Article

 

A Convenient Procedure for the Synthesis of 3β-Hydroxy-6-oxo-5α-steroids. Application to the Synthesis of Laxogenin

 

Martín A. Iglesias-Arteaga*^,a, Eva M. Símuta-Lopez^b, Sergio Xochihua-Moreno^b, Omar Viñas-Bravo^b, Sara Montiel Smith^b , Socorro Meza Reyes^b and Jesús Sandoval-Ramírez*^,b

 

^a Departamento de Química Orgánica, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 México - D. F., México. * e-mail: martin.iglesias@servidor.unam.mx.

^b Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, 72570 Puebla - Pue., México. *e-mail: jsandova@siu.buap.mx.

 

Received: June 24, 2004
Published on the web: March 30, 2005

 

Abstract

A convenient pathway to obtain 3β-hydroxy-6-oxo-5α-steroids from 3β-acetoxy Δ⁵-steroids is reported; the methodology was applied to the synthesis of laxogenin (7), substance that behaves as a plant growth hormone. This is an alternative way to produce an important functionality found in many examples of naturally occurring steroids. The developed procedure uses inexpensive reagents and can be carried out in four steps. The oxidizing and acidic steps used in this methodology did not affect the labile spiroketal side chain present in diosgenin (16).

Keywords: laxogenin, diastereoselective epoxidation, 3β-hydroxy-6-oxo-5α-steroids

 

Resumo

Uma rota conveniente para a síntese de 3β-hidroxi-6-oxo-5α-esteroides a partir de Δ⁵-esteroides é descrita tendo sido aplicada para a síntese da laxogenina, substância que apresenta atividade como hormônio de crescimento vegetal. O método é uma alternativa para instalar este grupo funcional importante encontrado em esteróides naturais. O processo descrito utiliza reagentes baratos e pode ser executado em quatro etapas. As etapas de oxidação e de tratamento ácido não afetam a cadeia lateral espirocetálica presente na diosgenina (16).

 

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Acknowledgments

We are indebted to CONACyT, Mexico, for financial support via grant 35235-E and the scholarships granted to S.X.M and O.V.B. We also want to acknowledge Professor Benjamín Ruiz for laboratory facilities at the Facultad de Química of UNAM.

 

References

1. Hill, R. A.; Makin, H. L. J.; Kirk, D. N.; Murphy, G. M., eds.; Dictionary of Steroids, Chapman and Hall: London, 1991.         [ Links ]

2. Adam, G.; Marquardt, V.; Phytochemistry 1986, 25, 1787.         [ Links ]

3. Jizba, J.; Herout, V.; Collect. Czech. Chem. Commun. 1967, 32, 2867.         [ Links ]

4. Takeda, K.; Shimaoka, A.; Iwasaki, M.; Minato, H.; Chem. Pharm. Bull. 1965, 13, 691.         [ Links ]

5. Behr, D.; Berg, J. E.; Karlsson, B.; Leander, K.; Pilotti, A. M.; Wiehager, A. C.; Acta Chem. Scand. (B) 1975, 29, 401.         [ Links ]

6. Nakahatov, I.; Nabiev, A.; Shakirov, R.; Yusonov, S.; Khim. Prir. Soedin 1983, 6, 747. (CA 100: 188749)        [ Links ]

7. Nakahatov, I.; Nabiev, A.; Shakirov, R.; Khim. Prir. Soedin. 1981, 4, 616. (CA 96: 65672x)        [ Links ]

8. Okanishi, T.; Akahor, A.; Yasuda, F.; Chem. Pharm. Bull. 1965, 13, 545;         [ Links ] Iglesias-Arteaga, M. A.; Perez Gil R.; Perez Martinez C. S.; Coll Manchado, F.; J. Chem. Soc., Perkin Trans. 1 2001, 261.         [ Links ]

9. Henbest, H. B.; Wrigley, T. I.; J. Chem. Soc. 1957, 4765;         [ Links ] Ramírez, J. A.; Gros, E. G.; Galagovsky, L. R.; Tetrahedron 2000, 56, 6171.         [ Links ]

10. Syamala, M. S.; Das, J.; Baskaran, S.; Chandrasekaran, S.; J. Org. Chem. 1992, 57, 1928;         [ Links ] Parish, E. J.; Li, H.; Li, S.; Synth. Commun. 1995, 25, 927;         [ Links ] Hanson, J. R.; Hitchock, P. B.; Liman, M. D.; Nagaratnam, S.; Manickavasagar, R.; J. Chem. Res. (S) 1995, 220;         [ Links ] Parish, E. J.; Li, S.; J. Chem. Res. (S) 1996, 288;         [ Links ] Parish, E. J.; Li, S.; J. Org. Chem. 1996, 61, 5665;         [ Links ] Salvador, J. A. R.; Sáe Melo, M. L.; Campos Neves, A. S.; Tetrahedron Lett. 1996, 37, 687;         [ Links ] Salvador, J. A. R.; Hanson, J. R.; J. Chem. Res. (S) 2002, 576.         [ Links ] The authors became aware that, after submission of the present paper, a different and convenient method for β-epoxidation of Δ⁵-steroids using Co(II) salts and molecular oxygen had been published: Silvestre, S. M.; Salvador, J. A. R.; Clark, J. H.; J. Mol. Catal. A: Chemical 2004, 219, 143.         [ Links ]

11. Chakravorty, P. N.; Levin, R.; J. Am. Chem. Soc. 1942, 64, 2317.         [ Links ]

12. James, D. R.; Shoope. C. W.; J. Chem. Soc. 1954, 4224.         [ Links ]

13. Heilbron, I. M.; Jones, E. H. R.; Spring, F. S.; J. Chem. Soc. 1937, 801.         [ Links ]

14. Fonken, G. J.; Miles, H. M.; J. Org. Chem. 1963, 28, 2432.         [ Links ]

15. Dodson, R. G.; Riegel, B.; J. Org. Chem. 1948, 13, 424.         [ Links ]

16. Bowers, A.; Denot, E.; Cuéllar Ibáñez, L.; Cabezas, M. E.; Ringold, H. J.; J. Org. Chem. 1962, 27, 1862.         [ Links ]

17. Elks, J. In Rodd's Chemistry of Carbon Compounds; Coffey, S., ed., Elsevier Publ. Co.: Amsterdam, 1971, ch. 18.         [ Links ]