Substituted beta-phenyl-alpha-hydroxy propanoic acid, synthesis method and use thereof

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Solution Overview

Problem

Current treatments for cardiovascular and cerebrovascular diseases using salvianic acid derivatives are limited by their inability to effectively cross the cardiocerebral barrier, necessitating the development of modified β-phenyl-α-hydroxylpropionic acid derivatives with enhanced potency and therapeutic effects.

Innovation Solution

A process for synthesizing substituted β-phenyl-α-hydroxy-propionic acid derivatives, specifically compounds with varied functional groups, is developed to enhance their ability to cross biological barriers and improve therapeutic efficacy for cardiovascular and cerebrovascular diseases, involving reactions with specific catalysts and solvents to produce compounds like bornyl β-(3,4-dihydroxylphenyl)-α-hydroxylpropionate ester.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If salvianic acid derivatives are used for treatment of cardiovascular and cerebrovascular diseases, then therapeutic effects are achieved, but the ability to cross cardiocerebral barrier is insufficient

Engineering Contradiction:
Improvetherapeutic effectVSAvoidinability to cross cardiocerebral barrier
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of salvianic acid derivatives by substituting hydroxyl groups with various functional groups (methoxy, ethoxy, halogens, acyloxy) to change the molecular properties. This structural modification enables the derivatives to cross the cardiocerebral barrier while maintaining or enhancing their therapeutic effects on cardiovascular and cerebrovascular diseases

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite molecular structures by combining the core β-phenyl-α-hydroxylpropionic acid scaffold with various substituent groups (R1-R5). These composite structures integrate the pharmacological activity of the parent compound with the barrier-crossing capability of the substituted groups, particularly borneol moieties

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If β-phenyl-α-hydroxylpropionic acid is modified by incorporating borneol structure, then ability to pass through cardiocerebral barrier is improved, but synthesis complexity increases

Engineering Contradiction:
Improveability to pass through cardiocerebral barrierVSAvoidsynthesis complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The synthesis process is divided into distinct stages: first forming the core β-phenyl-α-hydroxylpropionic acid structure, then sequentially introducing substituent groups including borneol moieties. This segmented approach allows each modification step to be optimized independently, managing overall synthesis complexity while achieving the desired barrier-crossing capability

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs various catalysts (concentrated H2SO4, silicotungstic acid, phosphomolybdic acid, p-toluene sulfonic acid, aluminum trichloride, zinc chloride, magnesium chloride) as intermediaries to facilitate the complex substitution reactions. These catalysts enable the incorporation of borneol structures and other functional groups without requiring overly complex synthetic pathways

Inventive Principle:
Principle #24Intermediary (Mediator)

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 synthesized derivatives demonstrate improved potency and therapeutic effects, including increased cerebral microcirculatory blood flow and reduced myocardial infarction areas, suggesting potential for enhanced treatment and prevention of cardiovascular and cerebrovascular diseases.

Implementation Method 1

reacting a compound of the formula (III) with a compound of formula (IV) or a hydrate thereof in the presence of a catalyst

Methodology Applied
Scientific EffectCatalysis: Catalysis

Data Source

PatentEP2514739B1Substituted beta-phenyl-alpha-hydroxy propanoic acid, synthesis method and use thereof
Publication Date: 2016.12.21 NORTHWEST UNIV
  • EP2514739B1 patent drawingFigure 1
  • EP2514739B1 patent drawingFigure 2
  • EP2514739B1 patent drawingFigure 3

AI summary

The present invention relates to a compound of the formula (I), wherein R1, R2 and R3 are each independently selected from H, OH, F, Cl, Br, methoxy and ethoxy; or alternatively, R1 and R2 together form -OCH2O-, R3 is selected from H, OH, methoxy, ethoxy and halogens; R4 is OH or acyloxy; R5 is cycloalkoxyl, amino and substituted amino, and when R5 is selected from amino, at least one of R1, R2 and R3 is not H. The present invention further relates to a process for synthesizing a compound of the formula (I), and use of the compound of the formula (I) in the manufacture of a medicament for the prevention or treatment of cardiovascular or cerebrovascular diseases.