Structure of 18'-epivinblastine

Area of Science:

• Organic Chemistry
• Crystallography
• Medicinal Chemistry

Background:

• Complex indole alkaloids, such as those derived from vindoline and catharanthine, are significant in medicinal chemistry.
• Understanding the precise three-dimensional structure of these molecules is crucial for elucidating their biological activity and for synthetic efforts.

Purpose of the Study:

• To determine the detailed crystal structure of a novel methyl ester derivative of an indole alkaloid solvated with methanol.
• To characterize the molecular conformation, including ring structures and stereochemistry.
• To identify and analyze intramolecular hydrogen bonding interactions within the molecule.

Main Methods:

• Single-crystal X-ray diffraction analysis was performed on the title compound (C46H58N4O9. 2CH3OH).
• The crystal structure was solved and refined using Mo K alpha radiation at 198 K.
• Conformational analysis of the various ring systems (C, D, E rings, piperidine, and azacyclononene rings) was conducted.

Main Results:

• The crystal structure of the title compound was successfully determined, with a final R-factor of 0.0470.
• The C ring of the vindoline moiety adopts a boat conformation, featuring an intramolecular hydrogen bond (O3--H3...N9).
• The catharanthine portion's piperidine ring is in a chair conformation, and its azacyclononene ring is in a boat-chair conformation, with another intramolecular hydrogen bond (N16'--H16'...O25) observed.

Conclusions:

• The study provides a precise structural elucidation of a complex indole alkaloid derivative.
• The identified intramolecular hydrogen bonds likely play a significant role in stabilizing the observed molecular conformations.
• This detailed structural information is valuable for future research in synthetic chemistry and drug discovery involving similar alkaloid scaffolds.