N-1-Alkyl-2-oxo-2-aryl amides as novel antagonists of the TRPA1 receptor.

A series of potent antagonists of the ion channel transient receptor potential A1 (TRPA1) was developed by modifying lead structure 16 that was discovered by high-throughput screening. Based on lead compound 16, a SAR was established, showing a narrow region at the nitro-aromatic R(1) moiety and at the warhead, while the R(2) side had a much wider scope including ureas and carbamates. Compound 16 inhibits Ca(2+)-activated TRPA1 currents reversibly in whole cell patch clamp experiments, indicating that under in vivo conditions, it does not react covalently, despite its potentially electrophilic ketone.

Benzyl isothiocyanate, a major component from the roots of Salvadora persica is highly active against Gram-negative bacteria.

Plants produce a number of antimicrobial substances and the roots of the shrub Salvadora persica have been demonstrated to possess antimicrobial activity. Sticks from the roots of S. persica, Miswak sticks, have been used for centuries as a traditional method of cleaning teeth. Diverging reports on the chemical nature and antimicrobial repertoire of the chewing sticks from S. persica led us to explore its antibacterial properties against a panel of pathogenic or commensal bacteria and to identify the antibacterial component/s by methodical chemical characterization. S. persica root essential oil was prepared by steam distillation and solid-phase microextraction was used to sample volatiles released from fresh root. The active compound was identified by gas chromatography-mass spectrometry and antibacterial assays. The antibacterial compound was isolated using medium-pressure liquid chromatography. Transmission electron microscopy was used to visualize the effect on bacterial cells. The main antibacterial component of both S. persica root extracts and volatiles was benzyl isothiocyanate. Root extracts as well as commercial synthetic benzyl isothiocyanate exhibited rapid and strong bactericidal effect against oral pathogens involved in periodontal disease as well as against other Gram-negative bacteria, while Gram-positive bacteria mainly displayed growth inhibition or remained unaffected. The short exposure needed to obtain bactericidal effect implies that the chewing sticks and the essential oil may have a specific role in treatment of periodontal disease in reducing Gram-negative periodontal pathogens. Our results indicate the need for further investigation into the mechanism of the specific killing of Gram-negative bacteria by S. persica root stick extracts and its active component benzyl isothiocyanate.

Syntheses, characterizations, and biological activities of tetradeca-4,8-dien-1-yl acetates as sex attractants of leaf-mining moth of the genus Phyllonorycter (Lepidoptera: Gracillariidae).

The four possible isomers of tetradeca-4,8-dien-1-yl acetate and corresponding alcohols were synthesized stereoselectively by synthetic routes employing Wittig coupling reaction for the preparation of (Z,E)- and (Z,Z)-isomers, and alkylation of terminal alkynes for the preparation of (E,E)- and (E,Z)-isomers as the key steps. Synthetic products were characterized by 13C- and 1H-NMR spectroscopy as well as mass-spectrometric methods. All four isomers gave distinctive mass spectra where m/z 81 fragments clearly dominated. Elution order, followed by retention index presented in parenthesis, of tetradeca-4,8-dien-1-ols was determined as (Z,Z) (2082.1), (Z,E) (2082.8), (E,E) (2083.1), and (E,Z) (2083.2) from unpolar SPB-1 column, and as (E,E) (2210.2), (Z,E) (2222.1), (E,Z) (2223.4), and (Z,Z) (2224.7) from polar DB-WAX column. The isomers of tetradeca-4,8-dien-1-yl acetates eluted in the order of (Z,Z) (2176.1), (Z,E) (2178.4), (E,Z) (2185.9), and (E,E) (2186.4) from SPB-1, and (Z,E) (2124.3), (E,E) (2157.7), (Z,Z) (2128.9), and (E,Z) (2135.9) from DB-WAX columns. Field-screening tests for attractiveness of tetradeca-4,8-dien-1-yl acetates revealed that (4Z,8E)-tetradeca-4,8-dien-1-yl acetate significantly attracted Phyllonorycter coryli and Chrysoesthia drurella males. (4E,8E)-Tetradeca-4,8-dien-1-yl acetate was the most efficient attractant for Ph. esperella and Ph. saportella males, and (4E,8Z)-tetradeca-4,8-dien-1-yl acetate was attractive to Ph. cerasicolella males.

Simplified isolation procedure and interconversion of the diastereomers of nepetalactone and nepetalactol.

Three nepetalactones were isolated from Nepeta racemosa (mussinii) by traditional methods. An improved method was developed to isolate nepetalactones from N. faassénii. An epimerization procedure was used to prepare the fourth 7S-nepetalactone diastereomer. The cis-fused nepetalactols were prepared by reduction of the corresponding nepetalactones, while the trans-fused nepetalactols were unstable and found to undergo ring-opening reactions yielding iridodials. The characterizations and structural assignments by means of NMR agree with quantum chemical density functional calculations.

Electrophysiological studies and identification of possible sex pheromone components of Brazilian populations of the sugarcane borer, Diatraea saccharalis.

Virgin female gland extracts of sugarcane moth Diatraea saccharalis (Fabricius) (Lepidoptera: Pyralidae), from three locations in Brazil, have been analyzed. By GC-MS analysis and comparison of the chromatographic retention time of the components of the pheromone gland with those retention times of synthetic standards, we observed the presence of (Z)-hexadec-11-enal (1), hexadecanal (2), (9E,11Z)-hexadecadienal (4), (9Z,11Z)-hexadecadienal (5) and (9E,11E)-hexadecadienal (6), as minor components besides the major constituent (9Z,11E)-hexadecadienal (3) already reported. We found no variations in the composition of the gland extracts deriving from the three Brazilian populations and only two compounds, (Z)-hexadec-11-enal (1) and (9Z,11E)-hexadecadienal (3), elicited antennal responses (GC-EAD). In electroantennography (EAG), however, pure compounds 1 and 3, a binary mixture containing 1 and 3, and a mixture containing all of the six synthetic compounds 1-6 elicited a depolarization in male antennae of D. saccharalis, without any statistically different delay. The EAG responses to the other isomers of 9,11-hexadecadienal were small and not significantly different from the control, except for the (9Z,11Z)-isomer (5) which showed an relatively strong electroantennal activity.

Identification, syntheses, and characterization of the geometric isomers of 9,11-hexadecadienal from female pheromone glands of the sugar cane borer Diatraea saccharalis.

Chemical analysis of the pheromone glands of the sugar cane borer Diatraea saccharalis has shown the presence of the four geometric isomers of 9,11-hexadecadienal (1-4), in addition to hexadecanal and (Z)-hexadec-11-enal. We here report the syntheses and characterization of compounds 1-4. One starting material, 9-decen-1-ol, has been used to obtain all of them via divergent synthetic routes.