A Highly Convergent Synthesis Route for Adda: A Non-Proteinogenic Amino Acid Unit in Cyanobacteria

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Natural Product Synthesis

Background:

• Bioactive cyanobacterial peptides contain the unique residue Adda (2-amino-6-dodecanoic-4-methylhexa-3,5-dienoic acid).
• Access to Adda is essential for synthesizing these peptides and for toxicological and environmental studies.

Purpose of the Study:

• To develop a concise and efficient synthesis of Boc-Adda-OH, a protected form of Adda.
• To establish a reliable route for obtaining Adda for research purposes.

Main Methods:

• A nine-step synthetic route was employed.
• Key steps included a regio- and stereoselective intermolecular Heck reaction to form an isoxazolidin-5-one intermediate.
• Subsequent N-O bond cleavage was performed.

Main Results:

• The synthesis successfully produced Boc-Adda-OH in nine steps.
• The Heck reaction provided excellent regio- and stereocontrol.
• The overall approach demonstrated high functional group tolerance.

Conclusions:

• This convergent synthesis provides efficient access to Adda.
• The developed route is suitable for natural product synthesis, environmental monitoring, and toxicological studies.
• The method offers a valuable tool for researchers working with cyanobacterial peptides.