Determination of the Absolute Configuration of (−)‐Mirtazapine by Vibrational Circular Dichroism

The absolute configuration of the (−)‐enantiomer of mirtazapine was determined by means of vibrational circular dichroism (VCD). The observed VCD of (−)‐mirtazapine showed excellent correlation with the calculated VCD of the (R)‐enantiomer. This is in agreement with the absolute configuration as determined by independent synthesis starting from (R)‐phenylglycine.     

Enantiomeric high‐performance liquid chromatography resolution and absolute configuration of 6β‐benzoyloxy‐3α‐tropanol

The absolute configuration of the naturally occurring isomers of 6β‐benzoyloxy‐3α‐tropanol ( 1 ) has been established by the combined use of chiral high‐performance liquid chromatography with electronic circular dichroism detection and optical rotation detection. For this purpose (±)‐ 1 , prepared in two steps from racemic 6‐hydroxytropinone ( 4 ), was subjected to chiral high‐performance liquid chromatography with electronic circular dichroism and optical rotation detection allowing the online measurement of both chiroptical properties for each enantiomer, which in turn were compared with the corresponding values obtained from density functional theory calculations. In an independent approach, preparative high‐performance liquid chromatography separation using an automatic fraction collector, yielded an enantiopure sample of _OR(+)‐ 1 whose vibrational circular dichroism spectrum allowed its absolute configuration assignment when the bands in the 1100–950 cm^‐1 region were compared with those of the enantiomers of esters derived from 3α,6β‐tropanediol. In addition, an enantiomerically enriched sample of 4 , instead of _OR(±)‐ 4 , was used for the same transformation sequence, whose high‐performance liquid chromatography follow‐up allowed their spectroscopic correlation. All evidences lead to the _OR(+)‐(1S,3R,5S,6R) and _OR(?)‐(1R,3S,5R,6S) absolute configurations, from where it follows that samples of 1 isolated from Knightia strobilina and Erythroxylum zambesiacum have the _OR(+)‐(1S,3R,5S,6R) absolute configuration, while the sample obtained from E. rotundifolium has the _OR(?)‐(1R,3S,5R,6S) absolute configuration.     

Characterization of stereoisomeric 5‐(2‐nitro‐1‐phenylethyl)furan‐2(5H)‐ones by computation of 1H and 13C NMR chemical shifts and electronic circular dichroism spectra

In the present work, we describe the preparation of two diastereomers from the enantioselective Michael addition of furan‐2(5H)‐one to (E)‐(2‐nitrovinyl)benzene catalyzed by a dinuclear Zn‐complex. The relative configurations of the diastereomeric products were assigned by comparing nuclear magnetic resonance (NMR) experimental chemical shift data with those computed by density functional theory (DFT) methods. Corrected mean absolute error (CMAE) and CP3 analyses were used to compare the data sets. The absolute configuration of each diastereomer was initially assigned by analysis of electronic circular dichroism (ECD) data, which was consistent with that of the known X‐ray crystallographic structure of the product of a related reaction, namely, (R)‐5‐((R)‐1‐(4‐chlorophenyl)‐2‐nitroethyl)furan‐2(5H)‐one.     

Structure and absolute configuration of hydroxy‐bis‐dihydrofarinosin from Encelia farinosa

The structure of the dimeric eudesmanolide hydroxy‐bis‐dihydrofarinosin ( 1 ) from Encelia farinosa followed after contrasting their ¹H and ¹³C NMR spectra with those of encelin ( 6 ), hydroxy‐bis‐dihydroencelin ( 3 ), and farinosin ( 4 ). Structure  1 was verified by single‐crystal X‐ray diffraction analysis, which further provided the stereochemistry of the hydroxy group at C‐4. Comparison of the experimental vibrational circular dichroism spectrum of its derived diacetate 2 with that calculated by density functional theory provided the absolute configuration, which resulted the same as that of its biogenetic precursor 4 . Evaluation of several chemical shift differences between the two eudesmanolide fragments of 1 and 3 allows also ascertaining the yet not reported absolute configuration of the C‐4 stereogenic center of 3 . Copyright © 2016 John Wiley & Sons, Ltd.     

