Water-Soluble Ynamide Coupling Reagent Peptide Synthesis
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Solution Overview
Problem
Traditional coupling reagents for peptide synthesis, such as N,N'-dicyclohexylcarbodiimide, produce by-products with poor solubility, requiring complex post-treatment and additional additives that reduce atom economy and increase costs and environmental impact.
Innovation Solution
Development of a water-soluble ynamide coupling reagent with a structure represented by formula (I), which allows for easy preparation and no additional additives, and can be removed by washing with water after hydrolysis, simplifying the post-treatment process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If traditional carbodiimide coupling reagents (e.g., DCC) are used, then amide bond formation is achieved, but the by-product has poor solubility and requires complex post-treatment
Solution Approach 1:
The patent modifies the molecular structure of carbodiimide coupling reagents by introducing water-soluble groups (such as sulfonate, carboxylate, or ammonium salt groups) to change the solubility parameter of the by-product. This structural modification enables the by-product to be removed by simple water washing instead of requiring complex column chromatography or centrifugation procedures.
Solution Approach 2:
The patent converts the traditionally harmful effect of poor solubility into a beneficial feature by designing the by-product to be highly water-soluble. This allows the by-product to be easily separated from the organic phase containing the desired product, transforming what was previously a separation difficulty into a simple aqueous washing step.
2Productivity
If additional additives (alkalis and racemization suppressors) are used to improve reaction effects, then reaction efficiency is enhanced, but atom economy is reduced and costs increase
Solution Approach 1:
The patent designs the coupling reagent to perform multiple functions simultaneously: it activates the carboxylic acid, suppresses racemization, and provides its own base component. This multi-functional design eliminates the need for separate additives, improving atom economy while maintaining high reaction efficiency and preventing racemization of chiral centers.
Solution Approach 2:
The patent merges the functions of the coupling reagent, base, and racemization suppressor into a single molecular structure. By combining these previously separate components into one integrated reagent, the patent reduces the number of additional substances required and improves atom economy without sacrificing reaction performance.
3Manufacturing precision
If column chromatography is used for product purification, then high purity product is obtained, but time consumption and cost increase
Solution Approach 1:
The patent changes the solubility parameter of the by-product by incorporating water-soluble groups into the coupling reagent structure. This modification enables simple aqueous washing to achieve separation with sufficient purity for most applications, eliminating the need for time-consuming column chromatography while maintaining acceptable product quality.
4Ease of manufacture
If conventional coupling reagents are used, then amide synthesis is achieved, but environmental impact increases due to organic solvent requirements
Solution Approach 1:
The patent changes the solubility characteristics of the by-product to be water-soluble, enabling aqueous washing instead of organic solvent-based purification methods. This parameter change significantly reduces the use of volatile organic solvents, thereby lowering environmental impact while maintaining synthesis feasibility and product purity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The water-soluble ynamide coupling reagent facilitates efficient peptide synthesis with high purity and yield, minimizing racemization and environmental impact by eliminating the need for column chromatography and reducing the use of organic solvents.
Implementation Method 1
the by-product could be removed by washing with water, and a preparation method and use thereof... whose by-product could be removed by washing with water
Data Source
AI summary
The present disclosure discloses a water-soluble ynamide coupling reagent and a method for using the water-soluble ynamide coupling reagent in the synthesis of amide, polypeptide, ester and thioester compound. The ynamide coupling reagent has the structure represented by the following formula (I):and in the formula (I), R is one selected from the group consisting of methylsulfonyl, benzenesulfonyl, p-toluenesulfonyl, trifluoroacetyl and other electron withdrawing groups.