Hidden Flexibility of Strychnine

Abstract

H and 13 C NMR spectra were recorded on a Bruker DRX 500 instrument (BBO probe) at 500.13 and 125.76 MHz, respectively, in steps of 10 K between 210 and 280 K (15 mg of the base form in 600 L CDCl 3 ), between 180 and 280 K (10 mg of the hydrochloride in 600 L [d4]methanol), and 298 K. Temperature calibration was done with a methanol reference sample. 1 H NMR spectra were acquired using a spectral width of 12 kHz, an acquisition time of 5.5 s and 16 scans, zerofilled to 128 k datapoints (0.09 Hz per point) and processed with a 1 Hz exponential decay. 13 C NMR spectra were acquired using a spectral width of 30 kHz, an acquisition time of 1.1 s and 2048 scans in about 1h, zerofilled to 128 k datapoints (0.23 Hz per point) and also processed without apodization. Peaks were fitted to a Lorentzian lineshape using MestreNova 8.0.0 (MestreLab Research S.L.) To increase the signal-to-noise ratio for peaks broadened beyond 20 Hz, the 13 C NMR spectra were reprocessed with a 5 Hz exponential decay. 1 H-EXSY spectra were recorded on a TBI inverse probe at 210 K (both samples), 200 and 190 K (hydrochloride in methanol-d 4 ). The spectra were acquired using a spectral width of 4 kHz, 1024 x 512 complex time domain datapoints, a mixing period of 50 ms (additionally 200 ms at 190 K) and 8 scans in about 4.5 h. The spectra were zerofilled to 2048 x 2048 datapoints and processed with a shifted square sine bell apodization in both dimensions. Populations and exchange rates were obtained from diagonal-and crosspeak integrals using EXSYCalc (MestreLab Research S.L.).

Stereochemical analysis of (+)-limonene using theoretical and experimental NMR and chiroptical data

“…In addition, previous work on a minor conformer of strychnine indicated that the mpw1pw91/cc-pvdz level of theory is superior to the "working horse" of geometry optimization, i.e. B3LYP/6-31G(d) [17].…”

“…The latter point is also related to the accuracy with which the rotational strengths are calculated. Based on own results [17,60], we can assume differences of a factor of two between calculation and experiment concerning the rotational and dipolar strengths.…”

“…Based on the results for strychnine base and the protonated/HCl form [17,18], we further explore the success and limitations of the absolute configuration (AC) determination using a comparison of experimental and calculated chiroptical data. Two recent publications nicely illustrate the importance of solvent modelling for the interpretation of chiroptical data [19a].…”

Stereochemical analysis of menthol and menthylamine isomers using calculated and experimental optical rotation data

“…A detailed study of limonene has shown that the mpw1pw91/ccpvdz level of theory delivers reliable results for the calculation of 13 C chemical shifts [29]. In addition, this level of theory was successful in the geometry optimization of a low-populated conformer of strychnine, base and HCl [30,31].…”

Evaluating the accuracy of theoretical one‐bond 13C─13C scalar couplings and their ability to predict structure in a natural product

“…A wide variety of structural factors can influence the magnitude of 1 J CC . For example, prior work has demonstrated that the 1 J CC coupling is sensitive to dihedral angle, where changes as large as 9 Hz between different conformations have been reported. Stereochemical configuration also influences 1 J CC coupling, where, for example, the 1 J CC coupling in methyl α‐D‐mannopyranoside differs from the β‐D‐mannopyranoside by 4 Hz .…”