## Materials and Methods
### Synthetic Procedures
#### 2.2.2 Synthesis of 16-Cyano-3\(\beta\)-Hydroxy-Androst-5-en-17-One (**3**)
5\({}^{\prime}\)-Amino-1\({}^{\prime}\)-4\"-Tolylypyrazole[3\({}^{\prime}\),\({}^{\prime}\):17,16]Androst-5-en-3\(\beta\)-ol (6b)  
4-Tolyhydrazine hydrochloride (5b, 119 mg) was used as described in the general procedure. Yield: 186 mg (89\(\%\), white solid); Mp 267-269 \({}^{\circ}\)C; \(R_{\rm f}\) = 0.26 (EtOAc/CH\({}_{2}\)Cl\({}_{2}\) = 20:80 \(v\)/\(v\)). Anal. Calcd. for C\({}_{27}\)H\({}_{35}\)N\({}_{3}\)O (417.60): C, 77.66; H, 8.45. Found: C, 77.47; H, 8.32. \({}^{1}\)H NMR (DMSO-\(d_{6}\), 500 MHz): \(\delta\) 0.95 (s, 3H, 18-H\({}_{3}\)), 1.01 (s, 3H, 19-H\({}_{3}\) and m, 2H), 1.37 (m, 1H), 1.49-1.80 (overlapping m, 8H), 1.98-2.19 (overlapping m, 5H), 2.31 (s, 3H, 4\"-CH\({}_{3}\)), 2.40 (dd, 1H, \(J\) = 13.3 Hz, \(J\) = 4.7 Hz, one of 15-H\({}_{2}\)), 3.27 (m, 1H, 3-H), 4.62 (d, 1H, \(J\) = 4.5 Hz, 3-OH), 5.03 (s, 2H, 5'-NH\({}_{2}\)), 5.32 (d, 1H, \(J\) = 4.1 Hz, 6-H), 7.21 (d, 2H, \(J\) = 8.2 Hz, 3\"-H and 5\"-H), 7.40 (d, 2H, \(J\) = 8.2 Hz, 2\"-H and 6\"-H); \({}^{13}\)C NMR (DMSO-\(d_{6}\), 125 MHz): \(\delta\) 18.0 (C-18), 19.1 (C-19), 20.2 (CH\({}_{2}\)), 20.5 (4\"-CH\({}_{3}\)), 23.6 (CH\({}_{2}\)), 30.4 (CH), 30.9 (CH\({}_{2}\)), 31.5 (CH\({}_{2}\)), 33.6 (CH\({}_{2}\)), 36.4 (C-10), 36.9 (CH\4-Methoxy-phenylhydrazine hydrochloride (5**c**, 131 mg) was used as described in the general procedure. Yield: 199 mg (92%, white solid); Mp 209-211 \({}^{\circ}\)C; \(R_{\rm f}\) = 0.17 (EtOAc/CH\({}_{2}\)Cl\({}_{2}\) = 20:80 _v_/_v_). Anal. Calcd. for C\({}_{2}\)H\({}_{35}\)N\({}_{3}\)O\({}_{2}\) (433.60): C, 74.79; H, 8.14. Found: C, 74.65; H, 8.02. \({}^{1}\)H NMR (DMSO-\(d_{6}\), 500 MHz): \(\delta\) 0.95 (s, 3H, 18-H\({}_{3}\)), 1.01 (s, 3H, 19-H\({}_{3}\) and m, 2H), 1.37 (m, 1H), 1.49-1.80 (overlapping m, 8H), 1.97-2.20 (overlapping m, 5H), 2.40 (dd, 1H, \(J\) = 13.2 Hz, \(J\) = 4.7 Hz, one of 15-H\({}_{2}\)), 3.27 (m, 1H, 3-H), 3.77 (s, 3H, 4\"-OMe), 4.63 (d, 1H, \(J\) = 4.5 Hz, 3-OH), 4.96 (s, 2H, 5\"-NH\({}_{2}\)), 5.32 (m, 1H, 6-H), 6.96 (d, 2H, \(J\) = 9.0 Hz, 3\"-H and 5\"-H), 3\"-H and 5\"-H), 7.40 (d, 2H, \(J\) = 9.0 Hz, 2\"-H and 6\"-H); \({}^{13}\)C NMR (DMSO-\(d_{6}\), 125 MHz): \(\delta\) 18.1 (C-18), 19.1 (C-19), 20.2 (CH\({}_{2}\)), 23.6 (CH\({}_{2}\)), 30.4 (CH), 30.9 (CH\({}_{2}\)), 31.5 (CH\({}_{2}\)), 33.6 (CH\({}_{2}\)), 36.4 (C-10), 36.9 (CH\({}_{2}\)), 40.2 (C-13), 42.3 (CH\({}_{2}\)), 50.1 (CH), 55.3 (4\"-OMe), 61.3 (CH), 70.0 (C-3), 103.4 (C-16), 114.0 (2C, C-2\" and C-6\"), 120.2 (C-6), 124.4 (2C, C-3\" and C-5\"), 133.4 (C-1\"), 140.4 (C-5), 141.6 (C-5\"), 156.9 (C-4\"), 167.8 (C-17); ESI-MS 434 [M + H]\({}^{+}\). 5\({}^{\prime}\)-Amino-1\({}^{\prime}\)-(4\"-Fluoro)phenylpyrazol[3\({}^{\prime}\),\({}^{\prime}\)4\({}^{\prime}\):17,16]Androst-5-en-3\(\beta\)-ol (**6d**)  
4-Fluoro-phenylhydrazine hydrochloride (**5d**, 122 mg) was used as described in the general procedure. Yield: 198 mg (94%, white solid); Mp 278-280 \({}^{\circ}\)C; \(R_{\rm f}\) = 0.35 (EtOAc/CH\({}_{2}\)Cl\({}_{2}\) = 20:80 _v_/_v_). Anal. Calcd. for C\({}_{26}\)H\({}_{32}\)FN\({}_{3}\)O (421.56): C, 74.08; H, 7.65. Found: C, 73.95; H, 8.73.