Double annulative cascade of tryptophan-containing peptides triggered by selectfluor

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Biomimetic Chemistry

Background:

• Kapakahines B/F and chaetominine are complex natural products with significant biological relevance.
• Existing synthetic routes often involve multiple steps and challenges in controlling stereochemistry.
• Dearomatization strategies offer potential for efficient construction of complex molecular architectures.

Purpose of the Study:

• To develop a common, efficient, and biomimetic dearomatization strategy for synthesizing kapakahines B/F and chaetominine.
• To generate the tetracyclic α-carboline core in a single synthetic step.
• To gain insights into the diastereoselectivity of the α-carboline fragment formation.

Main Methods:

• A biomimetic strategy employing a selectfluor-mediated dearomatization.
• Activation of N-Phth-Trp-Xaa-OR dipeptides at the C-terminus.
• A pivotal cascade reaction involving double annulation and formation of three carbon-heteroatom bonds.

Main Results:

• Successful generation of the tetracyclic α-carboline core in a single step.
• Demonstration of a common dearomatization strategy applicable to both kapakahines B/F and chaetominine.
• First-time insights into the diastereoselectivity during α-carboline fragment formation.

Conclusions:

• The reported biomimetic dearomatization strategy provides an efficient route to the tetracyclic α-carboline core.
• This approach simplifies the synthesis of complex natural products like kapakahines B/F and chaetominine.
• The study advances the understanding of stereochemical control in α-carboline synthesis.