Absolute Configurations Of Enantiomers Research Articles

Two sydowic acid derivatives and a sulfonyl metabolite from the endophytic fungus Aspergillus sydowii

Two new sydowic acid derivatives, a pair of enantiomers, involving (+)-sydowiccal (1a) and (−)-sydowiccal (1b), a new sulfonyl metabolite of 2-methoxy-5-methyl-3-(methylsulfonyl)phenol (2), as well as three known sydowic acid derivatives, were isolated from Aspergillus sydowii, an endophytic fungus of Rhododendron mole. The structures of these new compounds were elucidated by analyzing their NMR and HRESIMS data, and the absolute configurations of enantiomers were determined on the basis of the CD spectrum. Three new metabolites showed weak anti-inflammation on nitric oxide (NO) production in LPS-induced RAW 264.7 cells.

Inherently chiral helicene-substituted thioalkyl porphyrazine complexes: synthesis and electronic and chiroptical properties.

The chiral Ni(II) and Pd(II) complexes of [6]helicene thioethyl porphyrazine have been synthesized and their spectroscopic, electrochemical, and chiroptical properties have been investigated by experimental and computational analyses. In these compounds, the tetrapyrrole macrocycle is β-substituted with an inherently chiral extended aromatic moiety potentially suitable to establish attractive π-π interactions with nanocarbons and endowed with helical chirality, both features providing interesting properties for optoelectronic applications. Experimental and density functional theory computational analyses highlight the presence of HOMO-LUMO charge-transfer transitions between the helicene moiety and the porphyrazine macrocycle. These compounds behave as mono-substituted push-pull systems without any typical electron-withdrawing or electron-donating groups and thus appear promising for optoelectronics. The enantiomers of the Ni(II) complex have been separated by chiral HPLC and their absolute configuration has been established by density functional theory computational analysis of electronic circular dichroism spectra. The magnetic circular dichroism spectrum of this complex has also been recorded providing better insight into its electronic structure.

Enantiomeric 8-O-4′-type neolignans from Crataegus pinnatifida exhibit cytotoxic effect via apoptosis and autophagy in Hep3B cells

Crataegus pinnatifida has been famous for its nutritional purpose. However, systematic investigation on the bioactive constituents is still lacking, although this fruit has been reported for its cytotoxic effect before. In this study, two pairs of new lignan enantiomers (1a/1b, 2a/2b), which isolated using chiral chromatographic column from the fruits of C. pinnatifida were studied. The absolute configurations of enantiomers were determined by comparison between the experimental electronic circular dichroism (ECD) and calculated ECD spectra. Among them, 1a/1b exhibited a better cytotoxic effect in hepatocellular carcinoma Hep3B cells with an IC50 value of 34.97 ± 2.74 and 17.42 ± 0.71 μM, respectively. In addition, 1b induced much more apoptotic, autophagic cells than 1a in Hep3B cells. Furthermore, the underlying mechanism was demonstrated that p38 activation could promote 1b-induced apoptosis and autophagy. Moreover, 1b-induced apoptosis was significantly decreased in the presence of autophagic inhibitor Bafilomycin A1 (Baf A1), suggesting that the induction of autophagy enhanced apoptotic cell death in 1b-treated cells. In general, these findings provide a valuable basis for further understanding the effect of 8-O-4′ lignans in C. pinnatifida on cytotoxic effect.

Three new polyketides produced by Penicillium crustosum, a mycoparasitic fungus from Ophiocordyceps sinensis

A pair of novel benzannulated enantiomers, penilactone C [(+)-1 and (-)-1], a known related analogue 6-acetyl-2α,5-dihydroxy-2-(2-hydroxypropyl)-3α,8-dimethylchroman (3), and a novel polyketide, penilactone D (2), were obtained from the liquid-state and solid-state fermentation broth of Penicillium crustosum, a mycoparasitic fungus isolated from the fruiting body of Ophiocordyceps sinensis. The structures of these compounds were elucidated on the basis of spectroscopic data (HRESIMS, NMR and X-ray crystallography). The absolute configurations of enantiomers (+)-1 and (-)-1 were confirmed by TDDFT ECD calculation, and those of compound 2 were determined using Mo2-induced CD analysis. A plausible biogenetic pathway for 1 is proposed.

The determination of enantiomer composition of 1-((3-chlorophenyl)-(phenyl)methyl) amine and 1-((3-chlorophenyl)(phenyl)-methyl) urea (Galodif) by NMR spectroscopy, chiral HPLC, and polarimetry.

