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Journal of the Mexican Chemical Society
versión impresa ISSN 1870-249X
J. Mex. Chem. Soc vol.53 no.3 Ciudad de México jul./sep. 2009
Article
Photochemical Rearrangement of a 6Azasteroid Oxaziridine to a Novel 17βCarbomethoxyAhomoBseco6aza3, 5androstanedione
Stephen Frye*
Department of Medicinal Chemistry, Glaxo Inc. Research Institute, Five Moore Drive, Research Triangle Park, North Carolina.
Received June 23, 2009
Accepted August 31, 2009
* Current contact information:
UNC Eshelman School of Pharmacy,
Division of Medicinal Chemistry and the Center for Integrative Chemical Biology and Drug Discovery,
120 Mason Farm Road,
Campus Box 7363,
University of North Carolina,
Chapel Hill, NC 275997363;
email: svfrye@email.unc.edu;
phone: 919 843 5486.
Abstract
4 and 6azasteroids have been shown to be potent inhibitors of human 5α,reductase and certain azasteroids have shown significant clinical benefit in the treatment of androgenrelated disorders. In an effort to expand the diversity of steroidal heterocycles synthetically accessible for structureactivity relationship exploration, a novel reaction sequence was applied to the preparation of the 6azasteroid framework. To this end, photolysis of the oxaziridine derived from 17βcarbomethoxy3βtriisopropylsilyloxy6azaandrost5ene (1) yielded a novel 7, 5steroidal ring system that was evaluated for inhibition of human type 1 and 2 5αreductase.
Key words: Azasteroids, 5αreductase, steroidal heterocycles, photochemistry, synthesis, oxaziridine.
Resumen
Los 4 y 6azaesteroides mostraron ser potentes inhibidores de la 5α,reductasa humana, y otros azaesteroides fueron eficientes en el tratamiento clínico de desórdenes relacionados a los andrógenos. En un esfuerzo para ampliar la diversidad de heterociclos esteroidales que se obtengan sintéticamente, con el fin de explorar sus relaciones de estructuraactividad, se empleó una novedosa secuencia de reacciones para la preparación de 6azaesteroides. De esta forma, la fotólisis de la oxaziridina derivada del 17βcarbometoxi3βtriisopropilsililoxi6azaandrost5eno (1) proporcionó un nuevo sistema esteroidal de anillos fusionados de 5 y 7 miembros, el cual se evaluó en la inhibición de la 5αreductasa humana de tipos 1 y 2.
Palabras clave: Azaesteroides; 5αreductasa; heterociclos esteroidales; fotoquímica,; síntesis; oxaziridina.
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Acknowledgments
This paper is dedicated to the memory of Professor Ernest Eliel a gentleman and scholar who gave so much to chemistry and the world.
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