Power Law Distribution Concerning Absolute Free Energies of Linear Sulfur Chains, Polythiazyls, Polyisoprenes, Linear trans-Polyenes, and Polyynes.

After quantum calculations of absolute free energies of polyatomic sulfur derivatives or hydrocarbon oligomer compounds, we have studied the variations of G n as a function of the number of repeating units n (sulfur atoms or hydrocarbon units, n = 2 to about 60), and observed that these values can be correlated by (a) a nearly perfect linear relationship, G n = An + B (A and B, constants), with a high accuracy which enables an extrapolation for higher values of n, and (b) a power law:, δ G = G n/ n - G( n-1) /( n - 1) = C/ n d ( C and d, constants). From comparison of variations of the C-C bond lengths, we show that the conjugation of trans-polyenes (up to C60H62) is more important than for polyynes (up to C60H2).

The ß-phosphorus hyperfine coupling constant in nitroxide: part 3: titration of water by electron paramagnetic resonance.

Recently, we showed that the phosphorus hyperfine coupling constant aPß of persistent cyclic nitroxides decreased with the normalized polarity Reichardt's constant E. Thus, we investigated the changes in aPß in binary mixtures of solvents. The sensitivity of aPß to the solvent was high enough to allow us to perform water titration in THF, 1,4-dioxane, and acetonitrile by EPR. Accuracies of a few percent were achieved.

Efficient synthesis of 17-acetyl-13-(p-bromophenyl)-3-methoxy-11,11-bis(methoxycarbonyl)gona-1,3,5(10)-trienes.

We described an efficient synthesis of (8ß,9ß,14ß)-17ß-acetyl-13ß-p-bromophenyl-11,11-di(methoxycarbonyl)-3-methoxygona-1,3,5(10)-triene, (8ß,9α,14ß)-17ß-acetyl-13ß-p-bromophenyl-11,11-di(methoxycarbonyl)-3-methoxygona-1,3,5(10)-triene, (8ß,9ß,14ß)-13 ß-p-bromophenyl-11,11-di(methoxycarbonyl)-17ß-(2-hydroxyethyl)-3-methoxygona-1,3,5(10)-triene, and (8ß,9ß,14ß)-13ß-p-bromophenyl-11,11-di(methoxycarbonyl)-17ß-(2-oxoxyethyl)-3-methoxygona-1,3,5(10)-triene in five or six steps from 1-iodo-4-methoxybenzocyclobutene and readily available materials.

Palladium-catalysed direct 3- or 4-arylation of 2,5-disubstituted pyrrole derivatives: an economically and environmentally attractive procedure.

Straight to the point: The direct 3- or 4-arylation of pyrrole derivatives through C--H bond activation proceeds in moderate to good yields using Pd(OAc)(2) as catalyst. In contrast to classical coupling procedures, the preparation of an organometallic derivative is not required and the major by-products are AcOH/KBr instead of metallic salts.

Conjugate hydrocyanation of 17-acetyl-11-carbomethoxygona-1,3,5(10),13(17)-tetraenes.

The conjugate hydrocyanation of 17-acetylgona-11-carbomethoxy-1,3,5(10),13(17)-tetraenes using diethylaluminum cyanide (Nagata reaction) is reported. This methodology has allowed the introduction of an angular cyano group at the C-13 position of the steroid skeleton. Subsequent reduction of the nitrile group yielded various functionalized steroids. One of them, 22 bears the natural trans/anti/trans stereochemistry and possesses an hydroxyl and aminomethyl functionalities in the positions 11beta and 13beta, respectively. The characteristic (1)H and (13)C NMR spectroscopic features of the synthesized steroids are reported.

Recent advances in thiasteroids chemistry.

Since it has been proven these last years that the introduction of a heteroatom in the steroidal moiety could have a biological impact, there has been progress in the field of thiasteroids. The recent development in the partial and total syntheses of thiasteroids are herein described.

First total synthesis of (+/-)-3-aza-11-oxa-1,3,5(10)-trieno steroids.

We set out to describe a new and versatile method for preparing 3-aza-11-oxa-1,3,5(10)-trieno steroids via an intramolecular Diels-Alder cycloaddition of o-quinodimethanes as the key step. The characteristic 1H and 13C NMR spectroscopic features of the synthesized compounds are reported.

Agonist specific L-type Ca(2+)-current stimulation in ventricular myocytes by a novel steroid-like compound.

In cardiac muscle the amplitude of Ca(2+) transients can be increased by enhancing Ca(2+) influx. Among the processes leading to increased Ca(2+) influx, agonists of the L-type Ca(2+)-channel can play an important role. Known pharmacological Ca(2+)-channel agonists act on different binding sites on the channel protein, which may lead not only to enhanced peak currents, but also to distinct changes in other biophysical characteristics of the current. In this study, membrane currents were recorded with the patch-clamp technique in the whole-cell configuration in guinea pig isolated ventricular myocytes in combination with confocal fluorescence Ca(2+) imaging techniques and a variety of pharmacological tools. Testing a new positive inotropic steroid-like compound, we found that it increased the L-type Ca(2+)-current by 2.5-fold by shifting the voltage-dependence of activation by 20.2 mV towards negative potentials. The dose-response relationship revealed two vastly different affinities (EC(50(high-affinity))=4.5+/-1.7 nM, EC(50(low-affinity))=8.0+/-1.1 microM) exhibiting differential pharmacological interactions with three classes of Ca(2+)-current antagonists, suggesting more than one binding site on the channel protein. Therefore, we identified and characterized a novel positive inotropic compound (F90927) as a member of a new class of Ca(2+)-channel agonists exhibiting unique features, which set it apart from other presently known L-type Ca(2+)-channel agonists.

