PQQ Synthesis via Oxidizable Pyrroloquinoline Intermediates

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Solution Overview

Problem

Current methods for synthesizing pyrroloquinoline quinone (PQQ) are inefficient and costly due to the high consumption of ammonium cerium nitrate, leading to low yields and high environmental waste, making large-scale industrial production challenging.

Innovation Solution

A new synthesis method that replaces ammonium cerium nitrate with a readily oxidizable substituent, allowing for the oxidation of intermediates under mild conditions without the need for expensive oxidants, using a 4,5-disubstituted-1H-pyrrolo(2,3-f)quinolin-2,7,9-tricarboxylate compound and oxidizing agents like hydrogen peroxide, resulting in higher yields and reduced waste.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ammonium cerium nitrate is used as oxidant for PQQ synthesis, then oxidation reaction can be achieved, but the consumption of oxidant is extremely large (more than 8 times the weight of raw material) and cost is high

Engineering Contradiction:
Improveoxidation reaction effectivenessVSAvoidconsumption of ammonium cerium nitrate
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent changes the chemical structure parameters of the substrate by introducing readily oxidizable substituents (halogens, hydroxyl groups, or alkoxy groups) at positions 4 and 5 of the pyrroloquinoline ring. This structural modification enables the compound to be oxidized more easily, allowing the use of smaller amounts of oxidant (ammonium cerium nitrate) while still achieving effective oxidation to PQQ, thus resolving the contradiction between oxidation effectiveness and oxidant consumption.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If ammonium cerium nitrate is used for PQQ synthesis, then oxidation can be achieved, but the synthesis cost becomes high due to expensive oxidant

Engineering Contradiction:
Improveoxidation reaction effectivenessVSAvoidsynthesis cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

By modifying the molecular structure of the pyrroloquinoline intermediate to include readily oxidizable groups (halogens, hydroxyl, or alkoxy groups), the patent reduces the amount of expensive ammonium cerium nitrate required for oxidation. This structural parameter change directly lowers the synthesis cost while maintaining the effectiveness of the oxidation reaction to produce PQQ.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If ammonium cerium nitrate is used in large amounts, then oxidation reaction proceeds, but waste discharge load increases due to cerium salt waste

Engineering Contradiction:
Improveoxidation reaction effectivenessVSAvoidwaste discharge load
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent introduces readily oxidizable substituents (halogens, hydroxyl groups, or alkoxy groups) at positions 4 and 5 of the pyrroloquinoline ring, which fundamentally changes the oxidation characteristics of the substrate. This structural modification enables the oxidation reaction to proceed with much smaller amounts of ammonium cerium nitrate, thereby significantly reducing the waste discharge load from cerium salt while maintaining effective oxidation to PQQ.

Inventive Principle:
Principle #35Parameter changes

4Quantity of substance

If conventional synthesis routes are used, then PQQ can be produced, but the production scale is limited and industrial production is difficult to achieve

Engineering Contradiction:
ImprovePQQ production amountVSAvoidindustrial production efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent modifies the chemical structure of the pyrroloquinoline intermediate by introducing readily oxidizable groups, which fundamentally improves the oxidation efficiency and reduces oxidant consumption. This structural parameter change enables the process to be scaled up for industrial production, as the reduced oxidant requirement and improved reaction efficiency make large-scale manufacturing economically viable and industrially practical.

Inventive Principle:
Principle #35Parameter changes

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 enables the production of PQQ on a larger scale with higher yields and reduced costs, optimizing both economic and environmental aspects by eliminating the need for expensive oxidants and minimizing waste discharge.

Implementation Method 1

oxidizing PQP with an oxidizing agent to obtain PQQ

Methodology Applied
Scientific EffectOxidation: Oxidation

Data Source

PatentEP3643714B14,5-disubstituted-1-hydro-pyrrole(2,3-f)quinolone-2,7,9-tricarboxylate compound and applications
Publication Date: 2024.01.10 SHANDONG YUANLITAI MEDICAL TECH CO LTD
  • EP3643714B1 patent drawingFigure 1~2
  • EP3643714B1 patent drawingFigure 3~4
  • EP3643714B1 patent drawingFigure 5~6

AI summary

The present invention discloses a 4,5-disubstituted-1H-pyrrolo(2,3-f)quinolin-2,7,9-tricarboxylate compound, or an analog, or derivative thereof, having a structure of Formula I: where R1 and R4 are each independently an atom or group selected from hydrogen, a linear or branched C1-8 alkyl group, a deuterated linear or branched C1-8 alkyl group, an aralkyl group, or a substituted aryl group; R2 is independently an atom or group selected from halogens, a linear or branched C1-8 alkoxy group, or a deuterated linear or branched C1-8 alkoxy group; and R3 is independently an atom or group selected from a linear or branched C1-8 alkoxy group, or a deuterated linear or branched C1-8 alkoxy group. The compound is useful as a reaction intermediate for the synthesis of PQQ, whereby a process in which CAN is used as an oxidant in the synthesis of PQQ in existing patents and literatures is replaced. This makes the whole process cheaper and more efficient.