For the first time, a method for enantiomer resolution of the anticonvulsant Galodif (1-((3-chlorophenyl)(phenyl)methyl) urea) by chiral HPLC was developed, whereas the enantiomeric composition of 1-((3-chlorophenyl)(phenyl)methyl) amine-precursor in Galodif synthesis-cannot be resolved by this method. However, starting 1-((3-chlorophenyl)(phenyl)methyl) amine quantitatively forms diastereomeric N-((3-chlorophenyl)(phenyl)methyl)-1-camphorsulfonamides in reaction with chiral (1R)-(+)- or (1S)-(-)-camphor-10-sulfonyl chlorides. The diastereomeric ratio of obtained camphorsulfonamides can be easily determined by NMR 1 H and 13 C spectroscopy. The DFT calculations of specific rotation of Galodif enantiomers showed good agreement with experimental data. The absolute configuration of enantiomers was proposed for the first time.

Phenylpropanoids from the fruit of Crataegus pinnatifida exhibit cytotoxicity on hepatic carcinoma cells through apoptosis induction

Eight new phenylpropanoids (1a/1b, 2–4, 5a/5b and 6) including two pairs of enantiomers (1a/1b and 5a/5b), along with a known analogue (7) were isolated from the fruit of Crataegus pinnatifida. Their structures were elucidated using comprehensive spectroscopic methods. Compounds 1a/1b and 5a/5b were separated successfully by chiral chromatographic column. The absolute configurations of enantiomers were determined by comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro antitumor activities of the isolates were evaluated against two human hepatocellular carcinoma HepG2 and Hep3B cells. Five compounds (1a/1b, 2–4) exhibited more potent cytotoxicity and their structure-activity relationships were also discussed. Annexin V-FITC/PI staining using flow cytometry was carried out to examine cell apoptosis, and the results showed that compounds 3–4 with the presence of two methoxy groups substituted at C-3′ significantly induced apoptosis in HepG2 cells.

Benzophenone derivatives from the plant endophytic fungus, Pestalotiopsis sp.

Two new (1–2) and one known (3) benzophenone derivatives, along with five known ambuic acid analogues (4–8) were isolated from the solid cultures of a Pestalotiopsis sp. Compound 2 represented both enantiomeric and atropisomeric isomers, and the absolute configurations of enantiomers [(−)-2 and (+)-2] were determined by electronic circular dichroism (ECD) calculations. All the isolates were evaluated for their antimicrobial and cytotoxic activities. Chlorinated compounds 2 and 3 showed potent antimicrobial activities against four pathogenic bacteria, and compound 3 also displayed strong antifungal activity against Candida glabrata (ATCC 90030) with an MIC50 value of 2.6±0.1μg/mL. Compound 1 exhibited moderate cytotoxicity against U2OS and MCF-7 with IC50 values of 11.6 and 16.8μM, respectively.

LC-MS guided isolation of three pairs of enantiomeric alkaloids from Macleaya cordata and their enantioseparations, antiproliferative activity, apoptosis-inducing property

(±)-Macleayins F–H (1–3), three pairs of new enantiomeric alkaloid dimers, along with four known alkaloids (4–7) as their plausible biogenetic precursors, were isolated from the aerial parts of Macleaya cordata. Compounds 1–3 were obtained under the guidance of LC-MS investigation, and their structures were elucidated by analysis of the 1D and 2D NMR spectroscopic data. The racemic mixtures were successfully separated by chiral HPLC, and the absolute configurations of enantiomers were determined by electronic circular dichroism (ECD) spectroscopy. Compounds 1–7 showed antiproliferative activity against HL-60 with IC50 values of 1.34–41.30 μM, especially compounds 1–2 exhibited the best inhibitory activity against HL-60 cell lines. In addition, the preliminary mechanism investigation for compound 2 using Annexin V/7-AAD double-staining assay, DAPI staining assay and JC-1 staining method, indicated that 2 inhibited cancer cell proliferation potentially through inducing apoptosis via the mitochondria-related pathway and arrested cell cycle of HL-60 cells at S phase.

Alkaloid constituents from Viola tianschanica

Eighteen previously undescribed alkaloids, tishaviolamines A−J, including eight pairs of enantiomers, together with two known benzylisoquinoline alkaloids, (−)-bicuculline and (−)-corlumine, were isolated from Viola tianschanica. Among them, tishaviolamine A−E were demonstrated to possess three types of unpresented skeletons. The structures of these alkaloids were established by comprehensive analyses of the 1D, 2D-NMR and (+)HRESIMS data. The absolute configurations of enantiomers were determined by comparing their calculated ECD spectra with the experimental ones. The menin−mixed lineage leukemia 1 protein−protein interaction inhibitory effect of the isolated compounds were also measured.

Chiral exploration of 6,12-diphenyldibenzo[b,f][1,5]diazocine with stable conformation.

