Search

CN-122010889-A - S-equol monocrystal and preparation method thereof

CN122010889ACN 122010889 ACN122010889 ACN 122010889ACN-122010889-A

Abstract

The invention discloses an S-equol monocrystal and a preparation method thereof, and relates to the technical field of crystal preparation. An S-equol single crystal, which consists of pure S-equol molecules, is not co-crystallized with solvent molecules, belongs to an orthorhombic system, has a space group of P212121, and has unit cell parameters of a= 9.225 a, b= 9.449 a, c= 13.055 a, α=β=γ=90°. The obtained S-equol monocrystal has high purity, no solvent co-crystallization problem, clear crystal system (orthorhombic system), space group (P212121) and unit cell parameters, and can accurately determine the S configuration by combining single crystal X-ray diffraction with the Flack parameter, thereby solving the problems of S-equol Ma Fenjing type blurring and low configuration detection precision in the prior art.

Inventors

  • ZHANG WEI
  • WU MENGYAO

Assignees

  • 上海麦角硫因生物科技集团有限公司

Dates

Publication Date
20260512
Application Date
20251208

Claims (10)

  1. 1. An S-equol single crystal, characterized in that the single crystal is composed of pure S-equol molecules, is not co-crystallized with solvent molecules, and belongs to an orthorhombic system, and the space group is P212121.
  2. 2. The S-equol single crystal of claim 1, wherein the single crystal has unit cell parameters of a= 9.225 a, b= 9.449 a, c= 13.055 a, α=β=γ=90°.
  3. 3. The S-equol single crystal of claim 1, wherein the single crystal has an R factor of 0.0336-0.0331.
  4. 4. The S-equol single crystal of claim 1, wherein the single crystal is in a cluster or granule form and has an asymmetric crystal shape.
  5. 5. A process for preparing a single crystal of S-equol according to any one of claims 1-4, comprising the steps of dissolving S-equol in absolute ethanol to form a solution, and then placing the solution in a container, and naturally volatilizing the solvent at room temperature until the single crystal is formed.
  6. 6. The method for producing a single crystal of S-equol according to claim 5, wherein the amount of S-equol is 20mg and the amount of absolute ethyl alcohol is 0.8mL.
  7. 7. The method for preparing a single crystal of S-equol according to claim 5, wherein the container is a quartz tube.
  8. 8. The method for producing a single crystal of S-equol according to claim 7, wherein the inner diameter of the quartz tube is 5mm.
  9. 9. A method for determining the absolute configuration of S-equol, comprising obtaining the S-equol single crystal of 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-equol has the S configuration.
  10. 10. The method of claim 9, wherein the value of the fly parameter is in the range of-0.09 to 0.23 and the maximum value is less than 0.5.

Description

S-equol monocrystal and preparation method thereof Technical Field The invention relates to the technical field of crystal preparation, in particular to an S-equol monocrystal and a preparation method thereof. Background S-equol is taken as a key active metabolite of soybean isoflavone in human body, and becomes a research hot spot in the field of medicines and health care products by virtue of the unique physiological activity of the S-equol. The compound has a mild estrogen-like effect, can bidirectionally regulate the estrogen level in the body, has remarkable potential in the aspects of resisting oxidation, resisting inflammation, improving bone health, reducing the risk of chronic diseases and the like, and is widely applied to the development of products for female health care, anti-aging health care and related disease auxiliary treatment. However, the naturally occurring amounts of S-equol are very low and are often present in the form of racemates, and the preparation and purification of optically pure S-equol has been an industrial technical difficulty. In the prior art, the acquisition of optically pure S-equol mainly depends on a chemical synthesis or biological conversion method, but the synthesized product often has the problems of insufficient purity, high isomer separation difficulty and the like, so that the bioavailability of the product is limited. More critical is that the crystal morphology directly affects the stability, solubility and drug effect consistency of the compound, but the current research on S-equol crystals is not perfect, and the reported crystal products have defects of co-crystallization with solvents, undefined crystal forms, poor symmetry of crystals and the like, which seriously affects the application reliability in the preparation production. In absolute configuration determination, the configuration accuracy of an optically active compound is directly related to its biological activity and safety. In the prior art, the configuration identification of S-equol is dependent on chiral chromatography, nuclear magnetic resonance and other indirect methods, and has the problems of limited detection precision, complex operation flow and the like, so that direct evidence of absolute configuration is difficult to provide. The single crystal X-ray diffraction method is used as a gold standard for configuration determination, a mature application scheme is not formed in the field of S-equol, and a definite single crystal sample and a standardized detection flow are lacked. In addition, the existing crystallization process generally has the problems of complex flow, harsh reaction conditions, low crystal yield and the like, and is difficult to meet the requirements of industrial production on high-efficiency and low-cost preparation of high-purity crystals. Therefore, the S-equol monocrystal with high purity, good stability and no solvent residue is developed, a simple and feasible preparation method and an accurate configuration determination scheme are established, and the S-equol monocrystal has important significance for promoting the industrialized application of the S-equol and improving the quality and the drug effect of related products and is also a technical problem to be solved in the current field. Disclosure of Invention The invention aims to solve the problems of solvent co-crystallization, undefined crystal form, low configuration determination precision, complex preparation process and the like of S-equol in the prior art, provides an S-equol monocrystal with clear crystal system and unit cell parameters and high purity, and simultaneously provides a simple and efficient preparation method and a precise configuration determination scheme so as to meet the industrial application requirements. In order to achieve the purpose, the technical scheme adopted by the invention is that the S-equol single crystal is characterized in that the single crystal is composed of pure S-equol molecules, is not co-crystallized with solvent molecules, belongs to an orthorhombic system and has a space group of P212121. Further, the single crystal has unit cell parameters of a= 9.225 a, b= 9.449 a, c= 13.055 a, α=β=γ=90°. Further, the R factor of the single crystal is 0.0336-0.0331. Further, the single crystal is in a cluster or grain shape and has an asymmetric crystal shape. A process for preparing S-equol monocrystal includes such steps as dissolving S-equol in absolute alcohol to obtain a solution, putting it in container, and naturally volatilizing solvent at room temp. Further, wherein the amount of S-equol is 20mg and the amount of absolute ethanol is 0.8mL. Further, the container is a quartz cuvette. Further, the inner diameter of the quartz tube was 5mm. A method for determining the absolute configuration of S-equol, comprising obtaining the S-equol single crystal of any one of claims 1-4, determining the crystal structure of the single crystal using a single crystal X-ray d