Reassigning the stereochemistry of bioactive cepharanthine using calculated versus experimental chiroptical spectroscopies

The absolute configuration of cepharanthine (1), a strongly bioactive bisbenzylisoquinoline alkaloid exhibiting 12 specific bioactivities without any reported negative side-effects, has been reassigned from (1R,1′S) to (1R,1′R) using quantum theory. The absolute configurations (ACs) of 13 other analogues of 1 were also systematically reassigned. Six quaternary salts were prepared from 1 and one exhibited strong anti-bacterial activity against Bacillus subtilis with MIC 0.31?μM, while Ciprofloxacin, the positive control medicine was 3.88?μM. This work established the critical importance of correlating chiroptical experimental spectra with their quantum mechanically predicted spectra for accurate stereogenic center assignments.     

手性物质拉曼光活性(Raman Optical Activity)研究综述

通过对大量文献的调研，本文分四个部分对手性物质的旋光现象及振动光活性进行了较为全面的介绍，重点介绍了拉曼光活性ＲＯＡ（ＲａｍａｎＯｐｔｉｃａｌＡｃｔｉｖｉｔｙ）产生机理、研究状况及对其研究的意义。     

A combined theoretical and experimental study of the structure and vibrational absorption, vibrational circular dichroism, Raman and Raman optical activity spectra of the L-histidine zwitterion

A combined theoretical and experimental study of the vibrational absorption (VA)/IR, vibrational circular dichroism (VCD), Raman and Raman optical activity (ROA) spectra of l-histidine in aqueous solution has been undertaken to answer the questions (i) what are the species present and (ii) which conformers of the species are present under various experimental conditions. The VA spectra of l-histidine have been measured in aqueous solution and the spectral bands which can be used to identify both species (cation, zwitterion, anion) and conformer of the species have been identified and subsequently used to identify the species (zwitterion) and conformer (gauche minus minus, gauche minus plus for the side chain dihedral angles) present in solution at pH 7.6. The VCD spectral intensities have been used subsequently in combination with further theoretical studies to confirm the conclusions that have been arrived at by only analyzing the VA/IR spectra. Finally a comparison of measured Raman and ROA spectra of l-histidine with Raman and ROA spectral simulations for the conformers and species derived from the combined VA/IR and VCD experimental and theoretical work is presented as a validation of the conclusions arrived at from VA/IR and VCD spectroscopy. The combination of VA/IR and VCD with Raman and ROA is clearly superior and both sets of experiments should be performed.     

A Spectroscopic Study of Colchicine in the Solid State and in Solution by Multinuclear Magnetic Resonance and Vibrational Circular Dichroism

Although almost 200‐years‐old, several unknown aspects remain to be explored of colchicine, the unique available drug for acute flares of gout. In this article, we report density‐functional theory (DFT) studies of geometry, energy, and NMR; ¹H‐, ¹³C‐, and ¹⁵N‐NMR chemical shifts and some spin‐spin coupling constants, including the complete analysis of the saturated part (ring B); the assignment of both enantiomers by NMR using a chiral solvating agent; solid‐state NMR experiments of the different forms of natural and racemic colchicine, and IR and vibrational circular dichroism (VCD) studies of these same forms.     

A structure and an absolute configuration of (+)-alternamin, a new coumarin from Murraya alternans having antidote activity against snake venom

(+)-Alternamin (1), a new dihydrofuranocoumarin, was isolated from the aerial parts of Murraya alternans (Kurz) Swingle. The analysis 2-D NMR correlation of (+)-1 led to either of linear dihydrofuranocoumarin (2A, 2C) or angular one (2B). An IR and a vibrational circular dichroism (VCD) studies were conducted to distinguish the structure and to assign the absolute configuration. By comparison of the observed spectra with the calculated spectra for (S)-2A, (S)-2B, and (R)-2C, the molecular structure of (+)-1 was determined to be (S)-(+)-5,8-dimethoxymarmesin. The compound exhibited antidote activity against snake venom from Trimeresurus flavoviridis, affording experimental support for the pharmacological use of M. alternans.     

The exopolyhedral ligand orientation (ELO) in 3‐(nitrato‐κO)‐3,3‐bis(triphenylphosphane‐κP)‐3‐rhoda‐1,2‐dicarba‐closo‐dodecaborane(11) dichloromethane 2.2‐solvate

In the title compound, [Rh(C₂H₁₁B₉)(NO₃)(C₁₈H₁₅P)₂]·2.2CH₂Cl₂, studied as a 2.2‐solvate of what was assumed to be dichloromethane, the nitrate ligand lies cis with respect to both cage C atoms. Accordingly, the compound displays a pronounced preferred exopolyhedral ligand orientation (ELO) which is traced to both the greater trans influence of the cage B over the cage C atoms and the greater trans influence of the triphenylphosphane ligands over the nitrate ligand. The overall molecular architecture therefore agrees with that of a number of similar 3‐L‐3,3‐L′₂‐3,1,2‐closo‐MC₂B₉H₁₁ species in the literature.     

Mechanistic studies on the chiral recognition of polysaccharide-based chiral stationary phases using liquid chromatography and vibrational circular dichroism: Reversal of elution order of N-substituted alpha-methyl phenylalanine esters

Enantiomeric separation of two aromatic α-substituted alanine esters was achieved on two commercially available polysaccharide-based chiral stationary phases (CSPs): amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) and cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC). The interactions between enantiomeric analytes and the CSPs were investigated using chromatographic methods and vibration circular dichroism (VCD). The two analytes differ on the aromatic portion of the molecules where one analyte has a π-acceptor aromatic ring (1) while the other has a π-donor aromatic ring (2). When an ADMPC CSP was employed, an increase in the polarity of the mobile phase leads to a reversal of the elution order for the two enantiomers of 1. The elution order of compound 2 was not affected by the polarity of the mobile phase. In order to gain an understanding of these phenomena, the enantiomeric separation of 1 and 2 was also performed on the CDMPC CSP. Interestingly, no reversal of elution order was observed upon the chromatographic separation of both pairs of enantiomers of compounds 1 and 2 upon increasing the solvent polarity when a CDMPC CSP was utilized. To understand the underlying mechanism governing these chiral separations, VCD was applied to study the structure of the ADMPC and CDMPC polymers and their conformational behaviors under chromatographic conditions. For the first time the conformations of the side chains of both polymers were revealed based on the VCD spectra along with DFT calculations. Furthermore, the interactions between the two analytes and the two CSPs were directly probed by VCD. By comparing the spectral differences of the two CSPs in the presence of the two analytes, the detailed interactions involving different functional groups associated with the chiral recognition were elucidated and thus explained the unusual reversal of elution order associated with increasing solvent polarity.