A new simple and high-yield synthesis of 5α-dihydrotestosterone (DHT), a potent androgen receptor agonist

Steroids

Volumn 77, Issue 14, 2012, Pages 1530-1534

  Purushottamachar, Puranik ^a   Njar, Vincent C O ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

5 Dihydrotestosterone (DHT); Androgen receptor (AR); Improved synthetic procedure; Prostate cancer (PC)

Indexed keywords

17BETA [TERT BUTYLDIMETHYLSILYL)OXY] 5ALPHA ANDROSTAN 3 ONE; ANDROSTANOLONE; EPIANDROSTERONE; UNCLASSIFIED DRUG;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CHROMATOGRAPHY; DEPROTECTION REACTION; DRUG SYNTHESIS; INFRARED SPECTROSCOPY; JONES OXIDATION; PROTON NUCLEAR MAGNETIC RESONANCE;

ANDROGENS; ANDROSTERONE; CYCLIC N-OXIDES; DIHYDROTESTOSTERONE; MORPHOLINES; OXIDATION-REDUCTION;

EID: 84868222656     PISSN: 0039128X     EISSN: 18785867     Source Type: Journal    
DOI: 10.1016/j.steroids.2012.09.003     Document Type: Article

References (32)

1. D.W. Russell The enzymes, regulation, and genetics of bile acid synthesis Annu Rev Biochem 72 2003 137 174
2. D.W. Russell, and J.D. Wilson Steroid 5 alpha-reductase: two genes/two enzymes Annu Rev Biochem 63 1994 25 61
3. A. Cilotti, G. Danza, and M. Serio Clinical application of 5alpha-reductase inhibitors J Endocrinol Invest 24 2001 199 203
4. T. Saartok, E. Dahlberg, and J.A. Gustafsson Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin Endocrinology 114 1984 2100 2106
5. M. Donike, M. Ueki, Y. Kuroda, H. Geyer, E. Nolteernsting, and S. Rauth Detection of dihydrotestosterone (DHT) doping: alterations in the steroid profile and reference ranges for DHT and its 5 alpha-metabolites J Sports Med Phys Fitness 35 1995 235 250
6. J.P. Salvador, F. Sanchez-Baeza, and M.P. Marco A high-throughput screening (HTS) immunochemical method for the analysis of stanozolol metabolites in cattle urine samples J Chromatogr B 878 2010 243 252
7. Y. Itoh, R. Kitaguchi, M. Ishikawa, M. Naito, and Y. Hashimoto Design, synthesis and biological evaluation of nuclear receptor-degradation inducers Bioorg Med Chem 19 2011 6768 6778
8. J. Roy, R. Breton, C. Martel, F. Labrie, and D. Poirier Chemical synthesis and biological activities of 16a-derivatives of 5a-androstane-3a,17b- diol as antiandrogens Bioorg Med Chem 15 2007 3003 3018
9. J. Roy, P. DeRoy, and D. Poirier 2b-(N-substituted piperazino)-5a- androstane-3a,17b-diols: parallel solid-phase synthesis and antiproliferative activity on human leukemia HL-60 cells J Comb Chem 9 2007 347 358
10. R. Schobert, S. Seibt, K. Effenberger-Neidnicht, C. Underhill, B. Biersack, and G.L. Hammond (Arene)Cl(2)Ru(II) complexes with N-coordinated estrogen and androgen isonicotinates: interaction with sex hormone binding globulin and anticancer activity Steroids 76 2011 393 399
11. D. Thibeault, J. Roy, P. DeRoy, and D. Poirier Chemical synthesis of 2beta-amino-5alpha-androstane-3alpha,17beta-diol N-derivatives and their antiproliferative effect on HL-60 human leukemia cells Bioorg Med Chem 16 2008 5062 5077
12. N.I. Men'shova, G.S. Grinenko, N.A. Korzinkina, and E.P. Frolova Synthesis of 5α-dihydrotestosterone from an intermediate in tigogenin degradation Pharm Chem J 11 1977 1533 1535
13. Ralf W, Sven R, Peter D, Alexander H, Walter E, Birgitt S, et al. Steroid prodrugs with androgenic action. US Patent 2005/0282793 A1.
14. Alberto C, Giuseppe B, Giorgio F, Patrizia F, Mauro G. Aminooxime derivatives of 2- and/or 4-substituted androstanes and androstenes as medicaments for cardiovascular disorders. WO 2009/047101 A1.
15. N.R. Mohamed, G.A. Elmegeed, and M. Younis Studies on organophosphorus compounds VII1 2 Transformation of steroidal ketones with Lawesson's reagent into thioxo and heterofused steroids. Results of antimicrobial and antifungal activity Phosphorus, Sulfur Silicon Relat Elem 178 2003 2003 2017
16. R.D. Bruno, T.S. Vasaitis, L.K. Gediya, P. Purushottamachar, A.M. Godbole, and Z. Ates-Alagoz Synthesis and biological evaluations of putative metabolically stable analogs of VN/124-1 (TOK-001): head to head anti-tumor efficacy evaluation of VN/124-1 (TOK-001) and abiraterone in LAPC-4 human prostate cancer xenograft model Steroids 76 2011 1268 1279
17. P.C. Hartig, K.L. Bobseine, B.H. Britt, M.C. Cardon, C.R. Lambright, and V.S. Wilson Development of two androgen receptor assays using adenoviral transduction of MMTV-luc reporter and/or hAR for endocrine screening Toxicol Sci 66 2002 82 90
18. P. Purushottamachar, A. Khandelwal, T.S. Vasaitis, R.D. Bruno, L.K. Gediya, and V.C. Njar Potent anti-prostate cancer agents derived from a novel androgen receptor down-regulating agent Bioorg Med Chem 16 2008 3519 3529
19. P. Purushottamachar, A. Khandelwal, P. Chopra, N. Maheshwari, L.K. Gediya, and T.S. Vasaitis First pharmacophore-based identification of androgen receptor down-regulating agents: discovery of potent anti-prostate cancer agents Bioorg Med Chem 15 2007 3413 3421
20. M.I. Merlani, L.S. Amiranashvili, N.I. Men'shova, and E.P. Kemertelidze Synthesis of 5a-androstan-3b,17b-diol from tigogenin Chem Nat Compd 43 2007 97 99
21. H. Hosoda, K. Yamashita, H. Sagae, and T. Nambara Studies on dimethyl-tert-butylsilyl ethers of steroids Chem Pharm Bull 23 1975 2118 2122
22. D.M. Spyriounis, G. Ikonomidis, and V.J. Demopoulos A convenient "hydrogen transfer" hydrogenation of testosterone Org Prep Proced Int 21 1989 515 517
23. M.S. Cabeza, E.B. Gutierrez, G.A. Garcia, A.H. Avalos, and M.A. Hernandez Microbial transformations of testosterone to 5alpha-dihydrotestosterone by two species of Penicillium: P. chrysogenum and P. crustosum Steroids 64 1999 379 384
24. M.K. Parr, J. Zapp, M. Becker, G. Opfermann, U. Bartz, and W. Schanzer Steroidal isomers with uniform mass spectra of their per-TMS derivatives: synthesis of 17-hydroxyandrostan-3-ones, androst-1-, and -4-ene-3,17-diols Steroids 72 2007 545 551
25. P.C. Peart, K.P. McCook, F.A. Russell, W.F. Reynolds, and P.B. Reese Hydroxylation of steroids by Fusarium oxysporum, Exophiala jeanselmei and Ceratocystis paradoxa Steroids 76 2011 1317 1330
26. 1 J Org Chem 58 1993 1259 1261
27. V.I. Mel'nikova, and K.K. Pivnitskii Selective reduction of unsaturated ketones by a lithium-ammonia complex Zh Org Khim 8 1972 2090 2098
28. M.M. Hossain, and A.K. Saha Sodium octacarbonylhydridodiferrate. Encyclopedia of reagents for organic synthesis 2001 John Wiley & Sons Ltd.
29. G. Göndös, L.G. McGirr, C.R. Jablonski, W. Snedden, and J.C. Orr The reduction of steroid 2a-fluoro 4-en-3-ones J Org Chem 53 1988 3057 3059
30. 4 activated template polymer J Am Chem Soc 115 1993 2081 2083
31. 5-androstene-3b,17b-diol 17-benzoate hydrogenation products Khim Farm Zh 5 1971 12 14
32. L.N. Volovel'skii, and G.V. Knorozova Synthesis of alkyl derivatives of the androstane series, 2hydroxymethylenedihydrotestosterone and 2a-methyldihydrotestosterone Zh Prikl Khim 35 1962 2580 2582