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

• An isomer of protonated strychnine was identified with an inverted nitrogen.
• Solvent association of strychnine can be assumed in protic solvents.
• Dimerization might occur to a small extent in polar/protic solvents.
• A correct prediction of the absolute configuration is based on ORD and ECD data.

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.

A detailed analysis of experimental and calculated data approved a monomeric structural model of strychnine (base and protonated/HCl) which could successfully be used for the assignment of the absolute configuration on the basis of chiroptical data (ORD, ECD, VCD). A number of dynamic processes such as solvent-solute association and nitrogen inversion/protonation could be idenfified.Figure optionsDownload as PowerPoint slide