Crystal Stucture of 17-β-Benzoyloxy-16-β-methylpregna-4,6-diene-3,20-dione

and the second leading cause of cancer deaths in North American men. Androgen antagonists offer a potentially useful treatment for androgen-mediated diseases, such as: prostatic cancer, hirsutism, acne, seborrhea, androgenic alopecia and benign prostatic hyperplasia.1 Although surgery presently represents an alternative treatment for prostatic cancer, there are several modalities available.2 Currently, the most common therapy for the treatment of androgen-dependent diseases is blockage of the androgen receptors by androgen antagonists3, or inhibition of the conversion of testosterone to the more active androgen dihydrotestosterone by the enzyme 5α-reductase.4 In this paper we describe the synthesis and the X-ray structure determination of a new antiandrogen, 17-βBenzoyloxy-16-β-methylpregna-4,6-diene-3,20-dione, 8. All of the steps involved in this synthesis are wellknown reactions5, and the preparation of 8 is summarized in Scheme 1. In this synthesis, the most intriguing step is the transformation of 7 to the benzoate ester 8, which occurs with an inversion of the configuration of the ester moiety. Probably, the bulky ester chain at C17 effects the conformation of the ring D, and acquires a β configuration. The X-ray data were collected by a graphite-monochromatized Mo Kα radiation. No absorption correction was applied. Table 1 summarizes the crystal and experimental data. The molecular structure of the title compound is shown in Fig. 1. The molecule consists of three six-membered rings and one five-membered ring, all trans fused. For the puckering-parameters values (φ2, θ2 and Q), the sixmembered rings (A and B) both occur in a distorted envelope conformation, while ring C and D(φ2 and Q) occur in a distorted chair and a half chair conforma197 ANALYTICAL SCIENCES FEBRUARY 1999, VOL. 15