SciELO - Scientific Electronic Library Online

 
vol.46 número1STUDIES ON CHILEAN LICHENS XXXI: ADDITIONS TO THE CHEMISTRY OF PSEUDOCYPHELLARIA2,3-FUNCTIONALLY DIALKYL-1,4-BENZOHYDROQUINONE DIACETATE DERIVATIVES FROM CLEAVAGE OF EPOXIDES índice de autoresíndice de assuntospesquisa de artigos
Home Pagelista alfabética de periódicos  

Serviços Personalizados

Journal

Artigo

Indicadores

Links relacionados

Compartilhar


Boletín de la Sociedad Chilena de Química

versão impressa ISSN 0366-1644

Bol. Soc. Chil. Quím. v.46 n.1 Concepción mar. 2001

http://dx.doi.org/10.4067/S0366-16442001000100006 

CHEMICAL-MICROBIOLOGICAL SYNTHESIS
OF PROGESTERONE

L. VASQUEZ*, J. ALARCON**, H. ZUNZA***, J. BECERRA* AND M. SILVA*

(*)Lab. Química de Productos Naturales, U. de Concepción, Concepción, Chile
(**)Dpto. Ciencias Básicas, Fac. de Ciencias, U. del Bio Bio, Chillán, Chile.
(***)Dpto. Química Orgánica, Fac. Ciencias Química, U. de Concepción, Concepción, Chile.
(Received: January 20, 2000 - Accepted: September 28, 2000)

ABSTRACT

Progesterone 3 was obtained by oxidation of 20(S)-hydroxymethylpregn-4-en-3-one 1, with pyridinium chlorochromate. The precursor was obtained by selective microbial degradation of b-sitosterol.

KEYWORDS: Mycobacterium fortuitum, steroids, microbial transformation, oxidation.

RESUMEN

Progesterona 3 fue obtenida por oxidación de 20(S)-hidroximetilpregn-4-en-3-ona 1 con clorocromato de piridinio. El precursor se obtuvo mediante una degradación selectiva de b-sitosterol.

PALABRAS CLAVES: Mycobacterium fortuitum, esteroides, biotransformación, oxidación.

This paper deals with the production of progesterone starting from b-sitosterol by a biotransformation process, followed by oxidation of 20-hydroxymethylpregn-4-en-3-one with pyridinium chlorochromate (PCC) , a reaction which has not been previously reported.

Microbial degradation of b-sitosterol by a Mycobacterium fortuitum mutant produces androst-4-ene-3,17-dione and androst-1,4-diene-3,17-dione . However, when an inhibitory agent is used it is possible to effect the selective microbial degradation of the 17-alkyl side chain1,7. Furthermore, when 1-propanol (2.0 % v/v) was used as inhibitor in a typical aerobic fermentation, 20-hydroxymethylpregn-4-en-3-one 1 was obtained* .(fig.1).


A solution of the 20-hydroxymethylpregn-4-en-3-one 1 ( 0.2 g) in dry dichloromethane (50 ml) was rapidly added to a suspension of pyridinium chlorochromate (0.065 g) in dry dichloromethane with stirring. The reaction9 mixture was stirred at room temperature during 15 minutes. Then, ether was added and the mixture was filtered through a small amount of silica gel8. The solvent was dried and evaporated to give 20-formylpregn-4-en-3-one 2 as a white solid (93% yield).

However, when the reaction was carried out in the presence of a small amount of water (drops) it yielded a mixture of compounds 2, 3 and 4 (fig.2). These results suggest the formation of chromic acid by a reaction between water and the pyridinium chlorochromate. In a first step the chromic acid presumably oxidizes the aldehyde to the corresponding carboxylic acid 4. Probably the progesterone is formed as a consequence of oxidative decarboxylation of 4. A similar process has been described in the presence of other ions like Co(III), Ag(II), Mn(III) and Ce(IV)9. Presently, our group is studying this reaction in detail in order to increase the progesterone yield.

The effect of the temperature and the reaction time were studied and the results are shown in table 1.

The compounds were separated and purified by column chromatography eluting with EtOAc: petrol. The structures were established by their physical and spectral data and comparison with data already described in the literature.


ACKNOWLEDGEMENT

We acknowledge the financial support given by Dirección de Investigación U. de Concepción; DIPRODE-U. del Bío Bío; Escuela de Graduados de la U. de Concepción; FONDEF D96-1111.We are grateful to Dr. Joel Alderete and Miss Silvia Fernandez for the NMR measurements.

Data taken the Master of Science Thesis of L. Vásquez

REFERENCES

1. J. Gregory Reid and Th. Debiak-Krook (1990) Tetrahedron Lett. 31, 3669-3672.         [ Links ]

2. N.V. Kovganko and Zh. N. Kashkan (1994) Chemistry of Natural Compounds 30(5),533-546.        [ Links ]

3. N. Applezweig "Steroid Drugs" McGraw-Hill, New York, 1962, pp.41-46.        [ Links ]

4. L.F.Fieser and M. Fieser "Steroids" Reinhold, N.Y., 1959, chapter 19.        [ Links ]

5. M.G. Wovcha, F.J. Antosz, J.C. Knight, L.A. Kominek and T.R. Pyke (1978) Biochim. Biophys. Acta 531, 308-321.        [ Links ]

6. G. Mix. K.G. Buki, E. Tomorkeny and G. Ambous (1968) Steroids 11, 401-413.        [ Links ]

7. M. Nagasawa, M. Bae, G. Tamura and K. Arima (1969) Agr. Biol. Chem. 33, 1644-1650.        [ Links ]

8. G. Piancatelli, A. Scettri and M. D’Auria (1982) Synthesis, 245-258.        [ Links ]

9. J. March "Advanced Organic Chemistry" John Wiley &Sons. New York, 1992, chapter 19.        [ Links ]

Creative Commons License Todo o conteúdo deste periódico, exceto onde está identificado, está licenciado sob uma Licença Creative Commons