Studies On The Biosynthesis And Chemical Synthesis Of Intermediates Of The Steroid Drugs And Isosteviol

In this paper, the studies on the microbial transformation and chemical synthesis of the intermediates of steroid drugs and isosteviols have been carried out with biological and chemical methods. The developments of steroids and isosteviol synthesis were also reviewed. Several series of steroidal compounds were prepared from diosgenin which is a readily available commercial product through several chemical steps and one microbial tranformational step and two hydroxylated isosteviol were also prepared from Stevioside. With the steroids and isosteviols as sustrates nearly one hundred strains of fungus were isolated from samples collected from different places of China, and ten strains of fungus have good yields and high selectivity in the biotransformations of steroids and isosteviols. The biotransformal conditions and mechanisms were also dicussed in the paper. Our research work lay a foundation on the further study of steroid drugs and isosteviol.1. A series of important intermediates of steroid drugs were prepared from the commercial diosgenin with chemical methods so as to provide the substrates in following biotransformation step. The derivatives of C19 steroids were obtained in higher yields by the improved synthetic methods.2. Twenty four strains of fungus which could transform steroids were isolated from soil samples after a great deal of screening experiments, of which the eight strains with good yields and high selectivity in the biotransformations were identified as Mucor racemosus, penicillium citreo-viride , Trichoderma viride and Aspergillus according to their morphological characters.3. Nine strains of fungus which could transform isosteviol were isolated from soil samples, of which the two strains have good yields and high selectivity in the biotransformations, and one strain was identified as Rhizopus.4. Mucor racemosus was first used in the microbial transformations of steroids, and their corresponding 7-hydroxylated products were gotten. The favourable biotransformational condition was also confirmed. 5. The biotransformations of a series of steroids by the fungus penicillium citreo-viride A.C.C.C. 0402 have been investigated for the first time, and the conversion to the same product testolactone 38 was observed from compounds 3,1,2 and 5 with the exception of 4,50 and 49. The possible metabolic pathways of the biotransformations were also discussed in the paper.6. The desirous 2-hydroxylated and 4- isosteviol derivetives were gotten in the biotransformations with h-1-2 and Rhizopus for the first time, and compound 108 was the first time to be reported.7. A seris of steroids with amido and aromatic group were synthesized in our work, which may have important bioactivity, and compound 83,84and 86 were the first time to be reported.8. The antitumor activity, imunity activities and glycosidase inhibitory activity of parts of steroid derivatives synthesized above were carried out, and QSAR was also summarized in the paper. The results indicated that some compounds exhibited some strong cytotoxicities on the cell line, and The concentration producing 50% inhibition (IC₅₀) of compound 77 was 0.1338μmol/mL; and compound 77 was convined have some glycosidase inhibitory activity both toαglycosidase andβglycosidase.Our research work will expend the applications of Mucor racemosus, penicillium citreo-viride, Trichoderma viride, Rhizopus and etc, and also provide a new method and compounds for the new steroid drugs screening and sweet compounds, which is of great importance in theory and application.