Total synthesis of (+)-mycalamide A

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Natural Product Synthesis

Background:

• (+)-Mycalamide A is a complex natural product with potential biological activities.
• Efficient and scalable synthetic routes are crucial for further investigation of such molecules.

Purpose of the Study:

• To develop a convergent total synthesis of (+)-mycalamide A.
• To establish novel methodologies for constructing key structural motifs.

Main Methods:

• Convergent synthesis strategy.
• Yb(OTf)3-TMSCl catalytic system for trioxadecalin ring formation.
• One-pot delta-lactonization for tetrahydropyran ring construction.
• Utilized d-mannitol as a common starting material.

Main Results:

• Successfully synthesized the right segment (trioxadecalin) and the left segment (tetrahydropyran) of (+)-mycalamide A.
• Developed a novel delta-lactonization protocol.
• Achieved coupling of the segments and functional group transformations to yield the target molecule.

Conclusions:

• A practical and efficient total synthesis of (+)-mycalamide A has been achieved.
• The developed methodologies offer valuable tools for the synthesis of related complex molecules.
• The synthesis highlights the utility of d-mannitol as a versatile chiral pool starting material.