Syntheses Of Galeterone For Treatment Of Castration-Resistant Prostate Cancer

Prostate cancer,one of the malignant cancer and a serious threat to men’s health,has drained millions of men’s lives around the world.Androgen and androgen receptors play an important role in prostate cancer since androgen is the main energy for the growth of prostate cancer and most prostate cancers depend on androgen in their initial growth.Therefore,androgen inhibiting therapy can be applied to treat various stages of prostate cancer.For the early stage of prostate cancer,androgen deprivation therapy(ADT)could decrease the level of androgen inside patients.However,castration treatment can not entirely suppress the development of prostate cancer,and disease progression become castration resistant prostate cancer(CRPC)after 14-30 months.Galeterone developed by Tokai Pharmaceuticals,Inc that disrupts the growth and survival of cancer cells via a novel and proprietary triple mechanism of action.Galeterone follows androgen receptor(AR)directed therapy that suppress the body’s synthesis of male hormones.In vivo,cytochrome oxidase(CYP17)composite catalytic convert androgen steroids,which is the cytochrome P450 family one by 17α-hydroxylase and 17,20-lyase composition.Because CYP17 is expressed in the testis,adrenal gland,normal prostate tissue and prostate cancer cells,so inhibiting cytochrome oxidase(CYP17)can treat castration-resistant prostate cancer(CRPC).In this paper,we first optimize the synthetic route of Galeterone which had four steps with DHEA acetate as the starting material.The first step is Vilsmeier-Haack reaction.The product is substituted 17-cloride with benimidazole,and then deformylated by 10% Palladium carbon and lastly hydrolyze the ester.We then design a new synthetic route of Galeterone by forming C—N bond.Using Dehydroepiandrosterone as the starting material to get the vinyl iodide intermediate,which is then reacted with benimidazole under cuprous iodide catalyzed,we successfully provide a low cost,high-yielding and simple process synthesis method with easy operation.