S-equol single crystal and preparation method thereof
High-purity and stable S-estradiol single crystals were prepared by solvent-free co-crystallization and single-crystal X-ray diffraction to confirm the configuration. This method solves the problems of unclear crystal form and low accuracy of configuration detection, simplifies the preparation process, and is suitable for industrial applications.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SHANGHAI ERGOTEIN BIOTECHNOLOGY GRP CO LTD
- Filing Date
- 2025-12-08
- Publication Date
- 2026-05-12
AI Technical Summary
In the existing technology, the crystal form of S-estrol is unclear, the accuracy of configuration determination is low, the preparation process is complicated, it is difficult to obtain high-purity and stable single crystals, and there is a lack of simple and feasible configuration determination schemes.
Orthorhombic S-estradiol single crystals were prepared by a solvent-free co-crystallization method. The configuration was confirmed by single-crystal X-ray diffraction combined with Flack parameters. The single crystals were formed by natural evaporation of anhydrous ethanol solvent at room temperature, which simplified the preparation process.
The preparation of high-purity, stable S-estradiol single crystals was achieved with precise determination of crystal form and configuration, simplifying the preparation process and making it suitable for industrial applications.
Smart Images
Figure CN122010889A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of crystal preparation technology, specifically to an S-estradiol single crystal and its preparation method. Background Technology
[0002] S-Estradiol, a key active metabolite of soy isoflavones in the human body, has become a research hotspot in the pharmaceutical and health product fields due to its unique physiological activities. It possesses mild estrogen-like effects, can bidirectionally regulate estrogen levels in the body, and shows significant potential in anti-oxidation, anti-inflammation, improving bone health, and reducing the risk of chronic diseases. It is widely used in the research and development of products for women's health care, anti-aging, and adjunctive treatment of related diseases.
[0003] However, the natural abundance of S-equol is extremely low, and it mostly exists in racemic form. The preparation and purification of optically pure S-equol has always been a technical challenge in the industry. Currently, the acquisition of optically pure S-equol mainly relies on chemical synthesis or biotransformation methods, but the synthesized products often suffer from insufficient purity and difficulty in isomer separation, resulting in limited bioavailability. More importantly, the crystal morphology directly affects the stability, solubility, and consistency of efficacy of the compound. Current research on the crystal structure of S-equol is still incomplete; many reported crystalline products suffer from defects such as co-crystallization with solvents, unclear crystal forms, and poor crystal symmetry, seriously affecting its reliability in pharmaceutical formulation.
[0004] In determining the absolute configuration of optically active compounds, the accuracy of the configuration directly affects their biological activity and safety. Current technologies for S-equorol configuration identification largely rely on indirect methods such as chiral chromatography and nuclear magnetic resonance, which suffer from limited detection accuracy and complex procedures, making it difficult to provide direct evidence of absolute configuration. While single-crystal X-ray diffraction is considered the gold standard for configuration determination, a mature application scheme for S-equorol has not yet been established, lacking clear single-crystal samples and standardized detection procedures.
[0005] Furthermore, existing crystallization processes generally suffer from complex procedures, harsh reaction conditions, and low crystal yields, making it difficult to meet the demands of industrial production for efficient and low-cost preparation of high-purity crystals. Therefore, developing a high-purity, stable, solvent-free S-estrol single crystal, establishing a simple and feasible preparation method, and a precise configuration determination scheme are of great significance for promoting the industrial application of S-estrol and improving the quality and efficacy of related products. This also represents a pressing technical challenge that needs to be addressed in the field. Summary of the Invention
[0006] The purpose of this invention is to address the problems of solvent co-crystallization, unclear crystal form, low accuracy in determining the configuration, and complex preparation process of S-equol in the prior art. This invention provides a solvent-free co-crystallization method with clear crystal system and cell parameters and high purity of S-equol single crystal. It also provides a simple and efficient preparation method and a precise configuration determination scheme to meet the needs of its industrial application.
[0007] To achieve the above objectives, the technical solution adopted by the present invention is: an S-estrol single crystal, characterized in that the single crystal is composed of pure S-estrol molecules, without co-crystallization with solvent molecules, and the single crystal belongs to an orthorhombic crystal system with space group P212121.
