Structural and chiroptical analysis of naturally occurring (–)-strychnine

Abstract

Structural aspects such as chemical exchange, dimerization, solvent association, nitrogen inversion and protonation status of strychnine were investigated using experimental and calculated data. The information was mainly interpreted in view of a successful determination of the absolute configuration (AC) with strychnine (base and salt) as test molecule due to its importance in chemistry. By geometry optimization a stable isomer of protonated strychnine was found with an inverted nitrogen, however, 25 kcal/mol higher in energy. It is shown that solvent association can be assumed in protic solvents such as methanol and dimerization to a small extent in polar/protic solvents. However, the monomeric structural model neglecting explicit solvent molecules still allows the correct prediction of the AC of base and hydrochloride using optical rotation and ECD data.

Engineering a surrogate human heteromeric α/β glycine receptor orthosteric site exploiting the structural homology and stability of acetylcholine-binding protein

“…In both of these structures the molecular packing in the crystal lattice affects the conformation of loop C in one subunit and results in a more open binding site, providing room for ligands to adopt different orientations. We note also that this alkaloid displays a propensity to dimerize or aggregate at high concentrations (Reinscheid et al, 2016). Our structure of the WT AcAChBPstrychnine complex displays a single well ordered strychnine in all five binding sites per asymmetric unit and we confine our comparison to this binding pose (Fig.…”

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

“…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].…”