Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

Area of Science:

• Natural Product Chemistry
• Synthetic Organic Chemistry
• Microbiology
• Chemical Biology

Background:

• Longicatenamides A-D are cyclic hexapeptides produced by a co-culture of *Streptomyces* sp. KUSC_F05 and *Tsukamurella pulmonis* TP-B0596.
• These peptides are not produced in monocultures, highlighting their role in microbial chemical communication.
• Understanding the chemical structures and biological activities of such compounds is crucial for exploring inter-microbial interactions.

Purpose of the Study:

• To achieve the first total synthesis of longicatenamide A.
• To structurally confirm longicatenamide A through chemical synthesis.
• To evaluate the antimicrobial activity of the synthesized longicatenamide A.

Main Methods:

• Chemical synthesis of non-commercially available building blocks with stereocontrol.
• Fmoc-based solid-phase peptide synthesis for peptide chain elongation.
• Solution-phase cyclization followed by simultaneous deprotection to yield longicatenamide A.
• Chromatographic analysis for structural verification.

Main Results:

• Successful solid-phase total synthesis of longicatenamide A was achieved.
• The chemical structure of longicatenamide A was corroborated by chromatographic analysis.
• The synthesized longicatenamide A demonstrated confirmed antimicrobial activity.

Conclusions:

• The total synthesis provides definitive structural confirmation of longicatenamide A.
• The developed solid-phase synthesis methodology enables efficient production of longicatenamide A.
• This synthetic approach is expected to facilitate the creation of diverse analogues for further research into microbial communication and drug discovery.