Efficient synthesis of C-11 functionalized steroids.

An efficient synthesis from readily available materials of numerous steroids functionalized at C-11 position, interesting from a biological point of view, is described using our general approach. The characteristic (1)H and (13)C NMR spectroscopic features of the synthesized steroids are reported.

A novel steroid-like compound F90927 exerting positive-inotropic effects in cardiac muscle.

Here we report a novel steroid-like compound F90363, exhibiting positive inotropy in vivo and in vitro in various cardiac muscle preparations. F90363 is a racemic mixture composed of the stereoisomers (-)-F90926 and (+)-F90927. Only F90927 exerted positive inotropy, while F90926 induced a weak negative inotropy, but only at concentrations 10(3) times higher than F90927 and most likely resulting from an unspecific interaction. The rapid time course of the action of F90927 suggested a direct interaction with a cellular target rather than a genomic alteration. We could identify the L-type Ca2+ current I(Ca(L)) as a main target of F90927, while excluding other components of cardiac Ca2+ signalling as potential contributors. In addition, several other signaling pathways known to lead to positive inotropy (e.g. alpha- and beta-adrenergic stimulation, cAMP pathways) could be excluded as targets of F90927. However, vessel contraction and stiffening of the cardiac muscle at high doses (>30 microM, 0.36 mg kg(-1), respectively) prevent the use of F90927 as a candidate for drug development. Since the compound may still find valuable applications in research, the aim of the present study was to identify the cellular target and the mechanism of inotropy of F90927.

Catalytic efficiency of a new tridentate ferrocenyl phosphine auxiliary: Sonogashira cross-coupling reactions of alkynes with aryl bromides and chlorides at low catalyst loadings of 10(-1) to 10(-4) mol %.

[structure: see text] The catalytic activity in Sonogashira cross-coupling reactions of alkynes with a variety of aryl halides (including chlorides) using a multidentate ferrocenyl phosphine is presented. The novel mixed ferrocenyl aryl/alkyl triphosphine is thermally stable and insensitive to air or moisture, and its robustness allows aryl alkynylation at 10(-1) to 10(-4) mol % catalyst loadings with TONs up to 250,000. Copper-free coupling using phenylacetylene is also accessible in good yield.

Palladium-tetraphosphine complex: an efficient catalyst for the coupling of aryl halides with alkynes.

The cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)-cyclopentane-[PdCl(eta3-C3H5)]2 system catalyses the coupling of aryl halides with alkynes with very high ratios of substrates-catalyst in good yields; a turnover number of 2600000 can be obtained for the reaction of 4-trifluoromethylbromobenzene with phenylacetylene in the presence of this catalyst.

Cyclododecatetraene tetraepoxide: highly diastereofacial epoxidation of all-(Z)-1,4,7,10-cyclododecatetraene and selective synthesis of bridged bis-oxocanes.

Epoxidation of all-(Z)-1,4,7,10-cyclododecatetraene has been investigated with use of m-CPBA and dimethyldioxirane in anhydrous solvent. The diastereoselectivity of multiple epoxidation steps is complete affording only exo,exo,exo,endo-1,4,7,10-tetraepoxide. To understand this result, the step-by-step epoxidation reaction was investigated and each step was found to be highly regio- and stereoselective. Finally, a Lewis acid-catalyzed ethanolysis or treatment with HBr/KBr of the tetraepoxide gave rearranged diepoxy-oxabicyclo[5.5.1]tridecane (bridged bis-oxocanes) in which eight stereocenters were controlled.

Transmetallation of beta-allenyl silanes: efficient synthesis of dienyl chlorostannanes and chlorostibines.

The reaction of 1-trimethylsilylbuta-2,3-diene with tin tetrachloride, antimony trichloride or antimony pentachloride gave the corresponding buta-1,3-dien-2-yl halostannane or stibine derivatives; this ligand exchange was extended to other beta-allenylsilanes.

pH-dependent interaction of fumonisin B1 with cholesterol: physicochemical and molecular modeling studies at the air-water interface.

Langmuir film balance technology was used to study the interaction between the mycotoxin fumonisin B1 (FB1) and cholesterol. FB1 was added in the aqueous subphase underneath a monomolecular film of cholesterol, and the interaction was measured as an increase in the surface pressure of the film. Above pH 9, a strong inhibition of the reaction was observed. Similar results were obtained with the bile salt sodium taurocholate. The FB1-cholesterol complex was reinforced by NaCl but was destabilized by NaF, a salt known to break hydrogen bonds. These data suggest that the molecular association between FB1 and cholesterol involves both hydrophobic interactions and a hydrogen bond between the NH3(+) group of FB1 and the OH group of cholesterol. Molecular mechanics simulations of the FB1-cholesterol complex were consistent with this hypothesis. These data may shed some light on the mechanisms involved in the intestinal absorption of FB1 and its biliary excretion.

Preparation of delta-Chloro-alpha-allenyl Ketones by Acylation of 3-Buten-1-ynes.

AlCl(3)-mediated acylation of 3-buten-1-yne derivatives with acyl chlorides yields a mixture of 5-chloro-2,3-pentadienones and 3-chloro-2,4-pentadienones. The proportion of allenyl ketones vs conjugated dienic ketones depends on the substitution pattern of the starting enyne. Acylation of 5-acetoxy-3-buten-1-ynes leads to the corresponding allenyl ketones (6-acetoxy-5-chloro-2,3-pentadienones).