Deuterated Vinyl Hydroxy Ester Synthesis for NMR Signal Enhancement
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Solution Overview
Problem
Current methods for hyperpolarizing metabolites for NMR signal enhancement, such as PHIP, face challenges in achieving high signal enhancements and cost-effectiveness due to the lack of suitable precursor molecules, particularly vinylated hydroxy esters that are deuterated and isotopically labeled, which are essential for optimal signal enhancements.
Innovation Solution
A method for synthesizing vinylated hydroxy esters through vinylation of compounds using vinyl acetate, followed by cleavage and conversion steps, allowing for the production of deuterated intermediates and final products suitable for hyperpolarized agents, which can enhance NMR signals effectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If PHIP technique is used to hyperpolarize metabolites, then production cost and time are reduced compared to DNP, but signal enhancement is one order of magnitude lower
Solution Approach 1:
The patent modifies the molecular structure of precursors by introducing deuterium at specific positions (vinyl group and carboxylic acid carbon) and using isotopically labeled compounds. This changes the physical and chemical parameters of the molecules to optimize their suitability for PHIP hyperpolarization, thereby enhancing signal intensity while maintaining the fast production capability of PHIP
Solution Approach 2:
The invention uses composite approaches by combining deuterated vinyl groups with isotopically labeled hydroxy esters in a single molecular structure. This composite molecular design creates precursor molecules that simultaneously possess the structural features needed for fast PHIP polarization and the isotopic composition required for high signal enhancement
2Measurement precision
If deuterated vinyl hydroxy esters are synthesized using conventional methods, then signal enhancement is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The synthesis process is divided into discrete, manageable steps: (1) vinylation of hydroxy esters to form vinyl hydroxy esters, (2) deuterium introduction at specific positions, and (3) isotopic labeling. This segmentation allows each step to be optimized independently and simplifies the overall manufacturing process compared to conventional one-step methods
Solution Approach 2:
The patent employs vinyl hydroxy esters as intermediary compounds that serve as precursors for the final hyperpolarized metabolites. These intermediaries are specifically designed to be compatible with PHIP hyperpolarization conditions, facilitating the transformation from stable precursor to hyperpolarized product while maintaining high signal enhancement
3Measurement precision
If vinyl carboxylic acids are used as precursors for PHIP, then signal enhancement is optimized, but deuterium labeling has not been achieved
Solution Approach 1:
The patent performs deuterium labeling and isotopic enrichment during the synthesis of vinyl hydroxy esters before the final hyperpolarization step. By incorporating deuterium at the vinyl group and carboxylic acid carbon positions during precursor synthesis, the molecules are pre-prepared for optimal PHIP hyperpolarization, achieving both deuterium labeling and high signal enhancement
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 method achieves high yields (>80%) of deuterated vinyl hydroxy esters, enabling cost-effective production of hyperpolarized agents that enhance NMR signals, overcoming previous limitations in precursor availability and signal enhancement.
Implementation Method 1
cleaving Z by using UV light
Implementation Method 2
converting Q into an alcohol in the presence of nitrite, or converting Q into bromine in the presence of nitrite followed by hydrolysis
Data Source
AI summary
The present invention relates to a method for preparing a compound suitable for signal enhanced magnetic resonance imaging comprising the steps of vinylating a mono-, di- or tricarboxylic acid comprising a moiety -Q-Z with Q being O or N and Z being a protecting group by using vinyl acetate, cleaving Z, and if Z has not already been converted into an alcohol upon cleavage, converting Q into an alcohol either by using nitrite or by converting Q into bromine followed by hydrolysis yielding a vinyl hydroxy ester. The compounds used may be partly or fully deuterated. Furthermore, the present invention relates to a vinyl hydroxy ester as well as an intermediate of its synthesis, wherein the vinyl moiety of the vinyl hydroxy ester and of the intermediate is partly or fully deuterated.