DERA Chemoenzymatic Process for High-Purity Chiral Compounds

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Solution Overview

Problem

Existing chemoenzymatic processes using 2-deoxyribose-5-phosphate aldolase (DERA) suffer from poor overall yield and produce mixtures of products, limiting their effectiveness for specific substrates.

Innovation Solution

A process involving the reaction of acetaldehyde with N-protected aminoaldehydes like 3-phthalimidopropionaldehyde under aldolase-catalyzed conditions, using specific DERA aldolases, to form lactols, which are then oxidized and reacted with isopropyl alcohol and acetone to yield isopropyl acetonide esters, achieving high yield and purity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If existing DERA chemoenzymatic processes are used, then chiral compounds can be synthesized, but the overall yield is poor and product mixture is produced

Engineering Contradiction:

Improveoverall yieldVSAvoidproduct purity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent modifies specific parameters of the DERA catalytic system by selecting particular substrates (acetaldehyde and N-protected aminoaldehydes) and optimizing reaction conditions (pH, temperature, solvent composition) to achieve high yield and purity of chiral lactol products, resolving the contradiction between productivity and manufacturing precision

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses N-protected aminoaldehydes as intermediary substrates that undergo controlled aldol condensation with acetaldehyde to form chiral lactols, which can then be converted to desired chiral compounds through subsequent steps, thereby improving both yield and product purity

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If existing DERA processes are used, then chiral compounds can be made, but the process is limited to specific substrates

Engineering Contradiction:

Improvesubstrate rangeVSAvoidprocess effectiveness

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent demonstrates the versatility of DERA by showing it can catalyze aldol condensation reactions with multiple different substrates including acetaldehyde and various N-protected aminoaldehydes (phthalimidopropionaldehyde, succinimido-propionaldehyde, diBoc-aminopropionaldehyde), thereby expanding substrate range while maintaining reliable process effectiveness

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 process enhances yield and specificity, producing high-purity chiral compounds efficiently, overcoming the limitations of previous DERA-based methods.

Implementation Method 1

reacting acetaldehyde with an N-protected aminoaldehyde substrate selected from the group consisting of 3-phthalimidopropionaldehyde, N-formyl-3-aminopropionaldehyde, 3-succinimido-propionaldehyde or N-diBoc-3-aminopropionaldehyde under aldolase-catalyzed aldol condensation conditions

Methodology Applied

Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

Methodology Applied

Scientific EffectAldol condensation: Chemical Bonding

Implementation Method 3

oxidizing the lactol so formed to yield the corresponding lactone

Methodology Applied

Scientific EffectOxidation: Oxidation

Data Source

PatentUS9079877B2Process for preparing chiral compounds

Publication Date: 2015.07.14 VIATRIS SPECIALTY LLC

AI summary

The present invention is directed to a 2-deoxyribose-5-phosphate aldolase (DERA) chemoenzymatic process for making chiral compounds.