13C-NMR Spectra of Strychnos Alkaloids: Brucine and Strychnine

The 1H and 13C NMR chemical shifts of Strychnos alkaloids revisited at the DFT level

“…It is seen in Figure 2 that the MAE of calculated 1 H NMR chemical shifts is only 0.08 ppm in the range of about 7 ppm (almost the same as the accuracy of the routine experimental measurements) and only 1.67 ppm for 13 C NMR chemical shifts in the range of about 150 ppm, so that the mean absolute percentage error is as small as~1% in both cases. This is exemplified with 4-hydroxystrychnine (4) providing a MAE of only 1.35 ppm for 21 13 C NMR chemical shifts of compound 4 as shown in Figure 3. The results for the parent strychnine are even better, and this is discussed in more detail in our previous publication.…”

“…Indeed, the Strychnos alkaloids, the vitally important natural products, attract an unflagging attention of theoretical chemists dealing with the calculation of their nuclear magnetic resonance (NMR) chemical shifts and spin-spin coupling constants, as exemplified by the most representative recent studies [1][2][3][4][5][6][7] together with earlier salient results. [8][9][10][11][12][13][14][15][16][17][18] In view of the large molecular size, severe proton deficiency, strong intramolecular stereoelectronic effects, and characteristic of Strychnos alkaloids, such as calculations, require a substantial computational effort and present a challenging task for modern computational NMR. [19][20][21][22][23][24][25][26][27][28][29][30] In this respect, calculation of 1 H and 13 C NMR chemical shifts of Strychnos alkaloids is of the utmost importance in view of their prospective application to chemical identification, spectral assignment, and structural elucidation of biochemical pathways.…”

“…It is well known that combination of the advanced experimental NMR techniques with the modern computational facilities provides a powerful tool for the structural elucidation of natural products and biosynthetic molecules, establishing absolute configuration and evaluating the mechanisms of their formation in vivo. Advances of computational 1 H and 13 C NMR of natural products are very well-documented in hundreds of the original publications by a number of principal authors including (listed alphabetically) Alvarenga, Bifulco, Buevich and Martin, Cen-Pacheko, Kutateladze, Saielli and Bagno, Sarotti, Tantillo, and many others. Herewith, we do not give references on the numerous publications in this area, forwarding the reader to a couple of most recent comprehensive reviews on this topic.…”

“…On the basis of this result, it was concluded by the authors that "it is, therefore, apparent that the statistical quality of the fit, while providing a broad assessment of the performance, may not be a trustworthy indicator of the usefulness of a given set of calculations." [41] In this paper, we report on the calculation of 1 H and 13 C NMR chemical shifts in the series of 10 most representative Strychnos alkaloids 1-10 shown in Figure 1, using the most effective DFT computational scheme, PBE0/pcSseg-2//pcseg-2, derived in our antecedent study of parent strychnine (1). [42] 2 | COMPUTATIONAL DETAILS Geometry optimization of the studied series of strychnines 1-10 was performed with GAUSSIAN 09 [43] code at the B3LYP/aug-cc-pVQZ level, taking into account solvent effects of chloroform within the integral equation formalism polarizable continuum model.…”

“…[52,53] To convert calculated 1 H and 13 C isotropic shielding constants (σ) to 1 H and 13 C NMR chemical shifts (δ), the linear regression analysis has been carried out, as described, for example, by Navarro-Vázquez, [54] Mulder and Filatov, [26] and Forsyth and Sebag. [55] The recommended linear scaling parameters, as well as computational efficiency and Root Mean Square (RMS) deviations for different levels of theory, are reviewed by Lodewyk, et al [56] FIGURE 2 Correlation plots of chemical shifts in the studied series of Strychnos alkaloids calculated using the PBE0/pcSseg-2//pcseg-2 locally dense basis set scheme versus experiment: (a) 1 H NMR chemical shifts; (b) 13 C NMR chemical shifts. MAE, mean absolute error Enumeration of protons is given in Figure 1.…”