WR abstract
Structure elucidation of organic natural products is a complex task mainly performed using spectroscopic methods. Among the techniques applied, NMR-spectroscopy plays a central role giving a detailed insight into constitution, configuration and conformation of the unknown compound. Despite the tremendous progress made in tailoring sophisticated pulse techniques to solve structural problems, many natural products have been published showing a wrong structure proposal leading to incorrect reference material for subsequent conclusions with the effect of making this erroneous knowledge base statistically more significant. A large number of comprehensive review articles [1,2] describes the actual situation in detail. From this analysis the necessity of massive software application during every step of the process of structure elucidation can be derived. The automatic peer-reviewing of some 700,000 C13-NMR spectra mainly taken from the public domain literature has revealed a significant number of wrong structure proposals and/or wrong signal assignments [3]. Subsequent application of a structure generator program based on the carbon-NMR data has created reasonable alternatives - in many cases in full agreement with an already known structure revision. Examples will be given showing the immediate need to change the workflow of structure elucidation along the line from spectrum interpretation to peer-reviewing of manuscripts [4,5,6].
[1] Nicolaou KC, Snyder SA. Chasing molecules that were never there: misassigned natural products and the role of chemical synthesis in modern structure elucidation. Angew Chem Int Ed 2005; 44:1012-1044
[2] McAlpine JB, Chen SN, Kutateladze A, MacMillan JB, Appendino G, Barison A, Beniddir MA, Biavatti MW, Bluml S, Boufridi A, Butler MS, Capon RJ, Choi YH, Coppage D, Crews P, Crimmins MT, Csete M, Dewapriya P, Egan JM, Garson MJ, Genta-Jouve G, Gerwick WH, Gross H, Harper MK, Hermanto P, Hook JM, Hunter L, Jeannerat D, Ji NY, Johnson TA, Kingston DGI, Koshino H, Lee HW, Lewin G, Li J, Linington RG, Liu M, McPhail KL, Molinski TF, Moore BS, Nam JW, Neupane RP, Niemitz M, Nuzillard JM, Oberlies NH, Ocampos FMM, Pan G, Quinn RJ, Reddy DS, Renault JH, Rivera-Chávez J, Robien W, Saunders CM, Schmidt TJ, Seger C, Shen B, Steinbeck C, Stuppner H, Sturm S, Taglialatela-Scafati O, Tantillo DJ, Verpoorte R, Wang BG, Williams CM, Williams PG, Wist J, Yue JM, Zhang C, Xu Z, Simmler C, Lankin DC, Bisson J, Pauli GF. The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research. Nat Prod Rep 2019; 36:35-107
[3] Robien W. A Critical Evaluation of the Quality of Published 13C NMR Data in Natural Product Chemistry Progress in the Chemistry of Organic Natural Products, eds. Kinghorn AD, Falk H, Gibbons S, Kobayashi JI 2017; 105:137-215
[4] Robien W. Computer-assisted peer reviewing of spectral data: The CSEARCH protocol. Monatsh Chem 2019; 150, 927-932 https://doi.org/10.1007/s00706-019-02407-5
