The Study On The Microbial Manufacture Of 3-one-4-ene-steroids By Mucor Racemosus And Synthesis Of Dehydroepian Drosterone (DHEA) And 3β-phosphate-DHEA.

A general review on status of steroidal drugs industry, development of steroidal drugs new resources, application of microbes transformation to steroidal drugs transformation, and R&D of steroids hydroxylation by microorganism was given in this dissertation. Work on the following four aspects are carried out accordingly.1. The Microbial manufacture of 4-ene-3-oxosteroids by Mucor racemosus With the previous work on Mucor racemosus in our Lab, transformation of compound 1 and 4 by Mucor racemosus was further studied. Biotransformation products were isolated, purified and determined. The reaction formulas are:Scheme 12. The effects of medium composition and environment on the hydyoxylation reaction of Mucor racemosus.The optimal culture medium composition was obtained through employing single factor. It is as following: glucose 1.5%, yeast extraction0.1%, KH2PO41.3%, and peptone 1.2%, the inoculum amount 20%, medium's initial pH 4.5.3. The synthesis of dehydroepiandrosterone (DHEA)DHEA is an important intermediate for synthesis of norpregneninolone , ethinylestradio land methyl testosterone, etc. The starting material used in our synthesis was natural diosgenin, which is very cheap and easily obtained. Diosgenin went through a 3-step reaction path which includes: ring-opening, oxidation andhydrolysis. The yield for diene product was 80%. DHEA was then synthesized using these diene product.Scheme 2 4. Sythesis of dehydroepiandrosterone 3 β -phosphateIn order to further investigate the relation of the steroid phosphate esters' structures, property and bioactivity, dehydroepiandrosterone 3 β -phosphate wassynthesized with POCl3 as phosphated reagent. The synthesis reaction is:Scheme 3...