Boronic Ester Metathesis for Compound Library Synthesis

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Solution Overview

Problem

Current methods for synthesizing compound libraries, such as combinatorial chemistry, face challenges in efficiently and quantitatively producing diverse compounds with specific properties, particularly in the discovery of bioactive molecules, as they often require multiple steps and can be hindered by the need for catalysts and harsh conditions.

Innovation Solution

A new boronic ester metathesis reaction is developed, which can be performed at ambient temperature with or without a catalyst, allowing for the rapid and quantitative preparation of compound libraries by exchanging substituents on dioxaborolane or dioxaborinane rings, enabling the generation of multiple compounds with varying structures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If combinatorial chemistry methods are used to synthesize compound libraries, then a large number of compounds can be produced, but the process requires multiple steps and harsh conditions that reduce efficiency

Engineering Contradiction:
Improvecompound library synthesis efficiencyVSAvoidsynthesis process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention changes the reaction parameters by using boronic ester metathesis that proceeds under mild conditions (ambient temperature, no catalyst required) compared to traditional combinatorial chemistry methods that require harsh conditions and multiple steps. This parameter change simplifies the synthesis process while maintaining high productivity in compound library generation.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If traditional boronic ester exchange reactions are used, then compound libraries can be prepared, but the reactions require catalysts and harsh conditions that complicate the process

Engineering Contradiction:
Improvesynthesis process simplicityVSAvoidharsh reaction conditions
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and eliminates the requirement for catalysts and harsh conditions from the boronic ester exchange reaction. The discovered metathesis reaction proceeds without catalysts under mild conditions, removing the harmful factors associated with traditional methods while maintaining the ability to prepare compound libraries efficiently.

Inventive Principle:
Principle #2Taking out (Extraction)

3Adaptability or versatility

If multiple synthesis steps are used to generate diverse compounds, then compound diversity is achieved, but the time and resources required increase significantly

Engineering Contradiction:
Improvecompound structure diversityVSAvoidsynthesis time
Core Design Contradiction:
Adaptability or versatilityVSLoss of time

Solution Approach 1:

The invention employs preliminary action by preparing boronic esters with different substituents in advance, which can then be rapidly exchanged through metathesis to generate diverse compounds. This approach allows compound diversity to be achieved through simple exchange reactions rather than time-consuming multi-step syntheses, significantly reducing the time and resources required.

Inventive Principle:
Principle #10Preliminary action

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 approach simplifies the synthesis process, reduces the need for catalysts and harsh conditions, and facilitates the production of diverse compounds, enhancing the efficiency and productivity in discovering bioactive molecules by allowing for the formation of complex structures with varying properties.

Implementation Method 1

a boronic ester metathesis reaction has been discovered that can be carried out at ambient temperature, with or without catalyst, enabling new compounds to be easily prepared

Methodology Applied
Scientific EffectMetathesis reaction: Chemical Bonding

Data Source

PatentEP3337810B1Compound library preparation process based on exchange reaction between diferently substituted dioxaborolanes or dioxaborinanes
Publication Date: 2021.03.24 CENT NAT DE LA RECH SCI (C N R S)
  • EP3337810B1 patent drawingFigure 1~2
  • EP3337810B1 patent drawingFigure 3~4
  • EP3337810B1 patent drawingFigure 5~6

AI summary

The present invention relates to the preparation of a compound library comprising the following steps: • i. Having available at least two different compounds each comprising at least a dioxaborolane or dioxaborinane ring. In said compounds: • -the boron of the dioxaborolane or dioxaborinane ring is directly linked to a carbon atom of a hydrocarbon radical; • -at least one carbon atom of the dioxaborolane or dioxaborinane ring is monosubstituted, the other carbon atoms are non- substituted or monosubstituted; • -in at least two compounds, the hydrocarbon radicals linked to the boron are different; • - in at least two compounds, either the dioxaborolane or dioxaborinane ring carbon atoms are differently substituted and/ or the size varies. • ii. Reacting the compounds of step (i.) and forming, by a boronic ester metathesis reaction, the library comprising at least four different compounds. The present invention also relates to a compound library. Illustrative for the present invention is the following figure: