Synthesis of Novel 17-Oxo-17a-Aza-D-Homo-3, 5-Seco-Steroids as Potential 5α-Reductase Inhibitors


University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India


Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate gland. It
is a leading disorder of the elderly male population. Excessive production of dihydrotestosterone
has been implicated in this pathological condition. Steroidal 5α-reductase is a membrane bound
NADPH dependent enzyme which is responsible for the conversion of testosterone (T) to
dihydrotestosterone (DHT). Therefore, inhibition of production of DHT by 5α-reductase
inhibitors is an important approach for the treatment of BPH. The proposed 17-oxo-17a-aza-Dhomo-
3,5-seco-steroids (17-20) have been synthesized using diosgenin as the starting material.
Diosgenin was converted to 17-oxo-3, 5-seco-4-nor-androstan-3-oic acid following six steps:
Oppenauer oxidation, Lemieux-von Rudloff oxidation, Wolff-Kishner reduction, Marker
degradation, oximation and Beckmann rearrangement. 17-Oxo-3, 5- seco-keto acid was then
converted to 17-oxo-17a-aza-D-homo-3, 5-seco-4-nor-androstan-3-oic acid by oximation
followed by Beckmann rearrangement. The resulted seco-keto acid was then treated with thionyl
chloride and the respective amines and phenols to get the desired 3, 5-seco-steroidal amides (17-
18) and esters (19-20) respectively.


[1] T.L. Bullock, G.L. Andriole, Expert Opin. Emerg. Drugs 11 (2006) 111-123.
[2] G. Andriole, N. Bruchovsky, L.W. Chung, A. M. Matsumoto, R. Rittmaster, C. Roehrborn, D.
Russell, D. Tindall, J. Urol. 172 (2004) 1399-1403.
[3] S.A. Kaplan, Urology 58 (2001) 65-70.
[4] A. Kurup, R. Garg, C. Hansch, Chem. Rev. 100 (2000) 909-924.
[5] P. Sanchez, J.M. Torres, E. Ortega, Neurochem. Res. 30 (2005) 577-581.
[6] F.C. Lowe, J.D. McConnell, P.B. Hudson, N.A. Romas, R. Boake, M. Lieber, M. Elhilali, J. Geller, J.
Imperto-McGinely, G. Andriole, R.C. Bruskewitz, P.C. Walsh, G. Bartsch, J.N. Nacey, S. Shah, F.
Pappas, A. Ko, T. Cook, E. Stoner, J. Waldstreicher, Urology 61 (2003) 791-796.
[7] B. Djavan, S. Milani, Y.K. Fong, Expert Opin. Pharma. 6 (2005) 311-317.
[8] N.A. Zerhouni, M. Maes, C. Sultan, S. Rothwell, C.J. Mlgeon, Steroids 33 (1979) 277-285.
[9] M. Cabeza, I. Heuze, E. Bratoeff, E. Murillo, E. Ramirez, A. Lira, Chem. Pharm. Bull. 49 (2001)
[10] H. Singh, R.K. Gupta, T.R. Bhardwaj, Indian J. Chem. 27B (1988) 508-512.
[11] R.E. Marker, T. Tsukamoto, D.L. Turner, J. Am. Chem. Soc. 62 (1940) 2525-2531.
[12] H. Singh, P.P. Sharma, R.B. Mathur, Indian J. Chem. 11 (1973) 1254-1256.
[13] R.U. Lemieux, E.V. Rudloff, Can. J. Chem. 33 (1955) 1701-1709.
[14] E.V. Rudloff, Can .J. Chem. 43 (1965) 1784-1791.
[15] R.E. Marker, H. Rohrmann, J. Am. Chem. Soc. 61 (1939) 3592-3593.
[16] R.E. Marker, E. Rohrmann, J. Am. Chem. Soc. 62 (1940) 518-520.
[17] G.H. Posner, B.A. Halford, S. Peleg, P. Dolan, T.W. Kensler, J. Med. Chem. 45 (2002) 1723-1730.
[18] M. Kumar, A.K. Rungta, T.R .Bhardwaj, H. Singh, Indian J. Chem. 29B (1990) 611-614.
[19] A. Kasal, Collect. Czech. Chem. Commun. 45 (1980) 2541-2549.
[20] E.B. Hershberg, J. Org. Chem.13 (1948) 542-546.
[21] M.R. Yadav, M.M. Ganesh, R .Giridhar, M. Kumar, Asian J. Chem. 16 (2004) 1027-1033.
[22] C.A.G.N. Montalbetti, V. Falque, Tetrahedron 61 (2005) 10827-10852.