Synthesis,properties and solid state structure of 5‐diphenylphosphino‐2‐hydroxy‐1,3‐xylyl‐18‐crown‐5

5‐Diphenylphosphino‐2‐hydroxy‐1,3‐xylyl‐18‐crown‐5 has been synthesized from 5‐bromo‐2‐hydroxy‐18‐crown‐5 by reacting it in sequence at low temperature with n‐butyl lithium and methyl diphenylphosphonite. The phosphorous donor properties of this phenol phosphine (OH derivative) and the corresponding phenoxide (O^? derivative) have been studied in the presence and absence of alkali metal ions by determining the frequencies of the A₁ ν(CO) bands of Ni(CO)₃L complexes. For the OH and O^? derivatives, the latter generated by addition of CsOH to the former, the ν(CO) bands are observed at 2067.6 and 2063.4 cm^?1, respectively, providing the trend predicted by Hammett parameters for OH and O^? substituents. Addition of Na⁺ or K⁺ to the OH derivative has little effect on this stretching frequency, but the former ion shifts the O^? derivative band to 2067.7 cm^?1 A solid state structure has been obtained of the OH derivative, and two independent molecules were found in the unit cell. Both have a single water molecule hydrogen bonded to two across‐ring oxygen atoms and the phenol hydrogen. The crown ether ring has the usual gauche and anti arrangements for the C‐C and C? O bonds.     

Spectrum–Structure Relationship in Carbohydrate Vibrational Circular Dichroism and Its Application to Glycoconjugates

Preliminary reports of the nature of the vibrational circular dichroism (VCD) peak at around 1145 cm^?1, which is characteristic of axial glycosidic sugars and is called the glycoside band (J. Am. Chem. Soc. 2004 , 126, 9496), have been throughly examined. Through systematic carbohydrate measurements, it was found that the sign of the glycoside band reflects not only the anomeric configuration but also the pyranose conformation. Isotope and theoretical studies characterized its vibrational mode as C1–H1 deformation coupled with C1–O1 stretching, which indicates its applicability to more‐complicated glycoconjugates. In this study, for the first time, carbohydrate VCD spectra were reliably predicted by means of density functional theory (DFT) calculations. The VCD technique was applied to glycopeptides, and simultaneous analysis of both the carbohydrate and aglycan parts was carried out.     

Synthesis,Characterization, and Application of Platinum(II) Complexes Incorporating Racemic and Optically Active 4‐Chloro‐5‐Methyl‐1‐Phenyl‐1,2,3,6‐Tetrahydrophosphinine Ligand

An efficient resolution method was elaborated for the preparation of (+)‐4‐chloro‐5‐methyl‐1‐phenyl‐1,2,3,6‐tetrahydrophosphinine oxide using the acidic Ca²⁺ salt of (–)‐O,O‐di‐p‐toluoyl‐(2R,3R)‐tartaric acid. Crystal structure of the diastereomeric complex was evaluated by single crystal X‐ray analysis. Beside this, the absolute P‐configuration was also determined by a circular dichroism (CD) spectroscopic study including theoretical calculations. The tetrahydrophosphinine oxide was then converted to the corresponding platinum complex whose stereostructure was investigated by high‐level quantum chemical calculations. The Pt complex was tested as a catalyst in the hydroformylation of styrene.     

Synthesis and Stereochemical Assignment of Crypto‐Optically Active 2H6‐Neopentane

The determination of the absolute configuration of chiral molecules is at the heart of asymmetric synthesis. Here we probe the spectroscopic limits for chiral discrimination with NMR spectroscopy in chiral aligned media and with vibrational circular dichroism spectroscopy of the sixfold‐deuterated chiral neopentane. The study of this compound presents formidable challenges since its stereogenicity is only due to small mass differences. For this purpose, we selectively prepared both enantiomers of ²H₆‐ 1 through a concise synthesis utilizing multifunctional intermediates. While NMR spectroscopy in chiral aligned media could be used to characterize the precursors to ²H₆‐ 1 , the final assignment could only be accomplished with VCD spectroscopy, despite the fleetingly small dichroic properties of 1 . Both enantiomers were assigned by matching the VCD spectra with those computed with density functional theory.     

New synthesis on the basis 2‐allyloxy chalcone and NMR studies its some derivatives

