Linalool and lilac aldehyde/alcohol in flower scents. Electrophysiological detection of lilac aldehyde stereoisomers by a moth

The stereoisomers of linalool and lilac aldehyde/alcohol were determined in the flower scent of 15 plant species using enantioselective multidimensional gas chromatography/mass spectrometry (enantio-MDGC/MS). Both linalool and all 8 stereoisomers of lilac alcohol and lilac aldehyde were detected, and there was a species-specific pattern. Single stereoisomers were collected by micropreparative-enantio-MDGC and were electrophysiologically tested on antennae of the noctuid moth Hadena bicruris, a species known to rely on lilac aldehyde for finding its host plant. The moth responded to all 8 stereoisomers, though only four stereoisomers were found in the scent of its host plant. The moth was less sensitive to some isomers than to others.     

Synthesis and sensory evaluation of all stereoisomers of sedanolide

Synthesis and sensory evaluation of all stereoisomers of sedanolide (1) are described. The asymmetric synthesis was achieved with using the all stereoisomers of bromoalcohol (3) prepared by enzymatic resolution and inversion of the secondary alcohol. All four stereoisomers of 1 were obtained in high enantiomeric purities (>99% ee). Their sensory evaluation revealed that there were distinct differences among the stereoisomers.     

高异三尖杉酯碱的合成及其立体异构体的分离鉴定

2-氧代-6-甲基庚酰基三尖杉碱(3)与0-(1-甲氧基异丙基)羟基乙酸甲酯(4)在强碱性试剂二异丙胺锂(LDA)存在下,起亲核加成反应,反应中间体5在室温用酸性丙酮水解,得到一种新的三尖杉酯类生物碱一一高异三尖杉酯碱(6c)及其立体异构体(6a、6b、6d)的混合物,产率56%、通过制备薄层层析分得这四个立体异构体,它们的1H NMR和异三尖杉酯碱及其立体异构体的1H NMR类似,推定了它们的绝对构型。初步药理试验表明,高异三尖杉酯碱及其立体异构体的混合物对白血病L7712的DNA合成有明显的抑制作用。     

Analytical and semipreparative chiral separation of cis‐itraconazole on cellulose stationary phases by high‐performance liquid chromatography

cis‐Itraconazole is a chiral antifungal drug administered as a racemate. The knowledge of properties of individual cis‐itraconazole stereoisomers is vital information for medicine and biosciences as different stereoisomers of cis‐itraconazole may possess different affinity to certain biological pathways in the human body. For this purpose, either chiral synthesis of enantiomers or chiral separation of racemate can be used. This paper presents a two‐step high‐performance liquid chromatography approach for the semipreparative isolation of four stereoisomers (two enantiomeric pairs) of itraconazole using polysaccharide stationary phases and volatile organic mobile phases without additives in isocratic mode. The approach used involves the separation of the racemate into three fractions (i.e. two pure stereoisomers and one mixed fraction containing the remaining two stereoisomers) in the first run and consequent separation of the collected mixed fraction in the second one. For this purpose, combination of cellulose tris‐(4‐methylbenzoate) and cellulose tris‐(3,5‐dimehylphenylcarbamate) columns with complementary selectivity for cis‐itraconazole provided full separation of all four stereoisomers (with purity of each isomer > 97%). The stereoisomers were collected, their optical rotation determined and their identity confirmed based on the results of a previously published study. Pure separated stereoisomers are subjected to further biological studies.     

Cyclic hemiacetal and acyclic chain — the two forms of serricornin

The actual structures of the four stereoisomers of serricornin were examined by the X-ray analysis and high-field pmr spectroscopy. Each of the stereoisomers assumes either or both of two forms, cyclic hemiacetal and acyclic chain, in solution.     

5,6-二亚甲基二环[2.2.1]庚-2-醇的四种立体异构体的合成与构型

本文报道了手性桥环化合物5,6-二亚甲基二环[2.2.1]庚-2-醇的四种光学纯立体异构体的合成及其比旋光度[α]~D, 并通过它们之间的相互关系, 确定了它们的绝对构型.     

