Bioinspired total synthesis of boneratamides A-C

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• Marine natural products often possess unique chemical structures with potential biological activities.
• The pyroglutamic acid moiety is a common structural feature in various bioactive compounds.

Purpose of the Study:

• To achieve the first total synthesis of the marine natural product (+)-boneratamide A.
• To explore a bioinspired Ugi reaction for efficient molecular assembly.
• To synthesize analogs (+)-boneratamide B and (-)-boneratamide C methyl esters.

Main Methods:

• A bioinspired Ugi reaction was employed as the key synthetic step.
• The Ugi reaction utilized (+)-axisonitrile-3, acetone, and L-glutamic acid.
• X-ray crystallography was used to elucidate relative stereochemistries.

Main Results:

• (+)-Boneratamide A was synthesized in 70% yield via a one-pot Ugi reaction.
• The synthesis efficiently formed the amide bond and the γ-lactam ring.
• Analogs (+)-boneratamide B and (-)-boneratamide C methyl esters were also successfully synthesized.

Conclusions:

• The study presents the first successful synthesis of (+)-boneratamide A.
• A bioinspired Ugi reaction provides an efficient route to complex marine natural products.
• The synthetic strategy is applicable to the preparation of related analogs.