Computational NMR of natural products: On the way to super large molecules exemplified with alasmontamine A

Abstract

H and 13 C nuclear magnetic resonance (NMR) chemical shifts of a tetrakis monoterpene indole alkaloid alasmontamine A with a molecular formula of C 84 H 91 N 8 O 12 have been calculated at the PBE0/pcSseg-2//pcseg-2 level of theory on M06-2X/aug-cc-pVDZ geometry. In the course of the preliminary conformational search, six true minimum energy conformers were identified that can contribute to the actual conformation of this huge alkaloid. Calculated chemical shifts generally demonstrated a good agreement with available experimental data characterized with a corrected mean absolute error of 0.10 ppm for the range of about 7 ppm for protons and 1.1 ppm for the range of about 160 ppm for carbons.

Analytical and Structural Tools of Lipid Hydroperoxides: Present State and Future Perspectives

“…Quantum chemical calculations of NMR parameters have also been extensively used for the precise determination of diastereomerism of natural products with multiple asymmetric centers [ 138 , 141 , 142 , 143 , 158 , 159 , 160 , 161 ]. On the contrary, in the field of lipid hydroperoxides, only three papers have so far been reported [ 138 , 141 , 156 ].…”

Computational1H and13C NMR in structural and stereochemical studies

“…The equilibrium structure of alasmontamine A was later optimized at the M06-2X/aug-cc-pVDZ level (diffused functions were used only on N and O atoms possessing multiple lone pairs), while calculation of 1 H and 13 C NMR chemical shifts was carried out using the PBE0 functional with the pcSseg-2 basis set for H and C atoms and pcseg-2 on N and O atoms. [361] It was found that calculated 1 H and 13 C NMR chemical shifts provided good correlation with their experimental values, as illustrated in Figure 35. The only marked deviation between calculated and experimental 13 C NMR chemical shifts were reported for C-3 00 and C-23 000 which possibly points to the need for their reassignment.…”

“…For the sake of better visualability, hydrogen atoms are not shown in the molecular structure; for details, see paper by Semenov and Krivdin. [361] 79…”

“…Reproduced from Hirasawa, et al [360] with the permission of the American Chemical Society S C H E M E 1 3 Plausible biogenetic path for alasmontamine A. Reproduced from Hirasawa, et al [360] with the permission of the American Chemical Society F I G U R E 3 5 Calculated versus experimental 1 H and 13 C NMR chemical shifts (left and right, respectively) of alasmontamine. Reproduced from Semenov and Krivdin [361] with the permission of John Wiley and Sons…”

Stereochemical Study of the Super Large Tetrakis Alkaloid Alasmontamine A by Means of an Advanced Computational NMR

“…The 2D chemical structure of this large alkaloid providing the enumeration of atoms (with omitting hydrogens for clarity) is provided below, while its 3D structure is presented in Figure 1 . A preliminary communication dealing with the conformational study of this compound was published in Magnetic Resonance in Chemistry [ 10 ].…”