[Stereoselective synthesis of macrolide and polyether antibiotics]

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Context:

• Macrolide and polyether antibiotics are crucial therapeutic agents.
• Existing synthetic routes often lack stereoselectivity and efficiency.
• A common methodology is needed for complex antibiotic synthesis.

Purpose:

• To establish a common, highly stereoselective, and efficient synthetic methodology for macrolide and polyether antibiotics.
• To demonstrate the versatility of the developed methods through the synthesis of various complex aglycons and antibiotics.

Summary:

• The study details the synthesis of macrolide aglycons (methynolide, tylonolide, pikronolide, erythronolide A) using D-glucose, 4-methoxybenzyl (MPM) protecting groups, Yamaguchi esterification, and Wittig-Horner cyclization.
• A novel method for synthesizing substituted tetrahydrofuran and pyran rings was developed for polyether antibiotics, applied to the synthesis of salinomycin, isolasalocid A, and lasalocid A.
• The methodology emphasizes stereochemical control, fragment coupling, and cyclization strategies, with MPM groups playing a key role.

Impact:

• Provides a unified and efficient synthetic approach for a wide range of macrolide and polyether antibiotics.
• Facilitates the production of complex, biologically active natural products.
• Advances the field of stereoselective synthesis and total synthesis of pharmaceuticals.