A first optical resolution of 6,12-diphenyldibenzo[b,f][1,5]diazocine with stable boat conformation was achieved by chiral supercritical fluid chromatography (SFC). The absolute configurations of enantiomers were first assigned and determined by X-ray crystal structure based on CIP-rules. The high optical rotation and circular dichroism spectrum were well explained by electronic helix theory. Owing to the high stabilization of boat conformation, the chiral configuration could be maintained at very high temperature, more than 200°C, which was proved by Density Functional Theory calculations.

Interactions between pyrazole derived enantiomers and Chiralcel OJ: Prediction of enantiomer absolute configurations and elution order by molecular dynamics simulations

The separation of enantiomers and confirmation of their absolute configurations is significant in the development of chiral drugs. The interactions between the enantiomers of chiral pyrazole derivative and polysaccharide-based chiral stationary phase cellulose tris(4-methylbenzoate) (Chiralcel OJ) in seven solvents and under different temperature were studied using molecular dynamics simulations. The results show that solvent effect has remarkable influence on the interactions. Structure analysis discloses that the different interactions between two isomers and chiral stationary phase are dependent on the nature of solvents, which may invert the elution order. The computational method in the present study can be used to predict the elution order and the absolute configurations of enantiomers in HPLC separations and therefore would be valuable in development of chiral drugs.

Distinctive effect on nerve growth factor-induced PC12 cell neurite outgrowth by two unique neolignan enantiomers from Illicium merrillianum

Merrillianoid (1), a racemic neolignan possessing the characteristic benzo-2,7-dioxabicyclo[3.2.1]octane moiety, was isolated from the branches and leaves of Illicium merrillianum. Chiral separation of 1 gave two enantiomers (+)−1 and (−)−1. The structure of 1 was established by comprehensive spectroscopic analysis and single crystal X-ray diffraction. The absolute configurations of enantiomers were determined by quantum mechanical calculation. Compound (+)−1 exhibited a better neurotrophic activity than racemate 1 by promoting nerve growth factor (NGF) induced PC12 cell neurite outgrowth, while (−)−1 showed a distinctive inhibitory effect. Furthermore, a mechanism study indicated that the two enantiomers influenced NGF-induced neurite outgrowth of PC12 cells possibly by interacting with the trkA receptor, and extracellular signal regulated kinases 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) in Ras/ERK signal cascade. But the phosphorylation level of serine/threonine kinase Akt1 and Akt2 in PI3K/Akt signal pathway showed no significant difference between (+)−1 and (−)−1.

ChemInform Abstract: Structure and Absolute Configuration of Penicilliumine, a New Alkaloid from Penicillium commune 366606.

Penicilliumine (1), a new structure was isolated from the fermentation Penicillium commune 366606, a marine-derived fungus isolated from the sea water collected at Qingdao, China. HPLC chiral separation of 1 afforded two enantiomers (-)-penicilliumine and (+)-penicilliumine, respectively. The structure of 1 was established by comprehensive spectroscopic data, and single-crystal X-ray diffraction. The absolute configuration of enantiomers was determined by quantum mechanical computation of electronic circular dichroism (ECD). (C) 2014 Elsevier Ltd. All rights reserved.

Structure and absolute configuration of penicilliumine, a new alkaloid from Penicillium commune 366606

Penicilliumine (1), a new structure was isolated from the fermentation Penicillium commune 366606, a marine-derived fungus isolated from the sea water collected at Qingdao, China. HPLC chiral separation of 1 afforded two enantiomers (−)-penicilliumine and (+)-penicilliumine, respectively. The structure of 1 was established by comprehensive spectroscopic data, and single-crystal X-ray diffraction. The absolute configuration of enantiomers was determined by quantum mechanical computation of electronic circular dichroism (ECD).

Peniphenones A–D from the Mangrove Fungus Penicillium dipodomyicola HN4-3A as Inhibitors of Mycobacterium tuberculosis Phosphatase MptpB

A pair of unusual benzannulated 6,6-spiroketal enantiomers [(-)-1 and (+)-1] and three new biogenetically related compounds (2-4), together with two known related analogues (5 and 6), have been isolated from a mangrove fungus, Penicillium dipodomyicola HN4-3A. Their structures were elucidated on the basis of spectroscopic analysis (1D and 2D NMR data) and X-ray crystallography. The absolute configurations of enantiomers (-)-1 and (+)-1 were determined using quantum chemical calculations of the electronic circular dichroic (ECD) spectra. Compounds 2 and 3 exhibited strong inhibitory activity against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with IC50 values of 0.16±0.02 and 1.37±0.05 μM, respectively.

