Solid phase synthesis of globomycin and SF-1902 A5

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Antibiotic Discovery

Background:

• Globomycin and SF-1902 A(5) are natural lipocyclodepsipeptide antibiotics.
• These compounds target the enzyme signal peptidase II, crucial for bacterial processes.
• Developing efficient synthetic routes is key to exploring their therapeutic potential.

Purpose of the Study:

• To report the total syntheses of globomycin and SF-1902 A(5).
• To develop a versatile synthetic platform for generating antibiotic analogs.
• To facilitate the discovery of new signal peptidase II inhibitors.

Main Methods:

• Solid-phase peptide synthesis for the peptidic fragment.
• Asymmetric epoxidation methodology for the lipidic chain construction.
• Solid-phase fragment coupling and macrolactonization for final assembly.

Main Results:

• Successful synthesis of globomycin and SF-1902 A(5).
• Demonstrated feasibility of solid-phase fragment linkage and macrolactonization.
• Established a platform for rapid analog library generation.

Conclusions:

• The developed synthetic strategy provides efficient access to globomycin and SF-1902 A(5).
• The methodology allows for facile structural modifications, aiding in the search for novel antibiotics.
• This work supports the development of new signal peptidase II inhibitors for therapeutic applications.