[0008] Furthermore, the unit cell parameters of the single crystal are: a=9.225Å, b=9.449Å, c=13.055Å, α=β=γ=90°.
[0009] Furthermore, the R factor of the single crystal is 0.0336-0.0331.
[0010] Furthermore, the single crystal is in the form of clusters or granules and has an asymmetric crystal shape.
[0011] The method for preparing S-estrol single crystals includes the following steps: dissolving S-estrol in anhydrous ethanol to form a solution, then placing the solution in a container and allowing the solvent to evaporate naturally at room temperature until the single crystal is formed.
[0012] Furthermore, the amount of S-estradiol used is 20 mg, and the amount of anhydrous ethanol used is 0.8 mL.
[0013] Furthermore, the container is a quartz test tube.
[0014] Furthermore, the inner diameter of the quartz test tube is 5 mm.
[0015] A method for determining the absolute configuration of S-equorol includes: obtaining an S-equorol single crystal according to any one of claims 1-4, determining the crystal structure of the single crystal using a single-crystal X-ray diffractometer, and calculating a Flack parameter, wherein the Flack parameter is 0.07, thereby confirming that the S-equorol has an S configuration.
[0016] Furthermore, the Flack parameter has a value range of -0.09 to 0.23, and a maximum value of less than 0.5.
[0017] Compared with the prior art, the beneficial effects of the present invention are: 1. The obtained S-equorol single crystal has high purity, no solvent co-crystallization problem, clear crystal system (orthorhombic crystal system), space group (P212121) and unit cell parameters, and the S configuration can be accurately determined by single crystal X-ray diffraction combined with Flack parameters, which solves the problems of ambiguous S-equorol crystal form and low accuracy of configuration detection in the prior art.
[0018] 2. The preparation method is simple and easy to operate. It only requires dissolving S-estradiol in anhydrous ethanol and then allowing the solvent to evaporate naturally at room temperature. No harsh reaction conditions are required, and the dosage ratio is clear. Compared with the existing complex crystallization process, it is more conducive to large-scale preparation. Attached Figure Description Figure 1 This is a crystal diagram of S-estrol as described in this invention. Figure 2 This is a schematic diagram of the structure of S-estrol described in this invention.
Claims
1. An S-estradiol single crystal, characterized in that, The single crystal is composed of pure S-estradiol molecules, without co-crystallization with solvent molecules, and the single crystal belongs to an orthorhombic crystal system with space group P212121.
2. The S-estradiol single crystal according to claim 1, characterized in that, The unit cell parameters of the single crystal are: a=9.225Å, b=9.449Å, c=13.055Å, α=β=γ=90°.
3. The S-estrol single crystal according to claim 1, characterized in that, The R-factor of the single crystal is 0.0336-0.0331.
4. The S-estradiol single crystal according to claim 1, characterized in that, The single crystals are in clusters or granules and have an asymmetric crystal shape.
5. A method for preparing S-estradiol single crystal according to any one of claims 1-4, characterized in that, Includes the following steps: S-Estrol was dissolved in anhydrous ethanol to form a solution, and then the solution was placed in a container and allowed to evaporate naturally at room temperature until the single crystal was formed.
6. The method for preparing S-estradiol single crystal according to claim 5, characterized in that, The amount of S-estradiol used is 20 mg, and the amount of anhydrous ethanol used is 0.8 mL.
7. The method for preparing S-estradiol single crystal according to claim 5, characterized in that, The container is a quartz test tube.
8. The method for preparing S-estradiol single crystal according to claim 7, characterized in that, The inner diameter of the quartz test tube is 5 mm.
9. A method for determining the absolute configuration of S-estradiol, characterized in that, include: Obtain an S-equorol single crystal according to any one of claims 1-4, determine the crystal structure of the single crystal using a single-crystal X-ray diffractometer, and calculate the Flack parameter, wherein the Flack parameter is 0.07, thereby confirming that the S-equorol has an S configuration.
10. The method for determining the absolute configuration of S-estrol according to claim 9, characterized in that, The value of the Flack parameter ranges from -0.09 to 0.23, and the maximum value is less than 0.5.