Cholic Acid Synthesis via Steroid Intermediates
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for synthesizing cholic acid derivatives, such as ursodeoxycholic acid, tauroursodeoxycholic acid, and obeticholic acid, are cumbersome and inefficient, requiring multiple reactions and involving complex processes.
Innovation Solution
The development of compounds and methods that utilize specific chemical structures and reactions to convert 5β, 7-keto or 5,6-dehydro, 7-keto compounds into cholic acid derivatives, including ursodeoxycholic acid, 7-ketolithocholic acid, and obeticholic acid, through steps like reducing double bonds, hydrolyzing electronegative groups, and forming carboxylic acids or esters, to streamline the synthesis process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If multiple reactions and complex processes are used to synthesize cholic acid derivatives, then the synthesis can achieve the desired products, but the process becomes cumbersome and inefficient
Solution Approach 1:
The patent segments the synthesis process into distinct functional modules: (1) preparation of 5β,7-keto or 5,6-dehydro-7-keto compounds as key intermediates, (2) selective reduction of carbonyl groups to hydroxyl groups using borohydride reagents, (3) hydrolysis of electronegative groups, and (4) formation of carboxylic acid or ester groups. This segmentation allows each step to be optimized independently and facilitates streamlined production of multiple cholic acid derivatives from common intermediates.
Solution Approach 2:
The patent creates universal intermediates (5β,7-keto and 5,6-dehydro-7-keto compounds) that can serve as starting materials for multiple different cholic acid derivatives. These intermediates can be converted to various products including ursodeoxycholic acid, tauroursodeoxycholic acid, 7-ketolithocholic acid, and obeticholic acid through systematic modification, reducing the need for separate synthesis routes for each derivative.
2Productivity
If multiple reactions and complex processes are used to synthesize cholic acid derivatives, then the desired products can be obtained, but the time required for synthesis increases
Solution Approach 1:
The patent performs preliminary actions by preparing the 5β,7-keto or 5,6-dehydro-7-keto compounds in advance as versatile intermediates. These pre-prepared intermediates contain the core steroid skeleton with strategically positioned functional groups that can be rapidly transformed into different cholic acid derivatives through standardized reaction sequences, eliminating the need to build the entire molecular framework repeatedly for each derivative.
Solution Approach 2:
The patent employs parameter changes in the form of selective chemical transformations: reducing carbonyl groups to hydroxyl groups using borohydride reagents under controlled conditions, hydrolyzing electronegative groups to carboxylic acids or esters, and modifying side chains. These parameter changes allow rapid interconversion between different derivatives from the same intermediate structure.
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
These methods provide a more efficient and streamlined process for producing cholic acid derivatives, improving the synthesis efficiency and reducing the complexity of existing processes.
Implementation Method 1
reducing the 5,6-alkene double bond to a dihydro product with 5β stereochemistry; reducing the 3-ketone to a 3α-hydroxyl; reducing the 7-ketone to a 7β-hydroxyl
Implementation Method 2
hydrolyzing the electronegative groups at the 3-position to give a 3-ketone; hydrolyzing the electronegative groups at the 3-position to produce a 3-ketone
Implementation Method 3
reducing the 5,6-alkene double bond to a dihydro product with 5β stereochemistry
Data Source
AI summary
Methods of making cholic acid derivatives, particularly ursodeoxycholic acid, tauroursodeoxycholic acid, 7-ketolithocholic acid, obeticholic acid, their carboxylate salts and carboxylate esters, and starting materials and intermediates therefor.