The distorted tropane of scopoline.

Area of Science:

• Physical Chemistry
• Molecular Spectroscopy
• Organic Chemistry

Background:

• Scopine and scopoline (oscine) are tropane alkaloids with potential pharmaceutical applications.
• Understanding their gas-phase structures is crucial for elucidating their properties and reactivity.
• Previous studies have lacked detailed structural information in the gas phase.

Purpose of the Study:

• To investigate the structural isomerization of scopine to scopoline in the gas phase.
• To characterize the molecular structure of scopoline using microwave spectroscopy.
• To provide a detailed description of the tropane framework in scopoline.

Main Methods:

• Microwave spectroscopy was employed to study the molecular structure in a supersonic jet expansion.
• Rotational spectra were analyzed to determine the structure of the gas-phase species.
• Ab initio (MP2) and DFT (B3LYP, M06-2X) calculations were used for theoretical support.

Main Results:

• Evidence of structural isomerization from scopine to scopoline was observed.
• A single, structurally distorted tropane structure was identified for scopoline in the gas phase.
• The isomerization was found to be nearly quantitative at experimental vaporization temperatures (ca. 90°C).

Conclusions:

• The intramolecular cyclization of scopine forms scopoline, breaking the epoxy group and creating an ether bridge.
• Scopoline adopts a 7β-hydroxytropane configuration stabilized by an intramolecular O-H⋅⋅⋅N hydrogen bond.
• This hydrogen bond influences the conformation of the N-methyl group, favoring the axial form.