Synthesis and characterization of new aromatic esters based on 4,16-pregnadiene-6,20-dione skeleton

Studies on steroids stimulated renewed interest because apart from their estrogenic and anabolic/androgenic activity [1-3] steroids were found to show various biological activities including cytotoxicity [4], antiproliferative activity [5], antimicrobial activity [6], anti-glioma activity [7], inhibition of cholesterol α-glucosyltransferase [8], neuromuscular blocking activity [9], differential activities on prostate cancer cells [10], anti-osteoporosis activity [11], and anti-aging activity [12]. Up until now steroids have showed potential applications as 5α-reductase inhibitors [13], as modulators of inflammation and immunity [14], as inhibitors of 17α-hydroxylase/C17,20-lyase [15], as predictor of tamoxifen response in premenopausal breast cancer [16], as progesterone receptor antagonist [17], as glucocorticoid receptor imaging agents [18], as inhibitors of protein tyrosine phosphatase 1B [19], as reversal agents of multidrug resistance in cancer cells [20], as inhibitors of 17β-hydroxysteroid dehydrogenase [21], and as ligands for drug vectors [22]. Some steroidal compounds were used for photodynamic therapy [23], for cancer chemotherapy [24], and for DNA delivery [25]. Moreover, cholesteric liquid crystal [26] and steroid-based organogelator [27] were also studied. Recently Cabeza and collegues synthesized a series of 3β-benzoyloxy-4,16-pregnadiene-6,20-dione (1a-e, Figure 1) and 3β- cycloalkylcarbonyloxy-4,16-pregnadiene-6,20-dione (2a-d, Figure 1) compounds starting from 16-dehydropregnenolone acetate (16-DPA) and evaluated their biological activities. Of these steroids 1a is a good inhibitor for the 5α-reductase enzyme [13] while 1b-e and 2a-d showed high antiandrogenic activity [28,29]. In continuation of our study on steroids [30,31] and to explore an improved way for synthesis of new steroidal compounds from the cheap starting material diosgenin, herein we report the synthesis and structural characterization of a series of new aromatic esters based on 4,1