Synthesis of complex nucleoside antibiotics

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Nucleoside antibiotics are crucial in treating bacterial infections.
• Developing efficient synthetic routes for complex nucleoside antibiotics is essential.
• Existing methods may lack regioselectivity or require harsh conditions.

Purpose of the Study:

• To synthesize undecose nucleoside antibiotics Herbicidin B and tunicaminyluracil.
• To develop and apply a samarium diiodide (SmI2)-mediated aldol reaction for complex molecule synthesis.
• To establish a synthetic strategy for caprazol, the core of caprazamycins, and generate analogues for antibacterial drug discovery.

Main Methods:

• Samarium diiodide (SmI2)-mediated aldol reaction utilizing alpha-phenylthioketone as an enolate.
• Regioselective enolate generation under near-neutral conditions.
• Beta-selective ribosylation without neighboring group participation and modified reductive amination for diazepanone construction.

Main Results:

• Successful synthesis of Herbicidin B and fully protected tunicaminyluracil.
• Demonstration of the SmI2-mediated aldol reaction's power in synthesizing complex nucleoside antibiotics.
• Construction of caprazol, the core structure of caprazamycins, via a novel synthetic route.

Conclusions:

• The SmI2-mediated aldol reaction is a versatile and efficient tool for synthesizing complex nucleoside antibiotics.
• The developed synthetic strategy for caprazol and its analogues offers a promising avenue for novel antibacterial agents.
• This research provides key structural analogues to define pharmacophores for improved antibacterial drug development.