Synthetic route to scopolamine and/or atropine
Inventors
Blumberg, Shawn T. • MIGUEL, Paul W. • HINOJOSA, Daniel A.
Assignees
Southwest Research Institute SwRI
Publication Number
US-12297195-B2
Publication Date
2025-05-13
Expiration Date
2041-10-07
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Abstract
A synthetic route to scopolamine and/or atropine. In such context, the present invention identifies a method for preparing 6,7-dehydro atropine, which can be converted into either scopolamine and/or atropine, along with a method for converting a protected pyrrole into a tetrachlorobicylic compound, such as benzyl 3-oxo-8-azabicyclo[3.2.1]oct-6-ene-8-carboxylate.
Core Innovation
The invention provides a synthetic route for preparing scopolamine and/or atropine through the preparation of 6,7-dehydro atropine, which serves as a key intermediate. The process begins with the use of a protected pyrrole, which is transformed into a tetrachlorobicyclic compound through reaction with pentachloroacetone. This is followed by reductive dechlorination to obtain a bicyclic compound, which is then subjected to reductive methylation and subsequent conversion steps to yield 6,7-dehydro tropine tosylate and finally 6,7-dehydro atropine.
The 6,7-dehydro atropine obtained from this process can be further converted into either scopolamine or atropine. The method provides details for converting the protected pyrrole into desired intermediates, using steps such as reductive dechlorination, reductive methylation, and coupling reactions with tropic acid. Further steps involve oxidation or reduction to form the final scopolamine or atropine products.
The problem addressed by this invention is the reliance on plant sources such as Atropa belladonna and Duboisia leichhardtii for scopolamine, which yield low amounts and involve laborious extraction processes, as well as supply and cost fluctuations due to agricultural variability. Existing synthetic methods are also limited by the use of expensive or toxic reagents and protecting groups, making large-scale production challenging. The invention aims to circumvent these issues by providing an alternative synthetic route capable of efficiently meeting the growing demand for these compounds.
Claims Coverage
There is one independent claim, covering two main inventive features.
Method for preparing 6,7-dehydro atropine from protected pyrrole
A method that involves: 1. Providing a protected pyrrole where R may be an alkyl, phenyl, or benzyl group. 2. Reacting the protected pyrrole with pentachloroacetone to form a tetrachlorobicyclic compound. 3. Reductive dechlorination of the tetrachlorobicyclic compound to form a second bicyclic compound. 4. Reductive methylation of this compound to form 8-methyl-8-azabicyclo[3.2.1]oct-6-en-3-ol. 5. Conversion of 8-methyl-8-azabicyclo[3.2.1]oct-6-en-3-ol into 6,7-dehydro tropine tosylate. 6. Conversion of 6,7-dehydro tropine tosylate into 6,7-dehydro atropine.
Method of converting a protected pyrrole into a tetrachlorobicyclic compound
A method comprising: - Providing a protected pyrrole where R is an alkyl, phenyl, or benzyl group. - Reacting this protected pyrrole with pentachloroacetone to form a tetrachlorobicyclic compound, where R maintains the identity as an alkyl, phenyl, or benzyl group.
The claims broadly cover synthetic methods for producing 6,7-dehydro atropine and related compounds from protected pyrroles via specific reaction steps, enabling their use as intermediates in the synthesis of scopolamine and/or atropine.
Stated Advantages
The invention offers a significant improvement over current procedures by circumventing reliance on plant sources and more efficiently meeting expanding global demands for nerve agent remedies.
Documented Applications
Preparation of scopolamine and atropine as OPNA (organophosphorous nerve agent) antidotes.
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