Synthesis on Progesterone Using Stigmasterol as Starting Material

Progesterone was synthesized within 3 steps reactions by employing stigmasterol as starting material. Firstly, Stigmasta-4, 22(E)-3-diene ketone (compound 1) was obtained by Oppenauer oxidation, and the result demonstrated that the oxidation is quite complete with the yield of 95.0%. Secondly, stigmast-4-ene-3-one-21-aldehyde (compound 2) was synthesized by ozonation with the yield of 94.5%. Thirdly, the he reaction is another ozonation and it is the key step for progesterone synthesis. The some exploration for the reaction was carried out, and these experiments show that if via the enamine formation and then oxidation to provide progesterone, this method suffer from quite low yield, and there is little production value. When employing acetic anhydride for acylating compound 2 to give the corresponding esters. LC-MS proved the esters mainly consists of two compounds. Without separation and purification the esters can be used for the next ozonation, and the reaction mixture was worked up by means of reductive hydrolysis, acidification, recrystallization to give progesterone with the yield of 43.4%. The total yield is 39.0% from stigmasterol. This process is a practical route for production of progesterone with high value-added from unexpensive raw material stigmasterol.