Protected Tripeptide Synthesis for High-Purity O-tert-Butyl L-Seryl Glycine

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Solution Overview

Problem

Current methods for preparing O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycine are complex, involve harsh reaction conditions, and result in low yield and purity.

Innovation Solution

A four-step process involving condensation, saponification, and hydrogenation reactions using specific reagents and conditions to synthesize O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycine, including N-benzyloxycarbonyl-O-tert-butyl-L-serine as a raw material, to simplify the process and improve yield and purity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If multi-step synthesis procedures are used to prepare O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycine, then the final compound can be obtained, but the process contains many impurities, is not easy to purify, and has low molar yield

Engineering Contradiction:
Improvepurity of O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycineVSAvoidmolar yield of O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycine
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent optimizes reaction parameters including using specific molar ratios of reagents (N-benzyloxycarbonyl-O-tert-butyl-L-serine to O-tert-butyl-L-serine methyl ester at 1:1.5), controlling reaction temperatures (0-5°C for condensing agent addition, 0-50°C for condensation reaction), and selecting specific solvents to improve both purity and yield simultaneously

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces protected intermediate compounds (N-benzyloxycarbonyl-O-tert-butyl-L-seryl-O-tert-butyl-L-serine methyl ester and N-benzyloxycarbonyl-O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycine benzyl ester) that facilitate the synthesis by preventing side reactions and enabling easier purification, ultimately achieving both high purity and high yield

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If conventional synthesis methods are used, then the reaction can proceed, but harsh reaction conditions are required

Engineering Contradiction:
Improvereaction efficiencyVSAvoidharsh reaction conditions
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent employs mild reaction conditions including conducting condensation reactions at 0-50°C, using mild bases (triethylamine, N,N-diisopropylethylamine), and selecting gentle solvents (dichloromethane, ethyl acetate, acetonitrile, tetrahydrofuran) to avoid harsh conditions while maintaining high reaction efficiency

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses readily available, inexpensive reagents and catalysts such as common condensing agents (EDCI, DCC, HATU, HBTU, CDI) and standard hydrogenation catalysts (Pd/C, Raney nickel) that enable efficient reactions under mild conditions without requiring specialized or harsh materials

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Ease of operation

If the synthesis process is simplified, then the operation becomes easier, but the yield and purity may be affected

Engineering Contradiction:
Improvesimplicity of synthesis processVSAvoidpurity of O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycine
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent divides the synthesis into four clear sequential steps with distinct objectives: (1) condensation to form the dipeptide, (2) saponification to remove protecting groups, (3) condensation to add glycine, and (4) hydrogenation to remove remaining protecting groups. This segmentation makes the process easier to operate while maintaining high purity through controlled progression

Inventive Principle:
Principle #1Segmentation

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 purity and yield of O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycine with simplified operations and mild reaction conditions, making it suitable for industrial production.

Implementation Method 1

carrying out a condensation reaction on N-benzyloxycarbonyl-O-tert-butyl-L-serine and O-tert-butyl-L-serine methyl ester under the action of a condensing agent

Methodology Applied
Scientific EffectCondensation reaction: Chemical Bonding

Implementation Method 2

carrying out a saponification reaction on the N-benzyloxycarbonyl-O-tert-butyl-L-seryl-O-tert-butyl-L-serine methyl ester and an alkaline compound

Methodology Applied
Scientific EffectSaponification reaction: Hydrolysis

Implementation Method 3

carrying out a hydrogenation reaction on the N-benzyloxycarbonyl-O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycine benzyl ester and hydrogen under the action of a catalyst

Methodology Applied
Scientific EffectHydrogenation reaction: Hydrogenation

Data Source

PatentEP4707291A1O-tert-butyl-l-seryl-o-tert-butyl-l-seryl-glycine and preparation method thereof
Publication Date: 2026.03.11 SICHUAN SHIFANG SANGAO BIOCHEMICAL IND CO LTD
  • EP4707291A1 patent drawingFigure 1
  • EP4707291A1 patent drawingFigure 2
  • EP4707291A1 patent drawingFigure 3

AI summary

The present application provides O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-glycine and a preparation method thereof. In the preparation process, N-benzyloxycarbonyl-O-tert-butyl-L-serine and O-tert-butyl-L-serine methyl ester are subjected to a condensation reaction to obtain an intermediate compound represented by formula (I), the compound represented by formula (I) and an alkaline compound are subjected to a saponification reaction to obtain an intermediate compound represented by formula (II), then the intermediate compound represented by formula (II) and glycine benzyl ester p-toluenesulfonate are subjected to a condensation reaction to obtain an intermediate compound represented by formula (III), and finally, the intermediate compound represented by formula (III) and hydrogen are subjected to a hydrogenation reaction to obtain the final product. The preparation method provided by the present application simplifies the process, features simple operation and mild reaction conditions, and reduces the difficulty of industrial production, and it does not involve precious raw materials and is conducive to controlling production costs, and the final product has a high purity and a high yield.