The Study Of Micro-conversion Of Prednisolone

Prednisolone (11β,17α,21-Trihydroxy pregnane-1,4-diene-3,20-ketone)is animportant steroid compound, take prednisone as material can obtain triamcinolone、budesonide、ciclesonide、desonide by chemosynthesis methods, which four kinds ofdruggery are the main medicament to cure asthma hold huge market potential. But theabove-mentioned methods of chemosynthesis all have the defects of complicatedprocesses、more byproducts、high cost and so on, bring inconvenience to industrializationproduction, so the study of micro-conversion of prednisolone is quite necessary.This paper select four kinds of streptomyces as the main transfer epiphyte, studythe ability of transformation、micro-conversion technics of prednisone and methods ofseparation and purification. The main contents and results are as follows：1. Ascertain the absorption wavelength is245nm by ultraviolet absorption detector,optimize the TLC and HPLC conditions by the out of peak time of the substrate andproduct, assure the qualitative and quantitative analysis methods.2. Take strain WM-3and WM-4as initiative epiphyte, obtain the same transferproduct WMFP. Consider WM-4as study object, see the conditions such as carbon andnitrogen resources、inoculate time、concentration of substrate、time of substrate addingand other conditions to the conversion. The result shows that the seeds arrive atlogarithmic phase in24hours, then add substrate into the ferment can reject the resistancesubstrate to the stain, when substrate thickness is2.5mg/mL,add it in24h, take ethanol ascosolvent and combine physical and chemical mutagenesis, the conversion can reachabove70%. Extract and purify WMFP by column chromatography, confirm the structureis11β,17α,20,21-Tetrahydroxy pregnane-1,4-diene-3-ketone, the molecular weight is362. The structure is identified by MS and NMR.3. Take WM-1and WM-2as initiative epiphyte, both the final products are16α-prednisone and WMPF. Consider WM-1as study object, see the conditions such ascarbon and nitrogen resources、inoculate time、concentration of substrate、time of substrate adding and other conditions to the conversion. The result shows the thickness ofsubstrate is2mg/mL, add substrate after26h, consider PEG as cosolvent and combinewith mutagens, the output of16α-prednisone can reach5%.4. The method of take prednisone as material after micro-conversion course toobtain WMFP hasn’t been reported before.