Efficient synthesis of (±)-de-O-methyllasiodiplodin

Area of Science:

• Natural Product Synthesis
• Organic Chemistry
• Fungal Metabolites

Background:

• Resorcinolic macrolides are fungal natural products characterized by a resorcinolic ester core and variable macrocycles.
• Their biological activities are significantly influenced by macrocycle size and substitutions.
• Understanding and synthesizing these compounds is crucial for exploring their therapeutic potential.

Purpose of the Study:

• To develop a protecting group-free synthetic route for a minimal resorcinolic macrolide, (±)-de-O-methyllasiodiplodin.
• To establish an efficient method for generating diverse libraries of resorcinolic macrolides.

Main Methods:

• A 5-step synthesis starting from readily available 9-decenoic acid.
• Utilized a protecting group-free strategy to streamline the synthesis.
• Achieved a 42% overall yield for the target compound.

Main Results:

• Successfully synthesized (±)-de-O-methyllasiodiplodin.
• Demonstrated an efficient and scalable synthetic route.
• The methodology allows for facile modification of the macrocycle bridge.

Conclusions:

• The developed synthetic route offers a valuable platform for accessing diverse resorcinolic macrolide analogs.
• This approach facilitates the exploration of structure-activity relationships for this important class of natural products.
• Enables the generation of compound libraries for drug discovery and development.