The Utility Of Natural Sterols

Androsta-1,4-dien-3,17-dione(ADD) was obtained from the degradation of natural sterols by microorganisms in good yield. Using this important starting material, we have done two parts of research as follows:1. Synthesis of 2-methoxyestradiol2-Methoxyestradiol has been demonstrated to act as an antiangiogenic agent that prevents the growth of new blood vessels required to nourish tumors. It can provide significant advantages over multiple myeloma, prostate cancer, breast cancer etc. and has a broad-spectrum antitumor activity. Our research group has already completed the synthesis and industrialization of estradiol from ADD. This work is using estradiol as starting material to synthesize 2-methoxyestradiol. We improved the synthetic method by omitting two reaction stages compared with reported method and the target compound was confirmed via spectra.2. Study on some key points for converting ADD to highly active glucocorticoidsSynthesis of the highly active glucocorticoids with 1,4-dien-3-one system with ADD as the starting material, has attracted the attention of many organic synthetic chemists since 1970's. However, a practical synthetic method for scale production has not been acquired. A few reports are just using uncommon reagents and conditions to finish the conversion from ADD to highly active glucocorticoids in laboratory. These methods are restricted and difficult to apply in scale manufacturing. In our project, we want to explore a convenient, practical, mild route toward highly active glucocorticoids from ADD and three key difficulties have been resolved:(1) Introduction of 11-oxygen functional group of ADD;(2) The high stereoselective introduction of 17β-two carbon side chain at 17-keto ofΔ^1,4 -steroids and a concise conversation to Δ¹⁶-20-one system; (3) Protection and deprotection of the C-3 carbonyl group in the ring A 1,4-dien-3-onegroup.Moreover, the details and key influential factors of each reaction are carefully investigated. All reagents used in the synthetic procedure are easily prepared or available. The synthesis of pregna-1,4,9(11),16-tetraen-3,20-dione, a key precursor for synthesizing a series of highly active glucocorticoids with 1,4-dien-3-one system, was completed. Experiment demonstrates that this route is economic, practical and potential for scale production. This study also makes a useful contribution to steroid chemistry by providing a new synthetic methodology for protection and deprotection of the C-3 carbonyl group in the ubiquitous and sensitive ring A 1,4-dien-3-one moity. Because a lot of sterols could be obtained from some industrial waste, the synthesis of valuable steroidal drugs based on this natural resource has great economic and scientific significance.