Lithium Salt Precipitation for High-Purity Protected Peptides

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Solution Overview

Problem

Existing methods struggle to achieve high-purity purification of salts of amino acids and peptide compounds due to the presence of impurities such as β-alanine and its derivatives, which are difficult to remove effectively.

Innovation Solution

A method involving the use of a lithium-containing substance to precipitate a lithium salt of the purification target, which includes amino acids or peptide compounds with protective groups at the N terminus, thereby separating and removing impurities through a lithium salt formation and precipitation process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional purification methods are used to remove impurities such as β-alanine, then the purification process becomes complex and time-consuming, but the purity of the amino acid salt cannot be effectively improved

Engineering Contradiction:
Improvepurity of amino acid saltVSAvoidcomplexity of purification process
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention changes the chemical parameter by converting the amino acid salt to a lithium salt form, which has different solubility characteristics. This parameter change enables selective precipitation of the lithium salt while leaving impurities like β-alanine in solution, achieving high purity without complex purification steps

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention utilizes phase transition by precipitating the lithium salt from the aqueous solution through controlled crystallization. The lithium salt transitions from dissolved state to solid crystalline form, while impurities remain in the liquid phase, enabling effective separation and purification

Inventive Principle:
Principle #36Phase transitions

2Manufacturing precision

If conventional purification methods are used to remove impurities such as β-alanine, then the purification process becomes time-consuming, but the purity of the amino acid salt cannot be effectively improved

Engineering Contradiction:
Improvepurity of amino acid saltVSAvoidpurification time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

By changing the salt form to lithium salt, the invention creates a system where purification occurs through simple precipitation rather than multiple sequential purification steps. This parameter change dramatically reduces the time required while achieving the desired high purity level

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention extracts the purification function into a single step by forming the lithium salt, which naturally separates from impurities through precipitation. This extraction of the purification mechanism into a focused chemical transformation eliminates the need for time-consuming conventional purification sequences

Inventive Principle:
Principle #2Taking out (Extraction)

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

This method achieves high-purity salts of amino acids and peptide compounds by effectively reducing the content of impurities to 5% or less, enhancing their suitability for use in drug discovery and synthetic intermediates.

Implementation Method 1

a step of contacting a lithium-containing substance with a mixture to be purified which is a mixture of the following purification target (i) and the following impurities (ii): (i) the amino acid having a protective group at the N terminus or the peptide compound having a protective group at the N terminus

Methodology Applied
Scientific EffectChemical reaction: Chemical Bonding

Implementation Method 2

a step of precipitating a lithium salt of the purification target

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Data Source

PatentUS20250368680A1Method for producing salt of amino acid or salt of peptide compound or solvate of either one of said salts comprising lithium salt precipitation step
Publication Date: 2025.12.04 CHUGAI PHARMA CO LTD
  • US20250368680A1 patent drawing
  • US20250368680A1 patent drawing
  • US20250368680A1 patent drawing

AI summary

One aspect of the present invention relates to a method for producing a salt of an amino acid or a salt of a peptide compound or a solvate thereof, comprising the following steps (A) and (B): step (A); a step of contacting a lithium-containing substance with a mixture to be purified which is a mixture of the following purification target (i) and the following impurities (ii): (i) the amino acid having a protective group at the N terminus or the peptide compound having a protective group at the N terminus, and (ii) compounds other than the purification target, and step (B); a step of precipitating a lithium salt of the purification target.