High‐performance liquid chromatographic separations of stereoisomers of chiral basic agrochemicals with polysaccharide‐based chiral columns and polar organic mobile phases

The separation of the stereoisomers of 23 chiral basic agrochemicals was studied on six different polysaccharide‐based chiral columns in high‐performance liquid chromatography with various polar organic mobile phases. Along with the successful separation of analyte stereoisomers, emphasis was placed on the effect of the chiral selector and mobile phase composition on the elution order of stereoisomers. The interesting phenomenon of reversal of enantiomer/stereoisomer elution order function of the polysaccharide backbone (cellulose or amylose), type of derivative (carbamate or benzoate), nature, and position of the substituent(s) in the phenylcarbamate moiety (methyl or chloro) and the nature of the mobile phase was observed. For several of the analytes containing two chiral centers all four stereoisomers were resolved with at least one chiral selector/mobile phase combination.     

Enantioseparation of palonosetron hydrochloride by micellar electrokinetic chromatography with sodium cholate as chiral selector

The enantioseparation of four stereoisomers of palonosetron hydrochloride by micellar electrokinetic chromatography using sodium cholate as chiral surfactant was described. Sodium cholate was shown to be effective in separating palonosetron hydrochloride stereoisomers. For method optimization, several parameters such as sodium cholate concentration, buffer pH and concentration, the types and concentration of organic modifiers and applied voltage, on the enantioseparation were evaluated and the optimum conditions were obtained as follows: 30 mM borate buffer (pH 9.40) containing 70 mM sodium cholate and 20% (v/v) methanol with an applied voltage of 20 kV. Under these conditions, baseline separation of palonosetron hydrochloride stereoisomers was achieved within 18 min.     

Syntheses of cystothiazole A and its stereoisomers: importance of stereochemistry for antifungal activity

The enantiocontrolled total syntheses of all the stereoisomers of a myxobacterial antibiotic, cystothiazole A, are described. The natural syn stereochemistry at the C4-C5 position was controlled by the asymmetric Evans aldol process, whereas the anti relationship was introduced by a modified Evans aldol methodology. Starting with a known aldehyde, the common substrate of the aldol reactions, cystothiazole A and its three stereoisomers were synthesized in 9 steps. All three stereoisomers did not show antifungal activity even at a dosage 2500-fold that of cystothiazole A.     

两种立体构型的1,3,5,-三-α-萘基苯的合成

通过Adole反应和Grigard反应合成了相应的两种立体异构的1,3,5-三-α-萘基苯. 报道了它们的UV, IR, FD-MS和NMR . 论了两种异构体的^1H NMR 和^1^3C NMR的区别.     

Catalytic asymmetric synthesis of stereoisomers of 1-C-n-butyl-LABs for the SAR study of α-glucosidase inhibition

We achieved synthesis of seven stereoisomers of 1-C-n-butyl-L-iminofuranose derivatives using catalytic asymmetric alkylation and Negishi coupling as key reactions. The synthetic strategy based on these key reactions was quite useful, since both α- and β-iminofuranoses could be obtained by switching the chirality of the ligand employed for the AAA reaction. The common intermediates for α- and β-isomers were subjected to further manipulations to install a diol unit at C2 and C3 to give the desired stereoisomers of L-iminofuranose derivatives. We achieved the preparation of all stereoisomers of 1-C-n-butyl-L-iminofuranose derivatives, with the exception of β-lyxo type iminofuranose. It is noteworthy that a synthetic route for many stereoisomers of iminofuranose derivatives was developed. Unfortunately, none of the L-iminofuranoses obtained showed inhibitory activity against the α-glycosidases examined—e.g., maltase, sucrase, and isomaltase.     

Stereoselective determination of allethrin by two-dimensional achiral/chiral liquid chromatography with ultraviolet/circular dichroism detection

A two-dimensional achiral/chiral HPLC method with circular dichroism (CD) detection was optimized for the stereochemical resolution and determination of the elution order of the eight stereoisomers of synthetic allethrin. A monolithic silica HPLC column (Chromolith, Merck, 100 mm x 4.6 mm i.d.) was put orthogonally to an enantioselective OJ Daicel column (250 mm x 4.6 mm i.d.) by means of a switching valve. The resolution of cis and trans diastereoisomers on the silica column was obtained by using a mobile phase consisting of n-hexane:tert-butyl methyl ether (96:4) (v/v) at a flow rate of 1 ml min(-1). The cis and trans peaks were then switched to the enantioselective OJ column separately in two subsequent injections. The resolution of the four trans stereoisomers was accomplished by using n-hexane:tert-butyl methyl ether (90:10) (v/v), while the mobile phase composition for the four cis stereoisomers consisted of n-hexane:isopropanol (99.3:0.7) (v/v). The CD based detection system allowed the determination of the elution order on the basis of the CD signals of the single stereoisomers, together with the injection of pure stereoisomers. Under the final conditions, the validated method was applied to the determination of stereoisomeric composition and absolute configuration of the prevailing stereoisomers of real samples, i.e. commercial batches of different sources of d-allethrin.     

