REGULAR ARTICLE Revisiting empirical rules for the determination of the absolute configuration of cascarosides and other (ox‐) anthrones Daniel P. Demarque 1,2 | Danielle R. Pinho 2 | Norberto P. Lopes 2 | Christian Merten 1 1 Organic Chemistry 2, Physical Organic Chemistry, Ruhr‐University Bochum, Bochum, Germany 2 Núcleo de Pesquisa em Produtos Naturais e Sintéticos, Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil Correspondence Christian Merten, Organic Chemistry 2, Physical Organic Chemistry, Ruhr‐ University Bochum, Universitätsstraße 150, 44801 Bochum, Germany. Email: christian.merten@ruhr‐uni‐ bochum.de Abstract The introduction of the C 10 ‐stereocenter of (ox‐)anthrones by plant organisms is not stereospecific. Consequently, often, both (10S)‐ and (10R)‐diastereomers can be found in the same plant. Motivated by the importance of a correct assignment of the configuration at C 10 , this study revisits the nuclear magnetic resonance and electronic circular dichroism‐based empirical rules for the deter- mination of the absolute configuration by molecular dynamic simulations and electronic circular dichroism spectrum calculations. Furthermore, a vibrational circular dichroism spectroscopic characterization of these large and conformationally very flexible molecules reveals spectral signatures, which can be used to specifically distinguish the C 10 stereochemistry. A detailed anal- ysis of the underlying vibrational modes suggests that the observed spectral pat- tern of the investigated cascarosides may be generally characteristic for the C 10 ‐stereocenter of (ox‐)anthrones and that they can be used for empirical spec- tra‐structure correlations. KEYWORDS conformational analysis, hydrogen bonding, natural products, structure elucidation, vibrational circular dichroism 1 | INTRODUCTION Anthrone and oxanthrone are important anthraquinone derivatives found in many plants, which are nowadays used in pharmaceutical products as laxatives or for weight loss as well as in cosmetics. 1,2 To avoid diarrhea and dehy- dration, some of these plants need to be stored for at least a year to ensure the oxidation of anthrones to oxanthrones. 3 Hence, the ratio of anthrones and oxanthrones can be used as chemical markers for quality and safety of the plant material before preparation of herbal medicine products. One such example is cascaroside A (cf. Scheme 1), which is used as chemical marker for Rhamnus purshiana. 4 Due their importance for quality control, detailed structure elucidation of these compounds has been a concern among the natural prod- ucts chemists. The structural variations for these com- pounds introduced by Nature comprise the presence of sugar moieties, hydroxyl and alkoxyl groups attached to the aromatic rings, and different substituents in the side chains (R2 in Scheme 1). In addition, the stereochemical assignment of anthrone and oxanthrone compounds is particularly important, as the introduction of the C 10 ‐ stereocenter by the plant organism is not stereospecific, so that often both (10S) and (10R)‐diastereomers can be found in the same plant. 5,6 In light of the nonselectivity of the formation of the C 10 ‐stereocenter, the determination of the correct abso- lute configuration (AC) is a crucial part of the structure elucidation process of anthrones and oxanthrones. Received: 28 August 2017 Revised: 10 November 2017 Accepted: 20 November 2017 DOI: 10.1002/chir.22803 Chirality. 2018;1–7. © 2018 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/chir 1