Chiroptical studies on brevianamide B: vibrational and electronic circular dichroism confronted.

Chiroptical spectroscopies, such as electronic circular dichroism (ECD) and vibrational circular dichroism (VCD), are highly sensitive techniques to probe molecular conformation, configuration, solvation, and aggregation. Here we report the application of these techniques to study the fungal metabolite brevianamide B. Comparison of the experimental ECD and VCD spectra with the density functional theory simulated counterparts establishes that VCD is the more reliable technique to assign absolute configuration due to the larger functional and dispersion dependence of computed ECD spectra. Despite a low amount of available material and a relatively unusual example of using VCD carbonyl multiplets, the absolute configuration could be reliably predicted, strengthening the case for application of VCD in the study of complex natural products. Spectral and crystallographic evidence for or against the formation of a dimeric aggregate is discussed; in solution, the VCD spectra strongly suggest only monomeric species are present.

Mechanistic and chiroptical studies on the desulfurization of epidithiodioxopiperazines reveal universal retention of configuration at the bridgehead carbon atoms.

The stereochemistry of the desulfurization products of chiral natural and synthetic 3,6-epidithiodiketopiperazines (ETPs) is specified inconsistently in the literature. Qualitative mechanisms have been put forward to explain apparently divergent stereochemical pathways, but the quantitative feasibility of such mechanistic pathways has not been assessed. We report a computational study revealing that desulfurization of ETPs should occur universally with retention of configuration. While the majority of stereochemically assigned and reassigned cases fit this model, until now desulfurization of the synthetic gliotoxin analogue shown has remained assigned as proceeding via inversion of configuration. Through detailed chiroptical studies comparing experimentally obtained optical rotation values, electronic circular dichroism spectra, and vibrational circular dichroism spectra to their computationally simulated counterparts as well as chemical derivatization studies, we have unambiguously demonstrated that contrary to its current assignment in the literature, the desulfurization of this synthetic ETP also proceeds with retention of configuration.

On the determination of the stereochemistry of semisynthetic natural product analogues using chiroptical spectroscopy: desulfurization of epidithiodioxopiperazine fungal metabolites.

Isolation and semisynthetic modification of the fungal metabolite chaetocin gave access to a desulfurized analogue of this natural product. Detailed chiroptical studies, comparing experimentally obtained optical rotation values, electronic circular dichroism spectra, and vibrational circular dichroism spectra to computationally simulated ones, reveal the desulfurization of chaetocin to unambiguously proceed with retention of configuration. Consideration of the plausible mechanisms for this process highlighted inconsistencies in the stereochemical assignment of related molecules in the literature. This in turn allowed the stereochemical reassignment of the natural product analogue dethiodehydrogliotoxin.