Highly efficient nucleophilic addition of alkyl Grignard reagents to 17-ketosteroids in the presence of cerium(III) chloride: Synthesis of 17α-propyl-17β-hydroxy-4-androsten-3-one, an androgen receptor antagonist

The study from 1994 demonstrated that the use of anhydrous cerium(III) chloride significantly improved the nucleophilic addition of alkyl Grignard reagents to 17-ketosteroids, yielding high amounts and high stereoselectivity of the addition products. This method was notably effective in synthesizing 17α-propyl-17β-hydroxy-4-androsten-3-one, a compound with potential as an androgen receptor antagonist for treating conditions such as benign prostatic hyperplasia, prostatic cancer, and androgenic alopecia. The RMgX-Ce(III)Cl3 complex facilitated the efficient introduction of alkyl chains at the 17α-position of 17-ketosteroids, overcoming previous challenges in preparing these compounds for biological evaluation. For instance, the addition of n-BuMgCl-Ce(III)Cl3 complex to 17-ketosteroids resulted in a 91% yield of the addition product, and the synthesis of 17α-propyltestosterone was achieved with excellent yield and high stereoselectivity. The research was funded by Endorecherche and offered a novel method for synthesizing steroidal compounds with targeted biological activities.