Rhodium-catalyzed reductive cyclization of 1,6-enynes and stereoselective synthesis of the putative structure of lucentamycin A and its stereoisomers

A Rh-catalyzed diastereoselective reductive cyclization, mediated by hydrogen, of optically active 1,6-enynes using chiral BINAP was successfully applied to the total synthesis of four stereoisomers of the proposed structure of lucentamycin A. In order to synthesize two of these four stereoisomers, we successfully constructed chiral proline derivatives bearing cis-carbon substituents at C2 and C3 positions based on Krische’s methodology, which has very rarely been reported. Anti-proliferative activities on HCT-116 cell line and NMR data of these four stereoisomers were compared with those of naturally occurring lucentamycine A. The results show that the proposed structure of lucentamycin A needs revision.     

Stereochemistry of heterocycles

Twenty-eight previously unreported compounds of the 4,5-dialkyl-, 4,5,5-trialkyl-, 2,2,4-trimethyl-5-alkyl, and 2,2,4-trimethyl-5,5-dialkyl-1,3-dioxane series, including 24 individual cis and trans isomers, obtained with a purity of the order of 85–99% by fractionation of the starting mixtures of stereoisomers with total condensation columns, were synthesized. The applicability of the Cram rule, modified for compounds with complexforming groups, for the estimation of the possible configurations and conformations of the stereoisomers of the examined series was demonstrated. The cis configuration of the lowboiling stereoisomers and the trans configuration of the high-boiling stereoisomers were proved by NMR spectroscopy; the investigated compounds exist predominantly in the chair conformation. The 5-C-axial position is preferred over the 4-C-axial conformation in the examined series of compounds. The synthesis and hydrolysis of the examined 1,3-dioxanes proceed without involvement of the steric centers of the molecules, and the configurations of the corresponding diastereomeric 1,3-diols can be established on the basis of data on the configurations of the 1,3-dioxanes. The IR spectra of the stereoisomers of the examined series of compounds were studied, and the spectral characteristics of the trans and cis isomers, respectively, were found.See [30] for communication XII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 893–904, July, 1971.     

Assignment of absolute configurations of permethrin and its synthon 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid by electronic circular dichroism,optical rotation,and X-ray crystallography

The availability of single stereoisomers of biologically/toxicologically relevant chiral compounds such as the pyrethroid-type insecticide permethrin (PM) and the reliable determination of their absolute configurations are of central importance for the detailed investigation and correct assignment of stereoselective effects. In this context, single stereoisomers of 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (DCCA), a precursor, metabolite, and environmental degradation product of PM, were isolated from a mixture of all four stereoisomers in enantiomeric excesses of >99% via a two-step chromatographic process combining a diastereoselective reversed-phase separation in the first step with a direct enantiomer separation in the second step. Esterification of DCCA stereoisomers with 3-phenoxybenzyl alcohol yielded PM. Electronic circular dichroism (ECD) spectra of DCCA and PM stereoisomers were measured in non-polar (cyclohexane containing 5% v/v 1,2-dichloroethane) and non-protic polar (acetonitrile) solvents. Cotton effects suitable to distinguish the four stereoisomers of each DCCA and PM were obtained. Absolute configurations of DCCA were determined by confrontation of calculated (time-dependent density-functional theory using B3LYP hybrid functional) and experimental ECD and optical rotation (OR) data. Fully convergent results between ECD and X-ray diffractometry (analysis of DCCA isomers co-crystallized with O-9-(2,6-diisopropylphenylcarbamoyl)quinine), which was employed as a reference method, were obtained. The importance of considering dimer formation of DCCA in solution for the computational delineation of absolute configurations was demonstrated by (1R,3R)-cis-DCCA for which the ΔG Boltzmann averaged calculated monomeric form delivered the opposite sign of OR compared to the dimeric form and the value determined experimentally in dichloromethane. For (1S,3R)-trans-DCCA both monomer and dimer delivered the identical sign of OR and this was in agreement with the experimental measurement. In contrast to OR, the calculated ECD spectra of these two DCCA stereoisomers were less sensitive toward intermolecular association.     

