Iterative synthesis of nitrogen-containing polyketide via oxime intermediates

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Polyketides are typically composed of carbon, hydrogen, and oxygen.
• Nitrogen-containing polyketides exhibit unique properties and biological activities.
• Existing synthetic methods for N-containing polyketides are often structure-specific, limiting broader applications.

Purpose of the Study:

• To develop a general and iterative synthetic strategy for constructing diverse nitrogen-containing polyketides.
• To establish a versatile method for incorporating nitrogen atoms into polyketide frameworks.
• To explore the potential of this method in synthesizing novel bioactive compounds.

Main Methods:

• Iterative chain elongation of carboxylic acids via decarboxylative Claisen condensation.
• Conversion of β-keto groups to O-methyl oximes for nitrogen incorporation.
• Cyclization of oxime intermediates followed by reductive N-O cleavage.

Main Results:

• Successfully constructed carbon frameworks through iterative chain elongation.
• Incorporated nitrogen atoms via O-methyl oxime intermediates.
• Synthesized diverse nitrogen-containing polyketides, including 2-pyridone, 4-aminopyrone, and 4-aminosalicylate.
• Applied the method to synthesize (R)-6-aminomellein, a derivative of a known bioactive compound.

Conclusions:

• The developed iterative synthesis provides a versatile approach to nitrogen-containing polyketides.
• This method allows for the creation of structurally diverse compounds with potential applications in drug discovery.
• The synthetic strategy is applicable to creating novel nitrogen-substituted derivatives of bioactive natural products.