Synthetic studies on the mycolactone core.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Mycolactone polyketides are complex natural products with significant biological activity.
• Efficient synthesis of the macrolide core is crucial for further research and development.

Purpose of the Study:

• To develop and present two distinct synthetic approaches for constructing the mycolactone macrolide core.
• To provide reliable routes for accessing mycolactone derivatives for further investigation.

Main Methods:

• The first approach integrates ring closing metathesis (RCM) within a two-step Julia olefination sequence.
• The second approach utilizes and modifies optimized synthetic routes previously developed by Kishi.
• Both methods focus on the efficient construction of the macrolide scaffold.

Main Results:

• Successful synthesis of the macrolide core was achieved through both presented methodologies.
• The RCM-Julia olefination approach offers a convergent strategy for macrolide assembly.
• Interception of Kishi's routes provides an alternative and validated pathway.

Conclusions:

• Two viable and distinct synthetic routes to the mycolactone macrolide core have been established.
• These synthetic strategies enhance the accessibility of mycolactone polyketides for biological studies.
• The presented work contributes to the field of complex natural product synthesis.