Synthesis and NMR investigations of cyclohexenone, flavanone, isoxazol and indazole derivatives of (2E)‐3‐[2‐(allyloxy)‐5‐bromophenyl]‐1‐(2‐hydroxy‐5‐methylphenyl)‐2‐propen‐1‐one ( I , chalcone) have been carried out. The results confirm the formation of O–H???O type intramolecular hydrogen bond and intramolecular cyclization in the (2E)‐3‐[2‐(allyloxy)‐5‐bromophenyl]‐1‐(2‐hydroxy‐5‐methylphenyl)‐2‐propen‐1‐one ( I ), the presence of conformational and keto–enol tautomeric transitions in the 6‐acetyl‐5‐[2‐(allyloxy)‐5‐bromophenyl]‐3‐(2‐hydroxy‐5‐methylphenyl)‐2‐cyclohexen‐1‐one ( II ), conformational transitions in the 2‐{4‐[2‐(allyloxy)‐5‐bromophenyl]‐3‐methyl‐4.5‐dihydro‐1.2‐benzisoxazol‐6‐yl}‐4‐methylphenol ( III ) and 2‐{4‐[2‐(allyloxy)‐5‐bromophenyl]‐3‐methyl‐4.5‐dihydro‐1H‐indazol‐6‐yl}‐4‐methylphenol ( IV ). The conformational and keto–enol tautomerism in the investigated compounds have been also confirmed by chemical methods. Copyright © 2014 John Wiley & Sons, Ltd.     

A Facile Method to Determine the Absolute Structure of Achiral Molecules: Supramolecular‐Tilt Structures

Achiral compounds 4‐methoxy‐4‐(p‐methoxyphenyl)cyclohexanoneethylene ketal ( 2 ), 4‐hydroxy‐4‐(p‐methoxy phenyl)cyclohexanoneethylene ketal ( 3 ), and 3,5‐dimethyl‐4‐nitropyrazole ( 4 ) crystallized in chiral structures and the samples showed an enantiomeric excess. We have determined the absolute structures of these compounds by using X‐ray diffraction with copper radiation at low temperatures. Moreover, we have also established the prevalent absolute structures in these samples, by comparing their calculated and solid‐state vibrational circular dichroism (VCD) spectra. The consistency of this method was confirmed by using (R,R)‐2,8‐diiodo‐4,10‐dimethyl‐6 H,12H‐5,11‐methano‐dibenzo[b,f][1,5]diazocine, Tröger′s base, (R,R)‐ 1 , as a chiral compound of known absolute configuration.     

The Absolute Configuration of (+)‐Ethyl cis‐1‐Benzyl‐3‐hydroxypiperidine‐4‐carboxylate and (+)‐4‐Ethyl 1‐Methyl cis‐3‐Hydroxypiperidine‐1,4‐dicarboxylate; a Revision

Discrepancies between chiroptical data from the literature and our determination of the structure of the title compounds (+)‐ 5 and (+)‐ 9a were resolved by an unambiguous assignment of their absolute configuration. Accordingly, the dextrorotatory cis‐3‐hydroxy esters have (3R,4R)‐ and the laevorotatory enantiomers (3S,4S)‐configuration. The final evidences were demonstrated on both enantiomers (+)‐ and (?)‐ 5 by biological reduction of 4 by bakers' yeast and stereoselective [Ru^II(binap)]‐catalyzed hydrogenations of 4 (Scheme 2), by the application of the NMR Mosher method on (+)‐ and (?)‐ 5 (Scheme 3), as well as by the transformation of (+)‐ 5 into a common derivative and chiroptical correlation (Scheme 4).     

Synthesis and Spectra Characteristics of Novel 3‐(para‐Bromophenyl)‐7‐(substituted vinyl) Coumarins

Five new coumarin derivatives ( 5a , 5b , 5c , 5d , 5e ) with extending para‐bromophenyl at the 3‐position and substituted vinyl at the 7‐position were synthesized and characterized by FT‐IR, ¹H NMR, and element analysis. The absorption and fluorescence characteristics of compounds 5a , 5b , 5c , 5d , 5e showed significant dependences on its molecular structure, which possessed large Stokes shifts (up to 8309 cm^?1) and high fluorescence quantum yield (up to 0.80) in CH₂Cl₂. These advantageous spectral properties should allow use in many areas.     

Kinetics of the reactions of OH with 3‐methyl‐2‐cyclohexen‐1‐one and 3,5,5‐trimethyl‐2‐cyclohexen‐1‐one under simulated atmospheric conditions

