Racemic chiral O,N-heterocycles containing 2-arylchroman or 2-aryl-2H-chromene subunit condensed with morpholine, thiazole, or pyrrole moieties at the C-3-C-4 bond were synthesized with various substitution patterns of the aryl group by the cyclization of cis- or trans-3-aminoflavanone analogues. The 3-aminoflavanone precursors were obtained in a Neber rearrangement of oxime tosylates of flavanones, which provided the trans diastereomer as the major product and enabled the isolation of both the cis- and trans-diastereomers. The cis- and trans-aminoflavanones were utilized to prepare three diastereomers of 5-aryl-chromeno[4,3-b][1,4]oxazines. Antiproliferative activity of the condensed heterocycles and precursors was evaluated against A2780 and WM35 cancer cell lines. For a 3-(N-chloroacetylamino)-flavan-4-ol derivative, showing structural analogy with acyclic acid ceramidase inhibitors, 0.15 μM, 3.50 μM, and 6.06 μM IC50 values were measured against A2780, WM35, and HaCat cell lines, and apoptotic mechanism was confirmed. Low micromolar IC50 values down to 2.14 μM were identified for the thiazole- and pyrrole-condensed 2H-chromene derivatives. Enantiomers of the condensed heterocycles were separated by HPLC using chiral stationary phase, HPLC-ECD spectra were recorded and TDDFT-ECD calculations were performed to determine the absolute configuration and solution conformation. Characteristic ECD transitions of the separated enantiomers were correlated with the absolute configuration and effect of substitution pattern on the HPLC elution order was determined.
The present study has focused on an investigation of the antibacterial effects of Juncus inflexus and the isolation and identification of its active compounds. Eleven phenanthrenes were isolated from a methanolic extract of the roots. Four compounds (jinflexins A–D, 1–4) are new natural products, while seven phenanthrenes [juncuenins A (5), B (6), and D (8), juncusol (7), dehydrojuncuenins A (9) and B (11), and dehydrojuncusol (10)] were isolated for the first time from the plant. Jinflexin D (4) is a dimer with an unprecedented heptacyclic ring system. The absolute configurations of the new compounds were determined by TDDFT-ECD calculations, and their enantiomeric purity was checked by chiral HPLC analysis. Extracts of different polarity (n-hexane, dichloromethane, and ethyl acetate) were evaluated for their antimicrobial effects against methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase (ESBL)-producing Citrobacter freundii, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, multiresistant Acinetobacter baumannii, and Pseudomonas aeruginosa. The MIC values of the isolated compounds were determined by a microdilution method. Jinflexin B (2), juncusol (7), juncuenin D (8), and dehydrojuncuenin B (11) showed significant activity (MIC value range 12.5–100 μg/mL) against MRSA strains.
From an extract of red mamey (Pouteria sapota) β-cryptoxanthin-5,6-epoxide, β-cryptoxanthin-5′,6′-epoxide, 3′-deoxycapsanthin, and cryptocapsin were isolated and characterized by UV–vis spectroscopy, electronic circular dichroism (ECD), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). Epoxidation of β-cryptoxanthin delivered the β-(5′R,6′S)- and (5′S,6′R)-cryptoxanthin-5′,6′-epoxides, which were identified by HPLC-ECD analysis. These carotenoids among others are quite common in the fruits of Central America, and as they are natural provitamins A, they should play an important role in the diet of the mostly vitamin A deficient population of this region.
The fruit of red mamey (Pouteria sapota) contains a wide variety of carotenoids, generally in high concentration, which makes possible even the isolation of minor components in measurable amounts. Carotenoids were extracted from red mamey with acetone, subsequent saponification resulted a crude extract, which was submitted to column chromatography using aluminium oxide (Al2O3) as adsorbent. By using consecutive chromatographic steps and crystallization allene carotenoids, such as neoxanthin, (9'Z)-neoxanthin and capsoneoxanthin, were isolated from the most polar fractions in milligram amounts and in high purity. The amount of capsoneoxanthin was found sufficient for the complete analysis of this rare carotenoid 15 years after its first isolation. The complete 1H- and 13C NMR assignments of neoxanthin and (9'Z)-neoxanthin using 2D techniques were achieved for the first time, as well. Electronic Circular Dichroism (ECD) spectra for the neoxanthin isomers were in good accordance with literature data, whereas the spectrum of capsoneoxanthin suggested aggregate formation in n-hexane solution.
Starting from racemic naringenin ((±)- 1 ), a mixture of dracocephin A stereoisomers 6-(2”-pyrrolidinone-5”-yl)naringenin (±)- 2a–d and its regioisomer, dracocephin B 8-(2”-pyrrolidinone-5”-yl)naringenin (±)- 3a–d originally isolated from Dracocephalum rupestre , have been synthesized in a one-pot reaction. The separation of 2a–d and 3a–d was achieved by preparative HPLC. The four stereoisomers of each natural product were separated by analytical chiral HPLC and their absolute configuration was studied by the combination of HPLC–ECD measurements and TDDFT–ECD calculations. The synthesized flavonoid alkaloids were further characterized by physicochemical and in vitro pharmacological studies.
The Heck-oxyarylation of racemic 2-(1-naphthyl)- and 2-(2-naphthyl)-2H-chromene derivatives were carried out resulting diastereoselectively in (6S*,6aR*,11aR*)-6-(1-naphthyl)- and 6-(2-naphthyl)-pterocarpans as major products and bridged (6R*,12R*)-6,12-methanodibenzo[d,g][1,3]dioxocine derivatives as minor products. Antiproliferative activity of two 6-naphthylpterocarpans was identified by MTT assay against A2780 and WM35 human cancer cell lines with low micromolar IC50 values. The measured 0.80 and 3.51 μM IC50 values of the (6S*,6aR*,11aR*)-6-(1-naphthyl)pterocarpan derivative with 8,9-methylenedioxy substitution represent the best activities in the pterocarpan family. Enantiomers of the pterocarpan and dioxocine derivatives and their chiral 2-naphthylchroman-4-one and 2-naphthyl-2H-chromene precursors were separated by HPLC using chiral stationary phase. HPLC-ECD spectra were recorded and absolute configuration and low-energy solution conformations were determined by TDDFT-ECD calculations. Characteristic ECD transitions of the separated enantiomers were correlated with their absolute configuration.
The Heck-oxyarylation of racemic 2-phenyl-2H-chromene [(±)-4b] and 1,2-dihydronaphthalenes (14a,b) has been studied with 2-chloromercuriphenols (5a-d) in the presence of Li 2 [PdCl 4 ] catalyst.The reactions resulted in the diastereoselective formation of racemic 6phenylpterocarpans of (6R, 6aR,11aR) relative configuration [(±)-8a-d] and their dibenzo[1,3]dioxocine analogues [(±)-12a-d] as main products, respectively.The ratio of products and the lack of regioisomeric products (13a-d) corroborated the cationic mechanism of the oxyarylation of 2H-chromenes, which has been also supported by the transformation of 14a,b under similar conditions.(
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