Peptide Bond Formation Using Stable Carboxylic Acid Halides
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Solution Overview
Problem
Existing condensing reagents for forming amide bonds in peptide production, such as pivaloyl chloride, lead to the introduction of by-products, lowering yield and efficiency due to self-decomposition and accumulation of impurities.
Innovation Solution
The use of a carboxylic acid halide with a specific structure, such as a compound represented by formula (I) or (II), where R1, R2, and R3 are aliphatic hydrocarbon groups containing tertiary or quaternary carbon atoms, to form peptide bonds without self-decomposition, allowing for high yield production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If pivaloyl chloride is used as the condensing reagent, then amide bonds can be formed, but by-products are generated that lower the yield
Solution Approach 1:
The patent changes the chemical structure parameters of the condensing reagent from pivaloyl chloride to carboxylic acid halides with specific structural features (formula I or II), thereby eliminating by-product formation while maintaining amide bond formation capability
Solution Approach 2:
The patent employs a condensing reagent that is consumed in the reaction without generating persistent harmful by-products, improving the overall efficiency and economy of the peptide synthesis process
2Productivity
If COMU or isobutyl chloroformate is used as the condensing reagent, then amide bonds can be formed, but heat is generated due to self-decomposition
Solution Approach 1:
The patent changes the chemical stability parameters of the condensing reagent by selecting carboxylic acid halides with specific structural features that resist self-decomposition, thereby eliminating exothermic reactions while maintaining condensation efficiency
Solution Approach 2:
The patent converts the requirement for high reactivity into a benefit by designing a reagent that maintains sufficient reactivity for amide bond formation while incorporating structural features that prevent harmful self-decomposition
3Productivity
If pivaloyl chloride is used repeatedly in peptide production, then multiple amide bonds can be formed, but impurities accumulate as by-products
Solution Approach 1:
The patent changes the chemical structure parameters of the condensing reagent to eliminate by-product formation, enabling repeated use in multi-step peptide synthesis without accumulation of impurities
Solution Approach 2:
The patent enables continuous peptide synthesis by using a condensing reagent that does not generate by-products, allowing multiple amide bond formations to proceed without progressive contamination
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 method achieves high-yield peptide production using a safe condensing reagent that does not generate heat, improving industrial efficiency and reducing impurities.
Implementation Method 1
a step of mixing an N-protected amino acid or an N-protected peptide with a carboxylic acid halide represented by the formula (I)
Implementation Method 2
a step of mixing the product obtained in the step (1) with a C-protected amino acid or a C-protected peptide
Data Source
AI summary
An object of the present invention is to provide a method for producing a peptide with high efficiency, and a method for producing a peptide which comprises the following steps (1) and (2):(1) a step of mixing an N-protected amino acid or an N-protected peptide with a carboxylic acid halide represented by the formula (I)(wherein X represents a halogen atom,R1, R2 and R3 each independently represent an aliphatic hydrocarbon group which may have a substituent, and a total number of the carbon atoms in R1, R2 and R3 is 3 to 40); and(2) a step of mixing the product obtained in the step (1) and a C-protected amino acid or a C-protected peptideis provided.