np9b00603_si_002.xlsx (1.19 MB)
Efficient Protocol for Accurately Calculating 13C Chemical Shifts of Conformationally Flexible Natural Products: Scope, Assessment, and Limitations
datasetposted on 2019-07-19, 16:08 authored by Warren Hehre, Phillip Klunzinger, Bernard Deppmeier, Andy Driessen, Noritaka Uchida, Masaru Hashimoto, Eri Fukushi, Yusuke Takata
An efficient protocol for calculating 13C NMR chemical shifts for natural products with multiple degrees of conformational freedom is described. This involves a multistep procedure starting from molecular mechanics and ending with a large basis set density functional model to obtain accurate Boltzmann conformer weights, followed by empirically corrected density functional NMR calculations for the individual conformers. The accuracy of the protocol (average rms <4 ppm) was determined by application to ∼925 diverse natural products, the structures of which have been confirmed either by X-ray crystallography or independent synthesis. The protocol was then applied to ∼ 2275 natural products, the structures of which were elucidated mainly by NMR and MS data. Five to ten percent of the latter compounds exhibited rms errors significantly in excess of 4 ppm, suggesting possible structural or signal assignment errors. Both data sets are available from an online browser (NMR.wavefun.com). The procedure can be and has been fully automated and is practical using present-generation personal computers, requiring a few hours or days depending on the size of the molecule and number of accessible conformers.