Concise Total Synthesis of (+)-Bionectins A and C

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Epipolythiodiketopiperazines (ETPs) are a class of natural products with diverse biological activities.
• The total synthesis of complex natural products like (+)-bionectins A and C presents significant challenges.

Purpose of the Study:

• To achieve the concise and efficient total synthesis of (+)-bionectins A and C.
• To develop scalable and novel synthetic methodologies applicable to ETPs and related compounds.

Main Methods:

• Development of a scalable synthesis for *erythro*-β-hydroxytryptophan.
• Application of an intramolecular Friedel-Crafts reaction for indole functionalization.
• Introduction of a new mercaptan reagent for mild ETP ring formation and cleavage.

Main Results:

• Successful total synthesis of (+)-bionectin A and C.
• Demonstration of a novel intramolecular Friedel-Crafts indolylation.
• First report of permanganate-mediated stereoinvertive hydroxylation of diketopiperazine α-stereocenters.
• First synthesis of a triketopiperazine directly from a *cyclo*-dipeptide.

Conclusions:

• The developed synthetic strategies are efficient and scalable.
• New insights into the chemistry of ETPs and diketopiperazines were gained.
• The synthesis and X-ray analysis of (+)-bionectin A prompted reevaluation of its original characterization.