The Assignment of Absolute Stereostructures through Quantum Chemical Circular Dichroism Calculations

Abstract

The determination of the absolute configuration of a chiral compound of synthetic or natural origin is a problem that every organic chemist willl certainly have to face some day. An efficient and reliable method for the assignment of absolute stereostructures, independent of empirical CD rules, is the combination of experimental circular dichroism (CD) investigations with quantum chemical CD calculations. The availability of a broad variety of quantum chemical methods and the continuing appearance of new approaches permits -but also requires -the most appropriate method to be selected in each particular case, with respect to accuracy, time con-

A twist of nature – the significance of atropisomers in biological systems

“…However, to determine which spectrum corresponds to a particular configuration requires further analysis; often extensive 2D NMR techniques, however computational prediction is more routine. There are various ab initio methods which may be applied, 15 though the most common of these relies on optimizing the structures of the two predicted atropenantiomers with a density functional theory (DFT), then applying a time-dependent (TD) perturbation to predict the vibrational or electronic transitions. 16 Thus, the TD-DFT method calculates CD spectra, which may be compared to experimental spectra to confidently assign the relative atropisomerism.…”

“…Additionally, phenotypic analysis of cells treated with 12, 14, and 16 showed elongated rod-like cells; an indicator for the induction of the bacterial SOS pathway in response to DNA interference. However, due to the fact that all compounds (11)(12)(13)(14)(15)(16) showed a reduction in B. subtilis growth, it was assumed that this was just one pathway through which inhibition occurred, and was reliant on the absolute configuration of the atropdiastereomers. This is promising as it evidences variable activity of therapeutic compounds based on their atropisomeric configuration, however the group concluded it is likely the natural products may have an additional, potentially novel, mode of action though this requires further investigation.…”

Terretonin, ophiobolin, and drimaneterpenes with absolute configurations from an algicolous Aspergillus ustus

“…The total EtOAc-soluble fraction (35.5 g) was subjected to stepgradient silica gel column chromatography (CC) with a solvent system consisting of 0-100% petroleum ether (PE)-EtOAc to afford 14 fractions (Frs. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] on the basis of TLC analysis. Fr.…”

Two halosesquiterpenes from Laurencia composita

“…3) using the timedependent density function theory (TD-DFT) method at the B3LYP/6-31G(d) level. [12][13][14] Thus, an absolute configuration of 2S, 3S, 5S, 6R, 7R, and 10R was assigned to both 1 and 2. It was interesting that the experimental ECD spectrum of 2 exhibited a redshift (ca.…”