The reaction of β-aminoenones with substituted acetonitriles. Regiospecific synthesis of 2(1H)-pyridones

Unsymmetrically substituted β-aminoenones react with malononitrile, cyanomethylphenylsulfone, benzoyl-acetonitrile and ethyl cyanoacetate, in very mild conditions, to yield regiospecifically 3-functionalized 2(1H)-pyridones in high yields.     

Enantioselective radical cyclisation reactions of 4-substituted quinolones mediated by a chiral template

Six 4-substituted quinolones 6-8, which bear an ω-iodoalkyl chain, were prepared and subjected to reductive radical cyclisation conditions employing BEt(3)/O(2) as the initiator and either Bu(3)SnH or TMS(3)SiH as hydride source. 4-(4-Iodobutyl)-quinolone (6a) and 4-(3-iodopropylthio)-quinolone (8a) gave the respective 6-endo-cyclisation products in good yields. 4-(3,3-Dimethyl-4-iodobutyl)-quinolone (6b) cyclised in a 5-exo-fashion, while the other substrates delivered only reduction products. The cyclisation reactions could be conducted in the presence of a chiral template (1) with high enantiomeric excess (94-99% ee). The association behaviour of substrate 6a to 1 was studied by NMR titration experiments. In the enantioselective cyclisation of 6b a significant nonlinearity was observed when comparing the product ee with the ee of the template.     

Use of 9-methylfluorene as an indicator in the titration of common group IA and group IIA organometallic reagents

9-Methylfluorene was tested as an indicator in the titration of commonly used organometallic reagents. This indicator is readily prepared in three steps from fluorenone. In THF solution the deprotonated indicator is red and exhibits a sharp endpoint. The highly basic reagents sec-butyllithium and tert-butyllithium can be titrated in ether solution, where the color of the deprotonated indicator is yellow.     

Antioxidant activity,lipophilicity and extractability of polyphenols from pig skin – development of analytical methods for skin permeation studies

Permeation of polyphenols through the stratum corneum barrier is a precondition for the protective action of polyphenols against oxidative skin damage. Prior to in vitro skin permeation experiments, we developed a method for the quantification of polyphenols in pig skin, including organic solvent extraction and HPLC analysis. Catechine hydrate, epigallocatechin gallate, trans‐resveratrol, quercetin, rutin and protocatechuic acid were chosen for this study as representatives of phenolics with different lipophilicity and molecular weight. The antioxidative activities of polyphenols as well as their octanol–water partition coefficients at different pH values were determined. Extraction of polyphenols from pig skin was optimized by variation of solvent composition, homogenization intensity and time, as well as partial exclusion of oxygen during extraction. The highest recovery rates could be reached by extraction with the methanol–water mixture (90:10, v/v), containing 0.2 g/L l ‐ascorbic acid, after the cryo‐milling for 4 min. Recoveries of 72% for total phenolics, 96% for quercetin and protocatechuic acid, 90% for rutin and 74% for trans‐resveratrol, were achieved. These extraction parameters will be selected for the polyphenol extraction from pig skin for further in vitro drug permeation studies. Copyright © 2013 John Wiley & Sons, Ltd.     

Reexamination of CeCl3 and InCl3 as activators in the diastereoselective Mukaiyama aldol reaction in aqueous media

A search for suitable reaction conditions in Mukaiyama-type aldol condensations activated by CeCl(3) and InCl(3) revealed that the reaction proceeds best in i-PrOH/H(2)O (95:5). Contrary to literature precedent, no reaction was observed in pure water, and the encountered destruction of the starting silyl enol ether can be ascribed to initial hydrolysis of the Lewis acid. As anticipated from the dual parameter (pK(h), WERC value) characteristics of CeCl(3) and InCl(3), the former proved more efficient as Lewis acid-promoter, in terms of reaction speed and yield. Nevertheless, InCl(3) was a superior catalyst during evaluation of the diastereoselectivity of the process. In this regard, determination of diastereoselectivity as a function of time showed that the InCl(3)-catalyzed reaction is irreversible, whereas the CeCl(3)-catalyzed reaction is a reversible process. In both cases, formation of the syn product is kinetically preferred, although DeltaDeltaG(++)273K(InCl(3)) = 1.50 kcal/mol versus DeltaDeltaG(++)273K (CeCl(3)) = 0.38 kcal/mol. Molecular modeling (semiempirical PM3, ab initio HF/3-21G*, hybrid B3LYP/3-21G*, and B3LYP/LANL2DZ) of the diastereoselective aldol reaction promoted by InCl(3) supports a "closed", Zimmermann-Traxler transition state.