Incarvilleatone, a New Cyclohexylethanoid Dimer from Incarvillea younghusbandii and Its Inhibition against Nitric Oxide (NO) Release

Incarvilleatone (1), an unprecedented dimeric cyclohexylethanoid analog with a racemic nature, was isolated from the whole plant of Incarvillea younghusbandii. HPLC chiral separation of 1 gave two enantiomers (-)-incarvilleatone and (+)-incarvilleatone. The structure of 1 was established by spectroscopic methods and single crystal X-ray diffraction. The absolute configurations of enantiomers were determined by quantum mechanical calculation. (-)-Incarvilleatone exhibited a potent inhibitory effect against NO production in LPS-induced RAW264.7 macrophages.

Aryl[2.2]paracyclophane‐Based Chiral Regioisomeric Analogs of Salicyl Aldehyde: Novel Sources for Construction of Phenoxy‐Imine Ligands

AbstractThe efficient, high‐yield approaches to two novel regioisomeric salicyl aldehyde analogs, 4‐formyl‐13‐(2‐hydroxyphenyl)‐[2.2]paracyclophane and 4‐formyl‐12‐(2‐hydroxyphenyl)‐[2.2]paracyclophane (iso‐FHPhPC and pseudo‐FHPhPC, respectively), constructed on the basis of an aryl[2.2]paracyclophane backbone are described. The key stage of the backbone formation is the Suzuki cross‐coupling of paracyclophanyl halides with arylboronic acids. Efficient procedures for the resolution of the racemic hydroxy aldehydes into enantiomers via Schiff bases with enantiomers of α‐phenylethyl amine were elaborated, and the absolute configurations of enantiomers were established on the basis of X‐ray analysis of diastereomeric imines. Starting from these chiral hydroxy aldehydes the first representatives of bi‐, tri‐, and tetradentate phenoxy‐imine ligands belonging to an aryl[2.2]paracyclophane family were obtained. The induction power of the ligands was tested in the Et2Zn asymmetric addition to aldehydes.

Enantioselectivity in Zebrafish Embryo Toxicity of the Insecticide Acetofenate

Enantioselectivity in separation and toxicology of chiral xenobiotics have become one of the frontier topics interfacing chemistry and toxicology. In this study, enantiomers of insecticide acetofenate (AF) were separated on selected chiral columns by HPLC, and enantioselectivity in developmental toxicity was evaluated using the zebrafish embryo-larval assays. The AF enantiomers were baseline separated on Chiralcel OD, Chiralpak AD, and Sumichiral OA-2500I columns under optimized conditions. Pure enantiomers were obtained on Chiralcel OD. Optical rotatory dispersion (ORD) and circular dichroism (CD) detectors were used to determine the elution order and CD spectra of the enantiomers. The absolute configuration of enantiomers was identified as S-(+)-AF and R-(-)-AF by the octant rule from force-field calculations and CD spectra. The individual enantiomers were used in 4-day zebrafish embryo-larval bioassays, and a series of developmental end points were measured and compared. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate the expressions of estrogen receptor alpha (ERalpha) in zebrafish embryo exposed to varying enantiomers. While the enantiomers showed no difference in acute toxicity, significant enantioselectivity was observed in developmental toxicities such as yolk sac edema and pericardial edema. The data of qRT-PCR showed that there was about 3.2-fold induction in the mRNA levels of ERalpha between fish exposed to (+)-AF and (-)-AF. The results suggest that enantioselectivity may occur at the developmental level even in the absence of selective acute toxicity and should be considered when evaluating ecotoxicological effects of chiral contaminants.

Synthesis and the Absolute Configurations of Isoflavanone Enantiomers

Isoflavanone has been synthesized from the reduction of isoflavone in nearly quantitative yield. Isoflavone with seven equivalents of ammonium formate in the presence of Pd/C in ethanol under atmosphere exclusively produced the two-electron reduced product in two hours. It was characterized by various spectroscopic methods, including UV-VIS, EI-MS, -NMR, -NMR and , -COSY. The racemic mixture was separated by Sumi-Chiral column chromatography and the absolute configurations of the enantiomers were characterized by circular dichroism spectroscopy.

Preparative enantiomeric separation of potent AMP-activated protein kinase activator by HPLC on amylose-based chiral stationary phase: Determination of enantiomeric purity and assignment of absolute configuration

The development of high performance liquid chromatography method on amylose-based stationary phases (Chiralpak AD) has permitted to achieve the preparative enantioseparation of one benzimidazole derivative, potent-AMP-kinase (AMPK) activator with satisfactory yields. Analytical enantioseparation method was optimized and validated to determine the enantiomeric purity. Using the UV detection, repeatability, limits of detection (LD) and quantification (LQ) were determined. Single-crystal X-ray analysis was successful to determine the absolute configuration of the individual enantiomers. A relation between the retention order and the absolute configuration of the enantiomers was established.