Enantioselective CE–MS analysis of ketamine metabolites in urine

The chiral drug ketamine has long-lasting antidepressant effects with a fast onset and is also suitable to treat patients with therapy-resistant depression. The metabolite hydroxynorketamine (HNK) plays an important role in the antidepressant mechanism of action. Hydroxylation at the cyclohexanone ring occurs at positions 4, 5, and 6 and produces a total of 12 stereoisomers. Among those, the four 6HNK stereoisomers have the strongest antidepressant effects. Capillary electrophoresis with highly sulfated γ-cyclodextrin (CD) as a chiral selector in combination with mass spectrometry (MS) was used to develop a method for the enantioselective analysis of HNK stereoisomers with a special focus on the 6HNK stereoisomers. The partial filling approach was applied in order to avoid contamination of the MS with the chiral selector. Concentration of the chiral selector and the length of the separation zone were optimized. With 5% highly sulfated γ-CD in 20 mM ammonium formate with 10% formic acid and a 75% filling the four 6HNK stereoisomers could be separated with a resolution between 0.79 and 3.17. The method was applied to analyze fractionated equine urine collected after a ketamine infusion and to screen the fractions as well as unfractionated urine for the parent drug ketamine and other metabolites, including norketamine and dehydronorketamine.     

Divergent syntheses of all 16 carbasugar stereoisomers via stereoconversion of carba-β-d-altropyranose derivatives

We have developed practical synthetic routes to enantiopure d- and l-carba-β-altrose derivatives and all the possible stereoisomers via their divergent stereoconversions. Carba-β-d-altrose was prepared from 3-cyclohexene-1-carboxylic acid and converted to carba-β-d-mannose, carba-β-d-idose, and carba-β-d-talose derivatives via regio- and stereoselective oxidation/reduction of 3-OH and/or 4-OH. The four carbasugar stereoisomers were then transformed to the remaining 12 carbasugar stereoisomers and their 1,2-epoxides by regio- and stereoselective manipulation of hydroxyl groups in C1 and C2, which includes oxidation/reduction, Mitsunobu’s reaction, olefination/dihydroxylation, and epoxidation/ring-opening protocols.     

A modular synthetic approach toward exhaustively stereodiversified ligand libraries

[structure] This report describes a modular approach to the synthesis of stereodiversified natural product-like libraries. Monomers 2 and 3 were coupled in parallel by silyl-tethered olefin metathesis to generate all 16 stereoisomers of cis-enediols 1. All 16 stereoisomers were incorporated into chimerae having flanking peptidic segments. These chimerae exhibited a broad range of hydrophobicities, raising the possibility that stereochemical variation might be used to tune the pharmacologic properties of small molecules.     

Isolation,anticholinesterase properties and acute toxicity of the four stereoisomers of the nerve agent soman

Abstract

The four stereoisomers of pinacolyl methylphospho-nofluoridate (soman) were isolated with more than 99% optical purity. The bimolecular rate constants for inhibition of electric eel acetylcholinesterase and the LD₅₀-values (sc, mice) of the stereoisomers were determined.     

双丙酮-D-甘露糖醇—硼酸络合酸手性毛细管电泳法分离盐酸莱克多巴胺立体异构体

采用手性多羟基化合物—硼酸络合酸为手性选择剂,建立了分离盐酸莱克多巴胺4个立体异构体的手性毛细管电泳(NACE)方法。实验考察了手性选择剂的种类、浓度和三乙胺浓度对手性分离效果的影响。结果表明,双丙酮-D-甘露糖醇—硼酸络合酸手性选择剂的分离效果最好,优化的缓冲溶液组成为含100 mmol/L双丙酮-D-甘露糖醇、100 mmol/L硼酸和72 mmol/L三乙胺的甲醇溶液。在优化的实验条件下,盐酸莱克多巴胺的4个立体异构体均可以达到基线分离,质量浓度在6.2~200.0μg/mL范围内与峰面积分别呈现良好的线性关系,检测限和定量限分别为0.6μg/mL和2.0μg/mL,加标回收率为97.5%~102.5%,饲料中的提取回收率为66.4%~72.5%。方法可用于盐酸莱克多巴胺4个立体异构体的手性分离和含量测定。