Total synthesis of gelsemoxonine

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Natural Product Synthesis

Background:

• Gelsemoxonine is a complex natural product with a unique spiro-quaternary carbon center and a bicyclic seven-membered core.
• The total synthesis of such intricate molecules presents significant challenges in stereochemical control and structural assembly.

Purpose of the Study:

• To achieve the first total synthesis of gelsemoxonine.
• To develop and apply novel synthetic methodologies for constructing complex molecular architectures.

Main Methods:

• Utilized a divinylcyclopropane-cycloheptadiene rearrangement to establish the spiro-quaternary center and bicyclic core.
• Employed a one-pot isomerization of an α,β-unsaturated aldehyde to a saturated ester using TMSCN-DBU.
• Achieved diastereoselective introduction of the nitrogen functionality for the azetidine ring.

Main Results:

• Successfully completed the first total synthesis of gelsemoxonine.
• Demonstrated the efficacy of the divinylcyclopropane-cycloheptadiene rearrangement in assembling the target's core structure.
• Established a facile method for the stereoselective incorporation of the azetidine moiety.

Conclusions:

• The developed synthetic route provides a viable pathway to gelsemoxonine.
• The study highlights the utility of the employed rearrangement and isomerization reactions in complex molecule synthesis.
• This work expands the synthetic chemist's toolkit for accessing challenging natural product scaffolds.