Candida Lipase Alcoholysis for Stable Cortexolone 17α-Monoesters
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Solution Overview
Problem
Existing methods for synthesizing 17α-monoesters of cortexolone and its 9,11-dehydroderivatives are inefficient due to instability and require cumbersome purification processes, such as column chromatography, and hydrolysis in basic environments leads to unwanted by-products.
Innovation Solution
An enzymatic alcoholysis process using Candida lipase is employed to selectively convert 17,21-diesters to 17α-monoesters by reacting substrates in the presence of a lipase from Candida cylindracea and Candida antarctica, which catalyzes the reaction in aprotic solvents, allowing for higher yields and stability of the monoesters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If chemical synthesis methods are used to obtain 17α-monoesters, then the synthesis can be performed, but the monoesters become unstable and require cumbersome purification processes
Solution Approach 1:
The patent replaces chemical synthesis methods with enzymatic catalysis using lipase from Candida. The enzyme selectively catalyzes the formation of 17α-monoesters from 17,21-diesters and corticosteroids, avoiding the instability issues associated with chemical methods. The enzymatic process occurs under mild conditions (pH 7-8, 20-40°C) and provides stable, pure products without requiring cumbersome purification steps.
2Manufacturing precision
If column chromatography is used for purification, then pure monoesters can be obtained, but the process becomes time-consuming and complex
Solution Approach 1:
The lipase enzyme from Candida exhibits high substrate specificity, selectively catalyzing the formation of 17α-monoesters while leaving other positions unchanged. This biochemical selectivity inherently purifies the product during the reaction itself, eliminating the need for time-consuming column chromatography. The enzyme's natural specificity serves the purification function that would otherwise require complex external processes.
3Productivity
If basic environment hydrolysis is used, then diesters can be hydrolyzed, but unwanted by-products are formed
Solution Approach 1:
The patent changes the reaction conditions from basic environment to a neutral to slightly basic pH range (pH 7-8), and from chemical hydrolysis to enzymatic catalysis. The lipase enzyme from Candida operates optimally in this pH range and selectively hydrolyzes only the 21-position ester bond, preventing the formation of unwanted by-products such as 17α,21-diol and 17-monoesters that result from non-selective basic hydrolysis.
4Productivity
If chemical synthesis is used, then monoesters can be produced, but yields are lower due to instability and side reactions
Solution Approach 1:
The patent replaces unstable chemical synthesis with reliable enzymatic catalysis. The lipase from Candida provides consistent, high yields of stable 17α-monoesters by catalyzing the reaction under controlled, mild conditions. The enzyme's specificity and stability under reaction conditions eliminate the side reactions and instability problems that limit chemical synthesis yields.
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 enzymatic process achieves higher yields and stability of 17α-monoesters of cortexolone and its 9,11-dehydroderivatives, providing a more efficient and efficient purification process with higher purity and purity, and stability of the monoesters with higher purity and stability of the monoesters with higher yields and stability of the process.
Implementation Method 1
an enzymatic alcoholysis process using Candida lipase is employed to selectively convert 17,21-diesters to 17α-monoesters by reacting substrates in the presence of a lipase from Candida cylindracea and Candida antarctica
Implementation Method 2
which catalyzes the reaction in aprotic solvents, allowing for higher yields and stability of the monoesters
Data Source
AI summary
The present invention refers to a new enzymatic process for obtaining 17α-monoesters of cortexolone and/or its 9,11-dehydroderivatives starting from the corresponding 17α,21-diesters which comprises an enzymatic alcoholysis reaction. Furthermore, the present invention refers to new crystalline forms of cortexolone-17α-propionate and 9,11-dehydro-cortexolone 17α-butanoate.