Flow-Through Photoreactor for Vitamin D Isomerisation
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Solution Overview
Problem
Current methods for large-scale production of calcipotriol face challenges in scaling up photochemical conversions, which are difficult to achieve due to specific reactor and light source design dependencies, leading to inefficiencies and impurities in the isomerization process.
Innovation Solution
The use of a flow-through or continuous flow photoreactor for the photoisomerization of vitamin D analogues, allowing for improved scalability, reduced irradiation time, and increased purity by moving the solution relative to a suitable light source in the presence of a triplet sensitizer, enabling efficient production of calcipotriol.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If a fixed volume batch reactor is used for photoisomerisation, then the process is simple to operate, but the irradiation time is long and product purity is reduced
Solution Approach 1:
The patent transitions from a static batch reactor to a dynamic flow photoreactor system where the solution continuously moves through irradiation zones. This dynamic approach allows optimized light exposure time and intensity, improving photoisomerisation efficiency and product purity while maintaining operational simplicity through continuous automated flow
Solution Approach 2:
The flow photoreactor enables continuous photoisomerisation rather than batch processing. The solution flows continuously through the reactor, receiving constant light exposure, which eliminates idle time between batches and maintains optimal reaction conditions throughout the process, thereby improving purity without complicating operation
2Device complexity
If a fixed volume batch reactor is used for photoisomerisation, then the equipment is simple, but the irradiation time is extended
Solution Approach 1:
The system replaces static batch irradiation with dynamic flow-through irradiation. The solution moves continuously through optimized light paths, ensuring every portion receives adequate exposure in a shorter overall time. The flow rate can be adjusted to optimize the balance between residence time and throughput, reducing total irradiation time without requiring complex equipment
Solution Approach 2:
The patent introduces a temporal dimension to the irradiation process by using continuous flow rather than static batch processing. This allows multiple portions of solution to be irradiated simultaneously in sequence through the flow path, effectively parallelizing the process and reducing total time without increasing device complexity
3Quantity of substance
If photochemical conversions are scaled up using traditional methods, then large-scale production is achieved, but the process becomes difficult to control and efficiency decreases
Solution Approach 1:
The patent divides the large-scale photoisomerisation process into multiple flow modules or stages. Each module handles a portion of the total flow with optimized light exposure, allowing the overall large-scale process to maintain the efficiency of smaller units. This modular segmentation enables scaling up while preserving control and efficiency
Solution Approach 2:
The continuous flow system allows dynamic adjustment of flow rate, residence time, and light intensity to optimize efficiency at any production scale. Unlike static batch processes where scaling simply increases volume and reduces efficiency, the dynamic flow system can be tuned to maintain optimal conditions regardless of scale, thereby preserving productivity
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 convenient large-scale production of calcipotriol with improved purity and reduced irradiation time, overcoming the limitations of traditional batch reactors by allowing for controlled light exposure and operational flexibility.
Implementation Method 1
the hydroxyl protected intermediate IIaaa with (E)-stereochemistry at C-5 is photoisomerised in an unspecified process on a laboratory scale using anthracene as a photocatalyst to give the corresponding (Z)-isomer IIIaaa
Implementation Method 2
irradiation of a solution of a vitamin D derivative of general structure IIa, IIb, IIc, IId or IIe respectively, with a suitable light source in the presence of a triplet sensitizer with a triplet energy in the range of 150-270 kJ/mol
Data Source
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AI summary
The present invention relates to an isomerisation method of vitamin D analogues, such as compounds useful for the synthesis of calcipotriol, and to and to the use of a flow- through photoreactor or continuous flow photoreactor reactor for making said vitamin D analogues. The present invention relates further to the use of intermediates produced with said method for making calcipotriol or calcipotriol monohydrate, or pharmaceutical formulations thereof.