| Budesonide, 16α,17α-acetal of pregnane derivative, was a glucocorticoid withouthalogen. Budesonide had a high ratio of topical-to-systemic activity and was used forthe treatment of asthma widely. There were two diastereoisomers of Budesonide dueto the C22 chiral center, but the pharmacological activity of the two diastereoisomerswas quite different. The stereoselectivity of C<sub>22 of Budesonide was investigated in thispaper. Budesonide was synthesized from different materials and the ratio of thediastereoisomers were determined by HPLC and CE. The main work was described asfollowing:Budesonide was obtained from the hydrolysis of 21-OAc budesonide, which wasobtained by the acetalizaton of 21-OAc-16α-hydroxyprednisolone withn-butyraldehyde. When the molar ratio between 21-OAc-16α-hydroxyprednisoloneand n-butyraldehyde was 1:2.5 and the concentration of21-OAc-16α-hydroxyprednisolone was 0.05g/mL (solvent), a 85% yield of a productcontaining 22R to 22S as 40:60 was obtained.16α-hydroxyprednisolone was obtained in a 97% yield by the hydrolysis of21-OAc-16α-hydroxyprednisolone in base.Acetalizaton of 16α-hydroxyprednisolone with n-butyraldehyde was catalyzed byperchloric acid with the molar ratio between 16α-hydroxyprednisolone and perchloricacid as 1:4. At room temperature for 3h, a 96% yield of a product containing 22R to22S as 85:15 was obtained.Acetalizaton of 16α-hydroxyprednisolone with n-butyraldehyde was promoted bymicrowave irradiation for 60s and budesonide was obtained in a 91% yield with 22Rto 22S as 75:25.Budesonide was obtained by the transketalization reaction of desonide with a95% yield of a product containing 22R to 22S as 70:30.The separation of 22R/22S-budesonide was studied in this paper. Compared tothe 22R/22S diastereoisomers of budesonide which can be separated by HPLC, thediastereoisomers of 21-OAc budesonide should be determined by CE.
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