Synthesis of the Abiraterone Derivatives 5α- and 5β-Δ(1)-Abiraterone and Structural Determination of an Unknown Metabolite in Human Serum Derived from Oral Abiraterone Acetate

阿比特龙衍生物5α-和5β-Δ(1)-阿比特龙的合成及口服阿比特龙醋酸酯在人血清中未知代谢物的结构鉴定

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Abstract

Abiraterone (Abi) acetate, an anticancer drug, produces metabolites in the serum of patients with prostate cancer. Three unknown metabolites of Abi are previously discovered and the structures of two of these compounds are determined by comparing their LC-based retention times with those of synthesized compounds. However, the structure of the third metabolite is not identified. Herein, two new Abi derivatives, 5α-Δ(1)-abiraterone (5α-D1A) and 5β-Δ(1)-abiraterone (5β-D1A), with a molecular weight of 348, are successfully synthesized as candidates for the third unknown metabolite. 5β-D1A is confirmed as this third metabolite based on its retention time in the extracted ion chromatogram. The metabolic pathway may have formed 5β-D1A rather than 5α-D1A because of the higher activity of steroid 5β-reductase compared with that of 5α-reductase. These findings are expected to lead to the discovery of new metabolic pathways.

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