Solid-Phase Synthesis of Aromatic-Ring Peptide Derivatives

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Solution Overview

Problem

Existing liquid phase synthesis methods for compounds with an aromatic 6-membered ring, such as thiopeptides, are inefficient for producing a wide variety of derivatives due to the need for individual preparation of peptide sequences and complex purification processes.

Innovation Solution

A solid-phase synthesis method involving reacting an amino acid or peptide bonded to a solid-phase carrier with a specific compound to form a peptide including an aromatic 6-membered ring, followed by deprotection, amino acid condensation, and cyclization reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If liquid phase synthesis method is used for thiopeptides, then synthesis of specific compound is achieved, but synthesis of wide variety of derivatives is difficult and purification is complicated

Engineering Contradiction:
Improveability to synthesize wide variety of derivativesVSAvoidcomplexity of purification operation
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent introduces a solid-phase carrier as an intermediary support for peptide synthesis. The peptide sequence is synthesized while attached to the solid-phase carrier, which acts as a mediator that simplifies purification by allowing easy separation of the synthesized peptide from reaction byproducts through filtration, thereby enabling versatile synthesis of multiple derivatives without complicated purification operations for each compound

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If liquid phase synthesis method is used, then specific peptide sequence is synthesized, but individual preparation for each target peptide is required

Engineering Contradiction:
Improveefficiency of derivative productionVSAvoidtime for individual preparation
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent applies universality by using a standardized solid-phase synthesis platform that can synthesize multiple different peptide sequences using the same basic methodology and reagents. By attaching different amino acid sequences to the same type of solid-phase carrier and using universal coupling reagents, the system enables efficient production of various thiopeptide derivatives without requiring individual preparation procedures for each target peptide

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Manufacturing precision

If liquid phase synthesis is used, then synthesis reaction is performed, but complicated purification operation is required to remove impurities

Engineering Contradiction:
Improvepurity of synthesized compoundVSAvoidsimplicity of purification operation
Core Design Contradiction:
Manufacturing precisionVSEase of operation

Solution Approach 1:

The solid-phase carrier serves as an intermediary that facilitates simplified purification. After synthesis on the solid-phase carrier, the peptide can be cleaved from the carrier and purified by simple filtration and washing steps, which effectively remove impurities without requiring complicated purification operations, thus achieving high purity with ease of operation

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP4596566A1Compound production method
Publication Date: 2025.08.06 THE UNIV OF TOKYO
  • EP4596566A1 patent drawingFigure 1a~1c
  • EP4596566A1 patent drawingFigure 2a~2c
  • EP4596566A1 patent drawingFigure 3

AI summary

The present invention provides a method which makes it possible to simply produce a peptide including an aromatic 6-membered ring in the backbone. The present invention relates to a production method for a compound represented by Formula (I), the method including reacting an amino acid or amino acid derivative, or a peptide, which is bonded to a solid-phase carrier and has a free amino group, or a solid-phase carrier having a free amino group with a compound represented by Formula (1) to obtain a compound represented by Formula (2), in which a compound obtained by deprotecting PG of the compound represented by Formula (2) is optionally subjected to one or more amino acid condensation reactions and then is cleaved from the solid-phase carrier to perform a cyclization reaction.