Vibrational Circular Dichroism Absolute Configuration of Natural Products From 2015 to 2019

Abstract

Although demonstrated in 1975, vibrational circular dichroism (VCD) finally started to popularize during this century as a reliable tool to determine the absolute configuration (AC) of organic molecules. This research field continues to be a very dynamic one, in particular for the study of natural products which are a unlimited source of chiral molecules. It therefore turns of interest to summarize the accomplishments published in recent years and to comment on some eventual difficulties that emerged in rare cases to complete the AC determination task. Therefore the aim of this review is to update VCD results for the AC assignment of natural products published from 2015 to 2019, a period in which VCD was reported in some 126 publications involving almost 300 molecules. They are organized according the type of studied metabolite allowing an easily search. The molecules correspond to 28 monoterpenes concerning 17 papers, to 42 sesquiterpenes in 14 papers, to 51 diterpenes in 19 publications, to 5 other terpenoids in three papers, to 48 aromatic molecules in 15 reports, to 20 polyketides in 10 publications, to 27 miscellaneous formulas also in 10 papers, and to 76 nitrogen containing compounds, which include alkaloids and their synthetic analogs, in 38 articles. The landscape of reviewed molecules is quite wide as it goes from simple monoterpenes, like borneol or camphor, to very relevant biological molecules like the alkaloid cocaine or tadalafil samples to distinguish genuine and counterfeit Cialis®. In addition, 5 natural products and a simple derivative published outside the reviewed period, were used to illustrate some aspects of density functional theory calculations.

Absolute configuration assignment of stigmasterol oxiranes

“…Two NMR criteria for the C-22/C-23 AC assignment were already proposed. The first criterion 10 was based on a qualitative conformational analysis of a series of sterols, including 13 and 14, which considered the 13 C NMR chemical shift for C-22 and C-23 in the 22R,23R stereoisomers is very similar, showing a Δδ around 0.1 ppm. Whereas in the 22S,23S series this Δδ is around 4.6 ppm.…”

“…The most stable DFT B3LYP/DGDZVP conformers of (5R,6S,22S,23S)-diepoxystigmasteryl acetate ( 22) T A B L E 5 NMR data of 3, 12-14 (in CDCl 3 , 1 H 500 at MHz, 13 C 125 at MHz)…”

Vibrational Circular Dichroism Similarity-Guided Absolute Configuration Determination of 11-Acyloxytremetones

“…In addition, naturally occurring benzodihydrofurans 1 and 2 were successfully tested 4 as growth inhibitors of the insect species Tenebrio molitor, while the structure of 1 was independently verified 5 in a single-crystal x-ray diffraction (XRD) study. 5 From our three lustrous vibrational circular dichroism (VCD) experience, accumulated since the first study 6 of alkaloids from plants of Chilean origin, through the years during which a few VCD reviews 7,8 were put forward, 9 until current times, 10 it could be expected that the structural attributes of 1 would allow a straightforward AC determination of the molecule. Inspection of the structure of 1 reveals that this C 22 H 20 O 5 compound possesses only 4 sp 3 carbon atoms of which one is a methyl group, a sole stereogenic center which is located at C-2 on a benzodihydrofuran ring system and has an almost rigid p-hydroxycinnamoyl ester group whose phenolic hydroxy group can adopt 2 orientations.…”

Taxonomy-Focused Natural Product Databases for Carbon-13 NMR-Based Dereplication

“…Ambiguity from NMR arises often from the lack of configuration assignment to chiral structure elements, while planar structures are generally defined to a high level of accuracy [14]. While NMR spectra offer the possibility of distinguishing between diastereomers, even for compounds in mixtures, enantiomer identification requires either the isolation of pure compounds for their study by chiroptical methods or chemical derivatization by a homochiral reagent and subsequent NMR analysis [15,16].…”