Synthesis of some 1-substituted-3-or-5-styrylpyrazoles

The synthesis of the title compounds by the Wittig-Horner reaction is described, using the 3-or-5-hydroxymethylpyrazole derivatives as precursors.     

Synthèse de 2H -furo[3,4-b] (3H, 5H, 7H) pyrannediones-4,5. Acylation de (2H, 5H) furannediones-2,4 (acides tétroniques) par les chlorures d'acides α-éthyléniques

Direct acylation of tetronic acids by α,β-ethylenic acid chlorides with tin tetrachloride gave a new type of fused heterocyclic compounds: 2H-furo[3,4-b] pyran-4,5-diones. Acylation in alkaline medium gave enol esters which could be transposed in furopyrandiones. However, the first route was more satisfactory.     

An entry into the novel tetracyclic system 6H-pyrido[1′,2′:4,5]pyrazino[1,2-a]benzimidazole. Synthesis and conformational study of the 1,2,3,4,13,13a-hexahydro-3,3-ethylenedioxy and 3-ketone derivatives

The synthesis of the tetracyclic title compounds, acetal 5 and ketone 6 , is presented. The key step, formation of the imidazole ring to give compound 5 , involved the acid catalysed dehydration of the 2-(o-aminophenyl)lactam 7b . This was generated from lactam 4 via N-substitution with o-nitrofluorobenzene and reduction of the nitro group. Deprotection of acetal 5 afforded ketone 6 which through a temperature dependence study of vicinal coupling constants was shown to occur as an equilibrium of trans- and cis-fused forms A and B .     

Configurations and conformations of some 3-acetoxy-cis-hexahydro-2(3H)-benzofuranones

Catalytic hydrogenation of some 2-ethoxalylcyclohexanones afforded a mixture of isomeric 3-hydroxy-cis-hexahydro-2(3H)-benzofuranones. Three 5-t-butyl substituted diastereomers and two 5-unsubstituted epimers were separated and identified as acetates. The configurations were determined by 350 MHz ¹H-nmr analysis. The conformations of these fused-compounds are discussed.     

Photochemical sources of organic acids. 1. Reaction of ozone with isoprene, propene, and 2-butenes under dry and humid conditions using SPME

Formation of C4 and smaller carboxylic acids from gas-phase ozonolysis of several alkenes under dry (relative humidity (RH) < 1%) and humid (RH = 65%) conditions have been investigated. We have developed a technique based on solid-phase microextraction (SPME) and gas chromatography/mass spectrometry (GC/MS) to quantify the acids, as well as other products, and applied it to the reactions of ozone with propene, trans-2-butene, 2,3-dimethyl-2-butene, and isoprene. Acetic acid yields from propene and trans-2-butene ozonolysis in the presence of an OH scavenger were 2.7 +/- 0.6 and 2.9 +/- 0.6%, respectively, under dry conditions and 1.8 +/- 0.4 and 2.3 +/- 0.5% at 65% RH. Isoprene ozonolysis produced methacrylic and propenoic acids with yields of 5.5 +/- 1 and 3.0 +/- 1%, under dry conditions and 4.1 +/- 1 and 1.5 +/- 0.3% under wet conditions, respectively. That water inhibits acid formation indicates that the water reaction with stabilized Criegee intermediates is at most a minor source of acids. Acids that may form as coproducts of the OH radical elimination pathway, acetic acid from 2,3-dimethylbutene and isoprene, and propenoic acid from isoprene were also observed with significant yields (up to 10%), although the production of acetic acid was not a linear function of the alkene reacted. Carbonyl products are also reported.     

Determination of inorganic phosphate in serum and saliva using a synthetic receptor

[structure: see text] A C(3)(v) symmetric synthetic receptor (1) was employed in an indicator-displacement assay to determine the phosphate concentrations in both horse serum and human saliva at biological pH. The determination of the phosphate concentrations in the serum and saliva using the colorimetric assay were 1.6 and 5.1 mM, respectively. These results further accentuate the usefulness of synthetic receptors in truly practical applications.     

Data shaving: a focused screening approach

The number of compounds available for evaluation as part of the drug discovery process continues to increase. These compounds may exist physically or be stored electronically allowing screening by either actual or virtual means. This growing number of compounds has generated an increasing need for effective strategies to direct screening efforts. Initial efforts toward this goal led to the development of methods to select diverse sets of compounds for screening, methods to cluster actives into related groups of compounds, and tools to select compounds similar to actives of interest for further screening. In this work we extend these earlier efforts to exploit information about inactive compounds to help make rational decisions about which sets of compounds to include as part of a continuing screening campaign, or as part of a focused follow-up effort. This method uses the information from inactive compounds to "shave" off or deprioritize compounds similar to inactives from further consideration. This methodology can be used in two ways: first, to provide a rational means of deciding when sufficient compounds containing certain structural features have been tested and second as a tool to enhance similarity searching around known actives. Similarity searching is improved by deprioritizing compounds predicted to be inactive, due to the presence of structural features associated with inactivity.     

Rapid extraction of abscisic acid and its metabolites for liquid chromatography-tandem mass spectrometry

We have described a simple, reliable and rapid method of extracting and partially purifying the phytohormone (+)-abscisic acid and its catabolites for liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) analysis. Lyophilized tissue samples were powdered by high-speed agitation with ceramic beads for 5 s. Metabolites were extracted from the tissue powder using acetone-water-acetic acid (80:19:1, v/v) with the addition of deuterated internal standards for quantification. Essentially all endogenous hormones were recovered by three successive tissue extractions. However we demonstrated that, with the use of internal standards, one extraction with vigorous vortexing was sufficient to obtain accurate results (recovery 65-90%). Solvents were optimized for partial purification of abscisic acid and related compounds by solid-phase extraction using Oasis HLB cartridges. The eluted metabolites were then analyzed by LC-MS-MS. To illustrate the applicability of these techniques, we analyzed the levels of abscisic acid and metabolites in seeds and valves of Brassica napus siliques at two stages of development. We detected abscisic acid, phaseic acid, 7'-hydroxyabscisic acid, dihydrophaseic acid and abscisic acid glucose ester. In both tissues, dihydrophaseic acid was the major accumulating product, reaching 97300 pmol/g dry mass in valves at 24 days after anthesis. The amount of abscisic acid in seeds was high at 24 days after anthesis (23300 pmol/g dry mass), but low in the other samples (292-447 pmol/g dry mass).     

5-Imino-Δ3-1,2,4-thiadiazoline derivatives with a linear N-S…O grouping. Synthesis and crystal structures

A series of carbonyl derivatives of 5-imino-Δ³-1,2,4-thiadiazolines has been prepared and shown by X-ray analysis of a selected example to have a trithiapentalene-like structure. When diphenylketene was used as acylating reagent, the primary product ( 14 ), obtained at room temperature, rearranged on heating in a polar solvent into a Δ²-thiazolin-4-one ( 15 ). The structure of 15 has been confirmed by X-ray analysis, and shown to be a zwitterion. Rearranged products (i.e., 16 and 20-22 ) were also obtained when 3 was reacted with dimethyl acetylenedicarboxylate or methanesulfonyl chloride, whereas tosyl chloride gave normal tosylated derivatives ( 17-19 ). The latter have also a nearly linear N-S…O arrangement, but the interaction between S and O is weak.