Concise Total Synthesis of Ivorenolide B

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Ivorenolide B is a potential immunosuppressive lead compound.
• Synthesizing complex macrocycles containing 1,3-diyne units presents significant challenges.
• Previous alkyne metathesis methods were incompatible with sensitive functional groups.

Purpose of the Study:

• To develop an efficient synthetic route to ivorenolide B.
• To demonstrate the utility of a novel molybdenum catalyst for ring-closing alkyne metathesis (RCAM).
• To showcase the compatibility of RCAM with acid-sensitive propargylic alcohols and terminal alkynes.

Main Methods:

• Ring-closing alkyne metathesis (RCAM) using a molybdenum alkylidyne complex (catalyst 7).
• Synthesis of a 17-membered cyclization precursor containing a 1,3-diyne subunit.
• Post-metathetic transformations using gold or palladium catalysts.

Main Results:

• Successful synthesis of the 1,3-diyne subunit within the 17-membered framework of ivorenolide B.
• The molybdenum catalyst demonstrated compatibility with acid-sensitive propargylic alcohol substituents and terminal alkynes.
• Post-metathetic functionalization of cyclo-1,3-diynes yielded various cyclophane products.

Conclusions:

• The developed RCAM strategy provides an expeditious route to ivorenolide B.
• The novel molybdenum catalyst significantly expands the scope and applicability of alkyne metathesis.
• This work highlights the potential for further structural diversification of macrocyclic compounds through advanced catalytic methods.