Stereoselective Crystallization as a Key Step for the Synthesis of New Epimers of Captopril Derivatives
Aurelio Ortiz,1* Omar Arellano,1 Estibaliz Sansinenea2 and Sylvain Bernès3
1 Facultad de Ciencias Químicas de la Benemérita Universidad Autónoma de Puebla.
2 Instituto de Ciencias de la Benemérita Universidad Autónoma de Puebla, 72570, Puebla, Puebla, México.
3 Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Monterrey, N. L. 64570, México.
]]>Recibido el 30 de agosto de 2007
Aceptado el 17 de diciembre de 2007
Abstract
The present work describes the synthesis of two new diastereomers of captopril derivatives. These epimers were achieved by conjugate addition of thioacetic acid and α-toluenethiol to a α,β-unsaturated system. The diastereomeric ratios obtained from this reaction were low at 0 oC and moderate at -50 oC. The importance of this synthesis, however, is that in one case, both epimers can be isolated in good yields. Their isolation was possible because of the high crystallinity showed by one epimer compared to the other one. The absolute configuration of the solid compound was established by X-ray analysis.
Key words: Captopril, ACE inhibitor, antihypertensive, conjugate addition of thiols.
Resumen
El presente trabajo describe la síntesis de dos nuevos diastereómeros derivados del captopril. Estos epímeros fueron obtenidos a través de la adición conjugada del ácido tioacético y α-toluenotiol a un sistema α, β-insaturado. Las relaciones diastereoméricas para esta reacción fueron bajas a 0 oC y moderadas a -50 oC. Sin embargo, la importancia de esta síntesis radica en que, en un caso, ambos epímeros pueden ser separados en rendimientos químicos aceptables. La separación de los epímeros fue posible debido a la alta cristalinidad que presentó un epímero en comparación del otro. La configuración absoluta del epímero cristalino fue establecida por difracción de Rayos-X.
]]> Palabras clave: Captopril, Inhibidor ACE, antihipertensivo, adición conjugada de tioles.
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Acknowledgments
We thank CONACyT (project 53533). We wish to thank Prof. Herbert Hòpfl (from Morelos State University, UAEM) for critical reading of the manuscript.
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