Crystal Structure and Synthesis of Three New Steroidal Derivatives as Antiandrogens

AbstractThe structures of 3β-cyclobutyl carbonyloxy-5-androsten-17-one (C 24 H 34 O 3 ), compound 1; 3β-cyclopentyl carbonyloxy-5-androsten-17-one (C 25 H 36 O 3 ), compound 2; and 3β-cyclohexyl carbonyloxy-5-androsten-17-one (C 26 H 38 O 3 ) compound 3 were established by spectral and X-ray diffraction studies. Steroidal derivatives 1-3 exhibited a high antiandrogenic effect and could be considered as potential drugs for the treatment of prostate cancer. Compound 1 crystallizes in the orthorhombic space group P2 1 2 1 2 1 with unit cell parameters a = 6.618(2), β = 14.167(3), c = 22.329(5) A, Z = 4. Compound 2 crystallizes in the orthorhombic space group P2 1 2 1 2 1 with unit cell parameters a = 6.631(2), b = 13.865(4), c = 23.952(7) A, Z = 4. Compound 3 crystallizes in the orthorhombic space group P2 1 2 1 2 1 with unit cell parameters a = 6.6100(9), b = 13.896(2), c = 24.491(3) A, Z = 4. All three structures (1-3) were solved by direct methods and refined to R = 0.0708, 0.0750 and 0.0496, respectively. For compound 2, there is positional disorder of the side chain at C3. All the rings of both steroid skeletons are trans connected. For structures 1-3, the six-membered rings A, B and C have a deformed chair, half chair and deformed chair conformations. The five-membered rings D adopt an intermediate envelope and half-chair conformations. For structure 2, the five-membered rings E and EA have a deformed envelope and an intermediate envelope and half-chair conformations, respectively. For structure 3, the six-membered ring E adopts a deformed chair conformation. Cohesion of the crystals can be attributed to van der Waals and weak C-H⋯O interactions.Index AbstractThe crystal structures of three new steroidal derivatives as antiandrogens and their conformation were obtained by X-ray diffraction techniques from suitable single crystals. Steroidal derivatives 1-3 exhibited a high antiandrogenic effect and could be considered as potential drugs for the treatment of prostate cancer.[IMAGE]