Syntheses Of Abiraterone Acetate And Galeterone

Prostate cancer is a common malignant tumor of the male reproductive system.Abiraterone acetate and Galeterone are both used for the treatment ofcastration-resistant prostate cancer (CRPC). The main purpose of this paper is tostudy and optimize the reported synthetic routes of the two drugs, and explore newsynthetic routes.Abiraterone acetate (Zytiga) was approved on the market by FDA in2011.According to the references, we firstly studied and improved the two synthetic routesas follows:1. Abiraterone acetate was synthesized from dehydroepiandrosteroneacetate via enol esterification and Suzuki coupling with an overall yield of72%.2.Abiraterone acetate can also be prepared starting from dehydroepiandrosterone viathe formation of hydrazone, vinyl iodide, the Suzuki coupling and acetylation with anoverall yield of47%.Then, we studied Suzuki coupling reaction, the key step of the the two syntheticroutes, and replaced the nucleophile and electrophile of the reaction. We found that itwas better when3-pyridine boronic acid and17-bromoandrosta-5,16-diene-3β-olwere used as reaction substrates.Finally, we designed and studied a new route for the synthesis of abirateroneacetate by organometallic reagents (organozinc reagents, organomagnesium reagents).This method is simple and the yield is fine.Galeterone (TOK-001), produced by Tokai Pharmaceuticals, is in a phase IIclinical trial. It is used for the treament of castration-resistant prostate cancer viatriple mechanism of action. According to the references, we firstly studied andoptimized the synthetic route. Galeterone can be synthesized fromdehydroepiandrosterone acetate via Vilsmeier-Haack reaction, nucleophilicsubstitution, decarbonylation and ester hydrolysis with an overall yield of43%.Then, we designed a new route for the synthesis of galeterone bycopper-catalyzed cross-coupling, and explored some reaction conditions.