Narrow Bandwidth Light Photoconversion for Onapristone Synthesis
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Solution Overview
Problem
Current methods for synthesizing onapristone and related compounds are costly and inefficient, with high impurity levels and complex processes, particularly in the photochemical conversion of progesterone receptor antagonists.
Innovation Solution
The use of narrow bandwidth light from sources like excimer Dielectric Barrier Discharge Radiation, LED, or medium pressure mercury lamps at specific wavelengths (280-330 nm) for photoconversion of the C13 methyl group from S to R configuration in compounds of Formula I to Formula II, followed by purification via functionalization and column chromatography, to achieve a higher yield and reduce impurities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional mercury high-pressure lamp is used for photochemical conversion, then the process can be performed, but the yield is only 45-60% and the process is costly
Solution Approach 1:
The patent changes the wavelength parameter of the light source from broad spectrum (250-580 nm) to narrow bandwidth (280-330 nm), specifically targeting 308 nm excimer radiation. This parameter change dramatically improves the yield from 45-60% to 90-95% while reducing costs by eliminating the need for expensive conventional mercury lamps and associated cooling infrastructure.
Solution Approach 2:
The patent employs excimer lamps that emit at 308 nm with narrow bandwidth, replacing expensive conventional mercury lamps. The specific wavelength selection and narrow bandwidth filter approach uses simpler, more cost-effective components compared to the complex conventional lamp system requiring extensive cooling and filtration.
2Reliability
If conventional photochemical conversion is used, then the reaction can proceed, but impurity levels are high and separation is complex
Solution Approach 1:
By changing the wavelength parameter to narrow bandwidth 280-330 nm (specifically 308 nm), the patent achieves high selectivity for the desired photochemical transformation. This produces minimal polar impurities compared to broad spectrum irradiation, dramatically simplifying the purification process and reducing the complexity of separation equipment needed.
3Productivity
If broad spectrum light (250-580 nm) is used for photoconversion, then the process can be performed, but the yield is low and impurities are high
Solution Approach 1:
The patent applies parameter change by restricting the light wavelength to a narrow bandwidth of 280-330 nm, centered at 308 nm excimer radiation. This selective wavelength targeting the C13 methyl group photoconversion achieves 90-95% yield with high stereoselectivity for the desired isomer, compared to only 45-60% yield with broad spectrum light.
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 increases the yield of the desired compound (Formula II) to 90-95%, reducing synthesis costs and simplifying the separation process, while generating fewer polar impurities, thus improving the efficiency and cost-effectiveness of steroid synthesis, including onapristone.
Implementation Method 1
narrow bandwidth light from a lamp (e.g., excimer Dielectric Barrier Discharge Radiation Source (DBD), (Light-Emitting Diode) LED lamp, OLED (Organic Light-Emitting Diode) lamp, or medium pressure mercury lamp (optionally with filters and at a wavelength of about 280 nm to about 330 nm)) is used to irradiate the compound of Formula I to convert the compound of Formula I to the compound of Formula II
Data Source
AI summary
Methods and systems for making intermediates in the synthesis of onapristone are provided. Aspects include the photoconversion of onapristone synthesis intermediates using a narrow band frequency light source.