Research About Modified On D-ring Of Glucocorticoids

It was well known that glucocorticoids, required drugs in the drugstore, are important part of steroids and are used widely in the therapy of many diseases such as antiinflammation. It was found that D-ring played an important effect in the glucocorticoid drugs after glucocorticoid receptor and current glucocorticoid drugs were reviewed. Just because of this important effect of D-ring, modified on D-ring was a pop topic all through studies about glucocorticoid drugs in this forty years. However, the synthesis of D-homoglucocorticoids, a candidate maybe make a new region for the application of glucocorticoids, and 16α, 17α-dimethylglucocorticoids, the safest glucocorticoid drugs such as rimexolone, was very difficult. In order to promote the reaearch about structure & activity relationship and pharmacology of these kinds of drugs, this difficulty of synthesis must be solved. Our thesis, research about mortified on D-ring glucocorticoids, appeared just under this background. Meanwhile, emphases of our research were chosed purposefully on methods of synthesis of D-homoglucocorticoids and 16α, 17α-dimethylglucocorticoidsFirstly, Intermediates that have the structure of 16 (17)-20-one were prepared through prednisolone and ADD (androsta-1,4-diene-3, 17-dione). Then, D-homoglucocorticoids were prepared smoothly through 1,3-dipolar reaction, decomposition of methyleneazopregnanes and expanding of D-ring (showed in followed scheme). The experimental results showed that this synthesized process had highly regio- and stereoselective and this phenomenon appeared especially during the translation of 16α,17α-miethyleneazopregnanes to 16α,17α-methylenepregnanes. The farther...