct refluxing in toluene yield the 1,25-trisubstituted imidazoles 15 in good yields.

Synthesis and characterization of a redox-active ion channel supporting cation flux in lipid bilayers.

The synthesis, cation binding and transmembrane conductive properties of a novel synthetic ion channel containing a redox-active ferrocene unit are described. Fluorescence spectroscopy was used to demonstrate that the channel supports multiple ion coordination and association constants for 1:1 and 1:2 (channel:cation) coordination for both Na(+) and K(+) were evaluated. Experiments using a black lipid membrane preparation revealed that this compound functioned effectively as an ion channel for both Na(+) and K(+). Concomitant (23)Na NMR spectroscopy studies supported this finding and revealed a Na(+) flux, at least 5 times higher than ion transport rates by monensin. Furthermore, oxidation of the redox-active centre (Fe(2+) to Fe(3+)) effectively inhibited ion transport.

A novel cyclization to isoxazolo[3,4-e][2,1]benzisoxazole

Methylation of 2,1-benzisoxazole 4,5-dione 4-oxime 2 using dimethyl sulfate in DMF and in the presence of potassium carbonate gave a substantial yield of isoxazolo[3,4-e][2,1]benzisoxazole 4 by an unexpected cyclization reaction of the O-methylation product 3.

Synthesis of Heterocyclic Ylids as Candidates for Energetic Materials

Concise syntheses of nitrogen-rich pyridinium and 1,2,4-triazolium N-imides are reported. Substrate scope and various imide-stabilizing electron withdrawing groups are examined. Energetic properties of the target molecules were studied by heats of combustion.

AN UNEXPECTED FORMATION OF DIETHYL TRANS-2,3- PIPERAZINEDICARBOXYLATES

Heating N-(benzotriazol-l-yl)glycine ethyl esters 2, obtained by Mannich condensation of glycine ethyl esters 1, formaldehyde and benzotriazole, in THF in the presence of excess of NaH unexpectedly gave diethyl fra/w-2,3-piperazinedicarboxylates 2. Work in our group has demonstrated the versatility of benzotriazole as a synthetic auxiliary in organic synthesis (1-4). The benzotriazole anion is a good leaving group and can be used in place of a halogen or other substituents in many transformations. In particular, we found that the benzotriazole group in Mannich adducts (RlR^NCHRBt), readily prepared from condensation of a secondary amine, an aldehyde and benzotriazole, can be easily displaced by carbanions from RMgBr and RLi or reduced by NaBH4 under mild conditions to give tertiary amines (5-7). These convenient intermolecular substitutions prompted us to investigate the possibility of intramolecular substitution utilizing benzotriazole as a leaving group to synthesize cyclic compounds.

Formation of 1-(2-aminophenyl)-5-ethoxy-4-methyl-3-phenylpyrazole and 4-methyl-3-phenylpyrazolo-[5,1-b]benzimidazole via an unusual enzotriazole ring opening

Successive treatment of N-[(1-ethoxy)alken-2-yl]benzotriazoles VII with butyllithium and trimethylsilyl chloride in TH-Fat — 78°C followed by refluxing in acidic acetone generated ring-opened 1-(2-aminophenyl)-5-ethoxy-4-methyl-3 phenylpyrazole VIII and 4-methyl-3 phenylpyrazolo[5, 1-b]benzimidazole IX.

The synthesis and energetic properties of pyridinium and triazolium N-(nitrobenzoyl)-imides

Syntheses of nitrogen rich, energetic N-(nitro-substituted-benzoylimino)pyridinium and N-(nitro- substituted-benzoylimino)1,2,4-triazolium imides are reported and their energetic properties calculated/determined in terms of heats of formation (HOF), densities, detonation parameters, heats of decomposition and heats of combustion.