Relative rate coefficients for the reactions of OH with 3‐methyl‐2‐cyclohexen‐1‐one and 3,5,5‐trimethyl‐2‐cyclohexen‐1‐one have been determined at 298 K and atmospheric pressure by the relative rate technique. OH radicals were generated by the photolysis of methyl nitrite in synthetic air mixtures containing ppm levels of nitric oxide together with the test and reference substrates. The concentrations of the test and reference substrates were followed by gas chromatography. Based on the value k(OH + cyclohexene) = (6.77 ± 1.35) × 10^?11 cm³ molecule^?1 s^?1, rate coefficients for k(OH + 3‐methyl‐2‐cyclohexen‐1‐one) = (3.1 ± 1.0) × 10^?11 and k(OH + 3,5,5‐trimethyl‐2‐cyclohexen‐1‐one) = (2.4 ± 0.7) × 10^?11 cm³ molecule^?1 s^?1 were determined. To test the system we also measured k(OH + isoprene) = (1.11 ± 0.23) × 10^?10 cm³ molecule^?1 s^?1, relative to the value k(OH + (E)‐2‐butene) = (6.4 ± 1.28) × 10^?11 cm³ molecule^?1 s^?1. The results are discussed in terms of structure–activity relationships, and the reactivities of cyclic ketones formed in the photo‐oxidation of monoterpene are estimated. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 34: 7–11, 2002     

Structural,Magnetic, and Computational Correlations of Some Imidazolo‐Fused 1,2,4‐Benzotriazinyl Radicals

1,3,7,8‐Tetraphenyl‐4,8‐dihydro‐1H‐imidazolo[4,5g][1,2,4]benzotriazin‐4‐yl ( 5 ), 8‐(4‐bromophenyl)‐1,3,7‐triphenyl‐4,8‐dihydro‐1H‐imidazolo[4,5g][1,2,4]benzotriazin‐4‐yl ( 6 ), and 8‐(4‐methoxyphenyl)‐1,3,7‐triphenyl‐4,8‐dihydro‐1H‐imidazolo[4,5g][1,2,4]benzotriazin‐4‐yl ( 7 ) were characterized by using X‐ray diffraction crystallography, variable‐temperature magnetic susceptibility studies, and DFT calculations. Radicals 5 – 7 pack in 1 D π stacks made of radical pairs with alternate short and long interplanar distances. The magnetic susceptibility (χ vs. T) of radicals 5 and 6 exhibit broad maxima at (50±2) and (50±4) K, respectively, and are interpreted in terms of an alternating antiferromagnetic Heisenberg linear chain model with average exchange‐interaction values of J=?31.3 and ?35.4 cm^?1 (g_solid=2.0030 and 2.0028) and an alternation parameter a=0.15 and 0.38 for 5 and 6 , respectively. However, radical 7 forms 1 D columns of radical pairs with alternating distances; one of the interplanar distances is significantly longer than the other, which decreases the magnetic dimensionality and leads to discrete dimers with a ferromagnetic exchange interaction between the radicals (2J=23.6 cm^?1, 2zJ′=?2.8 cm^?1, g_solid=2.0028). Magnetic exchange‐coupling interactions in 1,2,4‐benzotriazinyl radicals are sensitive to the degree of slippage and inter‐radical separation, and such subtle changes in structure alter the fine balance between ferro‐ and antiferromagnetic interactions.     

振动圆二色谱在轴手性β-双咔啉N—O衍生物立体化学研究中的应用

采用振动圆二色谱(VCD)方法研究了一个具有高度催化活性的轴手性结构的双咔啉N—O化合物的立体化学结构. 在B3LYP/6-311+G(d)水平上得到的计算结果表明, 对于具有负旋光值的双咔啉N—O化合物化合物, 其绝对构型是aS. 同时, 分别计算了双咔啉N—O化合物的电子圆二色谱(ECD)和旋光值, 并与实验结果进行了比较. 在化合物结构完全正确条件下, VCD, ECD和旋光数据均表明, 具有负旋光值的该化合物的绝对构型是aS.     

Two 17‐hydroxy‐9(10→5)‐abeo‐estr‐4‐ene‐3,10‐diones

(5S,9S,17S)‐17‐Hydroxy‐9(10→5)‐abeo‐estr‐4‐ene‐3,10‐dione, C₁₈H₂₆O₃, (II), and (5R,9R,17S)‐17‐hydroxy‐9(10→5)‐abeo‐estr‐4‐ene‐3,10‐dione, C₁₈H₂₆O₃, (III), are equimolecular products of the Fe^II‐induced transposition of 10β‐hydro­peroxy‐17β‐hydroxyestr‐4‐en‐3‐one, (I). With respect to reagent mol­ecules, the configuration at C9 is retained for (II) while it is inverted in (III). The conformations of the five‐ and six‐membered rings are compared.     

3‐O‐Acetyl‐4‐deoxy‐4‐iodo‐β‐d‐fructo­furan­osyl 2,3,6‐tri‐O‐acetyl‐4‐chloro‐4‐deoxy‐α‐d‐gluco­pyran­oside

At 160 K, the gluco­pyran­osyl ring of the title compound, C₂₀H₂₈ClIO₁₃, has a near‐ideal ⁴C₁ conformation and the fructo­furan­osyl ring has a twist ⁴T₃ conformation. The two hydroxy groups are involved in intra‐ and intermolecular hydrogen bonds, with the latter interactions linking the mol­ecules into infinite one‐dimensional chains. The absolute configuration of the mol­ecule has been determined.     

