First total synthesis of versicotide A, B and C

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Versicotides A-C are natural products featuring anthranilic acid and N-methylalanine (NMe-Ala).
• Their complex structures present synthetic challenges, particularly in forming amide bonds with deactivated aromatic amines.

Purpose of the Study:

• To develop an efficient synthetic route for versicotides A-C.
• To overcome the difficulties associated with coupling reactions involving anthranilic acid derivatives.

Main Methods:

• Solid-phase peptide synthesis (SPPS) utilizing 2-chlorotrityl resin.
• Solution-phase macrocyclization.
• Employing an oxyma additive to facilitate challenging coupling reactions.

Main Results:

• Successful synthesis of versicotides A-C.
• High yields achieved in coupling reactions to the deactivated aromatic amine of o-aminobenzoic acid.
• Avoidance of anthranilic rearrangements and other side reactions.

Conclusions:

• The developed synthetic strategy is effective for producing versicotides A-C.
• The use of an oxyma additive is crucial for efficient coupling in the presence of deactivated aromatic amines.
• This method provides a reliable approach for synthesizing complex natural products containing anthranilic acid moieties.