Determining the Absolute Configuration of Two Marine Compounds Using Vibrational Chiroptical Spectroscopy

Abstract

Chiroptical techniques are increasingly employed for assigning the absolute configuration of chiral molecules through comparison of experimental spectra with theoretical predictions. For assignment of natural products, electronic chiroptical spectroscopies such as electronic circular dichroism (ECD) are routinely applied. However, the sensitivity of electronic spectral parameters to experimental conditions and the theoretical methods employed can lead to incorrect assignments. Vibrational chiroptical methods (vibrational circular dichroism, VCD, and Raman optical activity, ROA) provide more reliable assignments, although they, in particular ROA, have been little explored for assignments of natural products. In this study, the ECD, VCD, and ROA chiroptical spectroscopies are evaluated for the assignment of the absolute configuration of a highly flexible natural compound with two stereocenters and an asymmetrically substituted double bond, the marine antibiotic Synoxazolidinone A (SynOxA), recently isolated from the sub-Arctic ascidian Synoicum pulmonaria. Conformationally averaged nuclear magnetic resonance (NMR), ECD, Raman, ROA, infrared (IR) and VCD spectral parameters are computed for the eight possible stereoisomers of SynOxA and compared to experimental results. In contrast to previously reported results, the stereochemical assignment of SynOxA based on ECD spectral bands is found to be unreliable. On the other hand, ROA spectra allow for a reliable determination of the configuration at the double bond and the ring stereocenter. However, ROA is not able to resolve the chlorine-substituted stereogenic center on the guanidinium side chain of SynOxA. Application of the third chiroptical method, VCD, indicates unique spectral features for all eight SynOxA isomers in the theoretical spectra. Although the experimental VCD is weak and restricted by the limited amount of sample, it allows for a tentative assignment of the elusive chlorine-substituted stereocenter. VCD chiroptical analysis of a SynOxA derivative with three stereocenters, SynOxC, results in the same absolute configuration as for SynOxA. Despite the experimental challenges, the results convincingly prove that the assignment of absolute configuration based on vibrational chiroptical methods is more reliable than for ECD.

Secondary Metabolites from Polar Organisms

“…From the sub-Arctic ascidian Synoicum pulmonaria collected off the Norwegian coast, three new brominated guanidinium oxazolidinones were isolated, named synoxazolidinones A–C ( 215 – 217 ) (Figure 20) [141,142,143]. The backbone of the compounds contains a 4-oxazolidinone ring rarely seen in natural products.…”

DFT investigation on dihydrogen-bonded amine-borane complexes

“…Vibrational circular dichroism (VCD) spectra As a powerful method to probe the binding topology of DHB systems, VCD spectra have been utilized both for the determination of absolute configurations and for structural studies of a wide range of systems ranging from small molecules to polymers [40][41][42][43]. The VCD spectra of the monomer and dimer complexes are shown in Fig.…”

Determination of the Absolute Configuration of Natural Product Molecules Using Vibrational Circular Dichroism

“…The second example by Hopmann et al [65] presents an extensive chiroptical analysis of synoxazolidinone A (20), an antimicrobial oxazolidinone recently isolated from the sub-Arctic ascidian Synoicum pulmonaria. The ECD analysis provided only very limited information on the configuration of 20.…”