Some Useful Synthetic Applications of Gold\u27s Reagent

While looking for some appropriate research projects, I had been impressed by and interested in the work of Danishefsky1 and others2 regarding the use of Eschenmoser\u27s salt (1). During the course of a literature search on an industrial project, we came across an article by Gold,3 which described the preparation of a rather interesting vinylogous iminium salt (2). The name assigned to this compound was [3-(dimethylamino)-2-azaprop-2-en-1-ylidene]dimethylammonium chloride. This terminology seemed a little cumbersome for routine discussions so we adopted the name Gold\u27s Reagent for compound 2. Although the reagent had been prepared3 in 1960, very little research4 had been performed on this substance in the intervening years. We therefore decided to begin an exhaustive study to delineate and define what, if any, useful synthetic chemistry could be developed from Gold\u27s Reagent

Insecticides Based on Differences in Metabolic Pathways

Insects have been major pests of humankind at least since the beginning of recorded history. To this day insects continue to cause problems in domestic, agricultural, and health situations. It is no wonder that people have continually sought new solutions to controlling insect pests. Even when new control methods are discovered and established, insects evolve into resistant species so that the method is only of real value for a few brief years. Modern science and technology are now enabling scientists to tear away the fabric that has so long masked physiological and biochemical events critical to insects. Armed with this new knowledge, researchers should be able to develop novel control strategies that focus on key physiological, biological, and biochemical events such that they can be altered, influenced, disrupted, and/or inhibited. Three promising areas that may lead or are currently leading to new insect control methods are the cuticle, prostaglandins, and steroids. We discuss each of these areas in regard to their biological significance, current research, metabolic inhibitors and their modes of action

Process for the production of 2-alkyl or 2-cycloalkyl-4-methyl-6-hydroxypyrimidines

Production of 2-alkyl or 2-cycloalkyl-4-methyl-6-hydroxy pyrimidines by sequentially reacting without isolation of any intermediates in an organic solvent (1) diketene and ammonia to produce .beta.-aminocrotonamide and (2) .beta.-aminocrotonamide, after water removal therefrom, a lower alkanoic or cycloalkanoic acid ester and an alkali metal alkoxide

Method for Direct Preparation for 1,2,4-Triazole from Hydrazine and Formamide

Process for the preparation of 1,2,4-triazole comprises contacting hydrazine or its aqueous solutions with at least about 2.5 moles of formamide at a temperature of 140° to 210° C. and then recovering the resultant 1,2,4- triazole in yields of 92-98% with 94-98% purity. The formamide is maintained in an excess over about the 2.5 molar amount consumed in the reaction with the hydrazine. Recovery steps for isolating the 1,2,4-triazole are disclosed

Effects of a Pyrrole-Based, Microtubule-Depolymerizing Compound on RAW 264.7 Macrophages

RAW 264.7 murine macrophages were exposed to the pyrrole-based compound 3,5-Dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester (JG-03-14), which is a known microtubule depolymerizing agent with antitumor activity [1,2,3]. In this study exposure to JG-03-14 reduced the production of pro-inflammatory molecules by macrophages activated with lipopolysaccharide (LPS). Treatment with the pyrrole-based compound decreased the concentration of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) released from the macrophages. Exposure to JG-03-14 also decreased TNF-α mRNA expression levels and the protein expression levels of inducible nitric oxide synthase (iNOS), the enzyme responsible for NO production in the activated macrophages. Furthermore, JG-03-14 treatment significantly changed the degradation profile of IκB-β, an inhibitor of the NF-κB transcription factor, which suggests that JG-03–14 may attenuate the activation of the LPS-induced NF-κB signaling pathway needed to produce the pro-inflammatory mediators. We conclude that JG-03-14 possesses anti-inflammatory properties

Efficient and General Synthesis of Novel β-Polyfluoroalkoxy Vinamidinium Salts

Novel β-polyfluoroalkoxy vinamidinium salts 3 and/or 4 were synthesized in good yields by the reaction of N-(2- polyfluoroalkoxy-3 ,3-difluoro-1-propenyI)trimethylammonium iodides (2), prepared from N-(2,3,3-trifluoro-1-propenyl)trimethylammonium iodide (1), with secondary amines in MeCN at 70 °C for 1 h. The salts were also obtainable in comparable yields by the one-pot reaction of 1 with sodium polyfluoroalkoxide followed by treatment with amines

Photochemical Rearrangements of 6/5 -Fused Cross-conjugated Cyclohexadiensnes in Protic Solvents

Irradiation of the ring A unsubstituted 6/5-fused cross-conjugated cyclohexadienone (1a) and its 2-methyl derivative (1b) in methanolic acetic acid yields, in addition to other products, novel tricyclononane derivatives which have been assigned the structures (3a) and (3b)

Process for the production of 2-alkyl or 2-cycloalkyl-4-methyl-6-hydroxypyrimidines

Production of 2-alkyl or 2-cycloalkyl-4-methyl-6-hydroxy pyrimidines by first reacting diketene and lower alkanoic or cycloalkanoic acid amides in the presence of catalytic amounts of Lewis bases or Lewis or Bronsted acids, followed by treating the N-acetoacetyl (lower) alkanoic or cycloalkanoic acid amide intermediates with ammonia in the presence of acid catalysts

A Process for the Production of 2-Alkyl or 2-Cycloalkyl-4-methyl-6-hydroxypyrimidines

Production of 2-alkyl- or cycloalkyl-4-methyl-6- hydroxypyrimidines by first neutralizing an alkyl imidate ester hydrochloride with a base in the presence of a water-immiscible solvent for the alkyl imidate ester to be freed thereby; condensing the alkyl imidate ester with diketene to form an oxazinone intermediate, which is then reacted in organic solution with gaseous ammonia and recovering the desired substituted 6-hydroxypyrimidine

Identification and Characterization of a New Tubulin-Binding

We studied the mechanism of action of 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester (JG-03-14) and found that it is a potent microtubule depolymerizer. JG-03-14 caused a dose-dependent loss of cellular microtubules, formation of aberrant mitotic spindles, accumulation of cells in the G2/M phase of the cell cycle, and Bcl-2 phosphorylation. These events culminated in the initiation of apoptosis, as evidenced by the caspase 3-dependent cleavage of poly(ADP-ribose) polymerase (PARP). JG-03-14 has antiproliferative activity against a wide range of cancer cell lines, with an average IC50 value of 62 nM, and it is a poor substrate for transport by P-glycoprotein. JG-03-14 inhibited the polymerization of purified tubulin in vitro, consistent with a direct interaction between the compound and tubulin. JG-03-14 potently inhibited the binding of [3H]colchicine to tubulin, suggesting that it bound to tubulin at a site overlapping the colchicine site. JG-03-14 had antitumor effects in the PC3 xenograft model, in which it caused greater than 50% reduction in tumor burden after 14 days of treatment. Molecular modeling studies indicated that the dimethoxyphenyl group of JG-03-14 occupies a space similar to that of the trimethoxyphenyl group of colchicine. However, the 2,3,5-trisubstituted pyrrole group, which is connected to the dimethoxyphenyl moiety, interacted with both α and β tubulin in space not shared with colchicine, suggesting significant differences compared with colchicine in the mechanism of binding to tubulin. Our results suggest that this tetransubstituted pyrrole represents a new, biologically active chemotype for the colchicine site on tubulin