Synthesis,properties and X‐ray structure of 5‐azido‐2‐methoxy‐1,3‐xylyl‐18‐crown‐5

5‐Azido‐2‐methoxy‐1,3‐xylyl‐18‐crown‐5 has been prepared by reacting p‐toluenesulfonyl azide with the carbanion generated from the reaction of 5‐bromo‐2‐methoxy‐1,3‐xylyl‐18‐crown‐5 with n‐butyl lithium. The asymmetric N₃ stretch of this product has been observed as a single band at 2110 cm^?1 in dichloromethane solution. Addition of solid NaSCN, KSCN and CsSCN shifts this band to 2115, 2113 and 2112 cm^?1, respectively. Computational studies of this azide at the B3LYP‐6‐31G* level in the presence and absence of Na⁺ predicted these bands to be at 2173 cm^?1 and 2184 cm^?1. For the salt‐containing solutions, additional bands were observed at 2066 cm^?1, 2056 cm^?1 and 2055 cm^?1, respectively, which are in the range expected for CN stretches. The X‐ray structure of this azide has been determined. The terminal and internal N? N bond lengths were found to be 1.127(2) and 1.245(2) Δ, respectively, which is the usual pattern for aromatic azides. The crown ether is looped over the face of the aromatic ring resulting in an angle of 38.94° between the plane defined by the aromatic ring and that defined by the five ring oxygen atoms. In addition, the CH₃ group is rotated out of the plane of the phenyl ring with C1‐C18‐O181‐C182 and C17‐C18‐O181‐C182 dihedral angles of 93.81(14)° and ‐90.54(14)°, respectively.     

Design,Preparation of 3‐Hydroxy Isoindolinone Cyclotripeptides,and the In Vitro Antitumor Activities Against Cervical Carcinoma HeLa Cells

Photoinduced single electron transfer cyclization processes for synthesis of a series of 3‐hydroxy isoindolinone cyclotripeptides containing double pharmacophores (cyclotripeptides and phthalimide moiety) are described to develop novel antitumor cyclopeptide drugs. The results showed that our proposed method could be used to synthesize various isoindolinone cyclotripeptides highly regioselectively at a moderate rate. Moreover, the inhibitory potency toward human cervical carcinoma HeLa cells of the target cyclopeptides and the linear tripeptide precursors were evaluated, and most of the compounds were observed with potent inhibition ability against tumor growth. Specifically, compound 6c was found to inhibit HeLa cells with an IC₅₀ value of 32 μM, which may serve as a potential candidate for drug development. In addition, 3‐hydroxy isoindolinone‐cyclo‐Gly‐Ala‐Pro ( 6a ₁ ) was chosen from the obtained cyclopeptides for the absolute configuration research, and an S configuration of C‐3 was established by experimental electronic circular dichroism with the aid of theoretical calculations.     

Synthesis,structure and in vitro cytotoxicity testing of some 2‐aroylbenzofuran‐3‐ols

Five 2‐aroyl‐5‐bromobenzo[b]furan‐3‐ol compounds (two of which are new) and four new 2‐aroyl‐5‐iodobenzo[b]furan‐3‐ol compounds were synthesized starting from salicylic acid. The compounds were characterized by mass spectrometry and ¹H NMR and ¹³C NMR spectroscopy. Single‐crystal X‐ray diffraction studies of four compounds, namely, (5‐bromo‐3‐hydroxybenzofuran‐2‐yl)(4‐fluorophenyl)methanone, C₁₅H₈BrFO₃, (5‐bromo‐3‐hydroxybenzofuran‐2‐yl)(4‐chlorophenyl)methanone, C₁₅H₈BrClO₃, (5‐bromo‐3‐hydroxybenzofuran‐2‐yl)(4‐bromophenyl)methanone, C₁₅H₈Br₂O₃, and (4‐bromophenyl)(3‐hydroxy‐5‐iodobenzofuran‐2‐yl)methanone, C₁₅H₈BrIO₃, were also carried out. The compounds were tested for their in vitro cytotoxicity on the four human cancer cell lines KB, Hep‐G2, Lu‐1 and MCF7. Six compounds show good inhibiting abilities on Hep‐G2 cells, with IC₅₀ values of 1.39–8.03 µM.