Synthesis and structure elucidation of a series of pyranochromene chalcones and flavanones using 1D and 2D NMR spectroscopy and X-ray crystallography Sunayna S. Pawar and Neil A. Koorbanally* A series of novel pyranochromene chalcones and corresponding flavanones were synthesized. This is the first report on the confirmation of the absolute configuration of chromene-based flavanones using X-ray crystallography. These compounds were characterized by 2D NMR spectroscopy, and their assignments are reported herein. The 3D structure of the chalcone 3b and flavanone 4g was determined by X-ray crystallography, and the structure of the flavanone was confirmed to be in the S configuration at C-2. Copyright © 2014 John Wiley & Sons, Ltd. Keywords: NMR; 1 H; 13 C; X-ray crystallography; pyranochromene; chalcones; flavanones Introduction Chalcones and flavanones form a large and important group of naturally occurring secondary metabolites. [1] Chalcones are im- portant intermediates for the synthesis of biologically active com- pounds such as flavone, flavonol, flavanone, isoflavone and their derivatives. [2] Besides having a physiological role in plants, flavo- noids have also been reported to have a wide variety of biologi- cal activities, including anti-inflammatory, antiviral, antiprotozoal, antioxidant, cardiovascular and anticarcinogenic properties. [2] A five-membered prenyl moiety on a benzene ring cyclized with an oxygen atom on an adjacent position leads to a benzopyran or chromene molecule with a second such cycliza- tion leading to a pyranochromene such as the naturally occurring octandrenolone, [3,4] O-methyloctandrenolone, [4,5] trans-3‴,4‴- dihydro-3‴,4‴-dihydroxy-O-methyloctandrenolone, [4] trans-3″,4″- dihydro-3″,4″-dihydroxy-O-methyloctandrenolone, [4] flemiculosin, [6] laxichalcone, [7] 3-deoxy-MS-II [3,8,9] and MS-II. [3,8] The flavanone (4a) 3-deoxy–MS-II (Scheme 1), which incorporates pyranochromene moieties, was isolated from the methanolic extracts of the bark and leaf of Mundulea chapelieri and exhibited activity against a human ovarian cancer cell line. [8] Shortly afterward, its synthesis was reported. [3] The synthesis of six chalcones with an octandrenolone moiety was also reported. [10] Several other pyranochromene chalcones and flavonoids were isolated from Mundulea suberosa and Mundulea sericea and have exhibited interesting biological activities including antimicrobial and ornithine decarboxylase activity. [8,11–17] A pyranochromene chalcone, (-)-rubranine with prenyl groups on the pyran rings, was also isolated from Aniba rosaeodora. [18] Two series of prenylated chromenochalcones were also synthesized and tested for their antileishmanial and antimalar- ial activity where several compounds showed good activity. [19,20] In our ongoing study on synthesizing fluorinated pharmaceuti- cals, we have prepared several fluorinated chalcones and flavanones with the pyranochromene moiety. Herein, we report the NMR elucidation of these fluorinated pyranochromene chalcones and flavanones, which is slightly more complicated than the oxygenated or chlorinated molecules because of the fluorine atom being NMR active and coupling with both hydrogen and carbon. We used X-ray crystallography and NMR studies to provide a full structural elucidation of these novel pyranochromene chalcones and flavanones. Experimental Reagents and chemicals used in this study were purchased from Sigma-Aldrich via Capital Lab, South Africa and were reagent grade. All organic solvents were redistilled and dried according to standard procedures. Optical rotations were recorded using a PerkinElmer™ Model 341 Polarimeter with a 10-cm flow tube. Melting points were measured using a Stuart scientific melting point apparatus SMP3. IR spectra were recorded on a PerkinElmer Spectrum 100 FT-IR spectrometer with universal attenuated total reflectance sampling accessory. UV spectra were obtained on a Varian Cary UV-VIS spectrophotometer in chloroform. High- resolution mass data were obtained using a Bruker microTOF-Q II ESI instrument operating at ambient temperatures, with a sample concentration of approximately 1 ppm. Thin-layer chroma- tography was performed using Merck Kieselgel 60F 254 plates. Crude compounds were purified with column chromatography using silica gel (60–120 mesh) as the stationary phase and varying combinations of solvents depending on the sample to be purified. * Correspondence to: Neil A. Koorbanally, School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa. E-mail: Koorbanally@ukzn.ac.za; Neil.Koorbanally@gmail.com School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa Magn. Reson. Chem. 2014, 52, 279–288 Copyright © 2014 John Wiley & Sons, Ltd. Research article Received: 24 October 2013 Revised: 21 February 2014 Accepted: 24 February 2014 Published online in Wiley Online Library: 13 March 2014 (wileyonlinelibrary.com) DOI 10.1002/mrc.4062 279