Drospirenone Synthesis

Drospirenone, as a new generation of oral contraceptive, developed by Shering Corporation in Germany is a new type synthetic progesterone endowed with anti-mineralocorticoid and antiandrogen activities simultaneously instead of activities of androgen, estrogen, glucocorticoid and anti-glucocorticoid and with a pharmacological action spectrum similar to that of natural progesterone. Yasmin, as a combination oral contraceptive, composed of drospirenone and aethinyloestradiol is a safe and effective low-dose oral contraceptive with good tolerance. Angeliq, 0.5mg drospirenone/1mg estradiol combined agent, is used for treating menolipsis and preventing osteoporosis for the first time in Holland at the end of 2002 and used for treating moderate and severe vasomotion in 2005 approved by FDA in the US. Now, the combined agent containing drospirenone has come into markets of many countries.Based on reported drospirenone synthetic routes in literatures, the paper divides the target compound synthesis into three parts by using chemical synthesis method instead of microbial fermentation method. Through studying the synthetic route of each part, an synthetic method with improved stereoselectivity can be realized industrialization is established by selecting epiandrosterone acetate as raw material and subjecting to 16 reaction steps. The method in the paper can be developed further.