Scalable Access to Arylomycins via C-H Functionalization Logic.

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Natural Products

Background:

• Arylomycins are potent antibacterial natural products in preclinical development.
• Existing synthesis routes are complex, costly, and time-consuming for scaling.
• Simplified access to arylomycin analogues is crucial for further research.

Purpose of the Study:

• To develop a streamlined synthetic route to arylomycin analogues.
• To enable scalable production of these promising antibacterial agents.
• To synthesize and evaluate novel arylomycin analogues.

Main Methods:

• Copper-mediated oxidative phenol coupling for macrocyclization.
• C-H functionalization logic for simplified synthesis.
• Gram-scale synthesis and formal total synthesis of arylomycins.

Main Results:

• A novel, operationally simple, and scalable synthetic route was established.
• The largest macrocyclization of its kind was achieved.
• A collection of new arylomycin analogues were synthesized and biologically evaluated.

Conclusions:

• The new synthetic strategy significantly simplifies arylomycin analogue production.
• This approach facilitates the development of novel antibacterial agents.
• The method is amenable to large-scale synthesis for preclinical development.