Synthesis of (+)-obtusenyne

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Heterocyclic Chemistry

Background:

• Medium-ring oxygen heterocycles are prevalent in natural products.
• The synthesis of complex halogenated ethers like (+)-obtusenyne presents significant challenges.

Purpose of the Study:

• To develop an enantioselective synthesis of the natural product (+)-obtusenyne.
• To explore the chemistry of medium-ring oxygen heterocycles.

Main Methods:

• Ring expansion of a seven-membered ketene acetal via Claisen rearrangement to form the nine-membered oxygen heterocycle.
• Transition-metal-catalyzed intramolecular hydrosilation of an exo-cyclic enol ether to establish trans substituents.
• Formal synthesis of ent-obtusenyne from 2-deoxy-D-ribose.

Main Results:

• Successful enantioselective synthesis of (+)-obtusenyne.
• Stereoselective installation of trans substituents across the ether linkage.
• Demonstration of a formal synthesis from a readily available carbohydrate precursor.

Conclusions:

• The developed synthetic strategy provides efficient access to halogenated medium-ring ether natural products.
• The study highlights key chemical transformations relevant to medium-ring oxygen heterocycles.
• The findings contribute to the broader field of natural product synthesis and methodology development.