[reaction: see text] The catalytic activity of the prolinamide-type catalysts may be improved by introducing additional prolinamide moiety into the catalyst, while the enantioselectivity can still be maintained or further improved. A C2-symmetric bisprolinamide with two prolinamide moieties has been found to be an excellent catalyst for direct aldol reaction with more than doubled reactivity and better asymmetric induction than its monoprolinamide counterpart.

A new indolo[3,2-b]quinoline alkaloid glycoside, jusbetonin (1), and three known alkaloids, namely, 10H-quindoline (2), 6H-quinindoline (3), and 5H,6H-quinindolin-11-one (4), have been isolated from the leaves of Justicia betonica. The structure of 1 was established on the basis of 1D and 2D NMR ((1)H-(1)H COSY, HMQC, and HMBC) and HRFABMS data. Compound 1 is the first example of a glycosylated indolo[3,2-b]quinoline alkaloid, while compound 4 was isolated for the first time from a natural source.

Streptomyces padanus strain PMS-702 is an antagonist of Rhizoctonia solani AG-4, the causal agent of damping-off of cabbage. Treatment of cabbage seeds with the culture filtrate of S. padanus strain PMS-702 was effective in reducing the incidence of damping-off of cabbage. The major active ingredient from the culture filtrate of S. padanus strain PMS-702 was purified by silica gel column chromatography and identified as the polyene macrolide, fungichromin, by NMR and mass spectral data. Bioassay studies showed that fungichromin had a strong antifungal activity against R. solani AG-4, and its minimum inhibitory concentration (over 90% inhibition) was found to be 72 microg/mL. This is the first report of fungichromin from S. padanus as an active ingredient for the control of Rhizoctonia damping-off of cabbage.

Enantioenriched 2,3,4-trisubstituted thiochromanes have been synthesized by using a cupreinecatalyzed tandem Michael addition-Henry reaction between 2-mercaptobenzaldehydes and β-nitrostyrenes. Good diastereoselectivities and enantioselectivities were obtained for the title compounds, which may be further improved through a single recrystallization (up to 98% de and> 99% ee). KeywordsHenry reaction; 2-mercaptobenzaldehyde; Michael addition; β-nitrostyrene; organocatalysis; tandem reaction Chromanes are an important class of compounds that are found in many biologically active natural products.[1] Thiochromanes, the sulfur analogues of chromanes, have also been reported to possess important biological activities. [2] There are also reports that the replacement of the oxygen atom in chromanes with a sulfur atom results in enhanced bioactivities.[2d,f] Some representative examples are collected in Figure 1. Tertatolol (1) has been shown to have affinity to 5HT A1 receptors in human and rat brains. [2a,b] Thiochromane derivative 2 also displays a mixed binding affinity to dopamine D 2 , D 3 and 5HT A1 receptors, [2d] whereas thiochromane derivative 3 shows potent anti-HIV activity. [2e] Owing to their biological activities, several asymmetric methods have been developed for the synthesis of these compounds, which include asymmetric reduction of thiochroman-4-ones, [3] enzymatic resolution of racemic 4-hydroxythiochromanes or 4-acyloxythiochromanes, [4] and enantioselective alkylation of thiochromanes via conjugate addition.[5] Last year Wang and co-workers reported an enantioselective tandem Michael-aldol reaction for the synthesis of thiochromenes catalyzed by a proline derivative.[6] Most recently, the same group also reported a quinine thiourea-catalyzed tandem Michael-aldol reaction for synthesis of [13] Moreover, the synthesis of thiochromanes by using this tandem reaction has never been studied.[14] Herein, we report an organocatalytic, enantioselective tandem Michael-Henry reaction for the direct synthesis of 2-aryl-3-nitro-4-hydroxythiochromanes.By using 2-mercaptobenzaldehyde (8) and β-nitrostyrene (9) as the model compounds, we initially studied the tandem Michael-Henry reaction using 5 mol% of DABCO as the catalyst at room temperature (entry 1, Table 1). We were pleased to find that the reaction was completed in just 5 min and only two diastereomers of the expected 2-phenyl-3-nitro-4-hydroxythiochromane (10a) were obtained in a ratio of 70:30, according to the 1 H NMR analysis of the crude product. Encouraged by this result, we further screened some readily available alkaloid catalysts 4-7 (Figure 2) in an effort to develop an enantioselective reaction, and the results are summarized in Table 1.As shown in Table 1, with 5 mol% loading of quinine (4) in diethyl ether, the reaction of 8 and 9 proceeds smoothly, and complete conversion was achieved in just 5 min (entry 2). The same two diastereomers were formed in a ratio of 75:25. However, the ee value of the major diastereomer was only 8% fo...

[reaction: see text] The first organocatalytic cross aldol reaction of ketones and diethyl formylphosphonate hydrate has been realized by using readily available l-prolinamide as the catalyst. Secondary alpha-hydroxyphosphonates have been synthesized in high enantioselective (up to >99% ee) and good diastereoselectivity.

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A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and fully validated for simultaneous quantification of donepezil and its active metabolite, 6-o-desmethyl donepezil in human plasma. Analytes and the internal standard were extracted from human plasma by liquid-liquid extraction technique using a 30:70 v/v mixture of ethyl acetate and n-hexane. The reconstituted samples were chromatographed on a C(18) column by using a 70:30 v/v mixture of acetonitrile and ammonium formate (5 mm, pH 5.0) as the mobile phase at a flow rate of 0.6 mL/min. The calibration curve obtained was linear (r ≥ 0.99) over the concentration range of 0.09-24.2 ng/mL for donepezil and 0.03-8.13 ng/mL for 6-o-desmethyl donepezil. The results of the intra-day and inter-day precision and accuracy studies were well within the acceptable limits. The proposed method was successfully applied for the estimation of the drug in real time plasma samples for pharmacokinetic studies.

An LC-MS/MS method for the simultaneous quantitation of niacin (NA) and its metabolites, i.e. nicotinamide (NAM), nicotinuric acid (NUA) and N-methyl-2-pyridone-5-carboxamide (2-Pyr), in human plasma (1 mL) was developed and validated using nevirapine as an internal standard (IS). Extraction of the NA and its metabolites along with the IS from human plasma was accomplished using a simple liquid-liquid extraction. The chromatographic separation of NA, NAM, NUA, 2-Pyr and IS was achieved on a Hypersil-BDS column (150 x 4.6 mm, 5 microm) column using a mobile phase consisting of 0.1% formic acid : acetonitrile (20:80 v/v) at a flow rate of 1 mL/min. The total run time of analysis was 2 min and elution of NA, NAM, NUA, 2-Pyr and IS occurred at 1.37, 1.46, 1.40, 1.06 and 1.27 min, respectively. A detailed validation of the method was performed as per the FDA guidelines and the standard curves were found to be linear in the range of 100-20000 ng/mL for NA; 10-1600 ng/mL for NUA and NAM and 50-5000 ng/mL for 2-Pyr with mean correlation coefficient of ≥ 0.99 for each analyte. The method was sensitive, specific, precise, accurate and suitable for bioequivalence and pharmacokinetic studies. The developed assay method was successfully applied to a pharmacokinetic study in humans.