User:Muchowski/sandbox

Joseph Muchowski (born January 30, 1937) is an organic chemist specializing in heterocyclic chemistry. Muchowski is best known for leading the research group at Syntex Corp. (now Roche Bioscience, which is a wholly owned subsidiary of Roche holding Ltd., the parent company of Roche) who discovered Ketorolac or ketorolac tromethamine, a non-steroidal anti-inflammatory drug (NSAID) in the family of heterocyclic acetic acid derivatives, used as an analgesic. He holds 60 U. S. patents and has authored over 150 papers. His current research interests are in the areas of reaction mechanisms, synthetic methodology development with a strong heterocyclic flavor, hydrogen bonding, hindered bases, total synthesis of natural products, and compounds of medicinal importance.

Education
Muchowski was born in Odessa, Canada, the grandson of Polish immigrants and farmers. In 1940 the family moved to a new farm in the even smaller nearby hamlet of Candiac. There he received his education in grades 1-8 in a one-room schoolhouse, and then grades 9-11 in a slightly larger two-room school. For his final year of secondary education he attended Regina College in Regina, Saskatchewan, and stayed there for his first year of University studies. His favorite subject was history, and he had dreams of being a pilot, but his parents urged him to do something more practical, and so he chose chemistry. He attended the University of Saskatchewan in Saskatoon, where he was introduced to organic chemistry by a young visiting professor (Alan Vanterpool) and was hooked on this area. Joe received his B. A. degree with honours in Chemistry, and the M. A. in Organic Chemistry in 1959, with a thesis "Studies in Indole Chemistry" under the supervision of Professor R. A. Abramovitch. This began Joe's life-long passion for heterocyclic chemistry. He received a Ph.D. in 1962 from the University of Ottawa under the tutelage of Professor Frank A. L. Anet with a thesis "Heterocyclic Nitrogen Compounds", and spent a postdoctoral stint at the Eidgenosciche Technische Hochschule ETH in Zurich in the group of Professor Albert Eschenmoser, where he engaged in studies related to the total synthesis of Vitamin B12.

Research and career
In 1963 Muchowski returned to Canada at Bristol Laboratories in Candiac, Quebec, where he carried out medicinal chemistry research, and then in 1971 moved to Syntex, S. A., in Mexico City. There he became Director of Chemical Research in 1974, and in 1975 he was also named Assistant Director of the Institute of Organic Chemistry of Syntex Corp. in Palo Alto, California. During 1974-1976 he was also Adjunct Professor at the Universidad Iberoamericana in Mexico City, where he lectured in heterocyclic and mechanistic organic chemistry to undergraduate and postgraduate students. In 1977 he moved to the Institute of Organic Chemistry of Syntex Corp. in Palo Alto while maintaining his responsibilities with Syntex in Mexico. In 1995 when Syntex became part of Roche of Switzerland he took early retirement. However true to his nature, he has continued at Roche as a consultant, and also became Visiting Professor at the Universidad Nacional Autónoma de México in Mexico City, where he continues to teach regularly.

During his tenure as the Director of Chemical Research of Syntex Corp., Muchowski's research group played a fundamental role in the development of Fenprostalene (feed lot abortificient in cattle) and Ketorolac (non-narcotic analgesic equipotent with morphine), both of which reached the marketplace. Ketorolac (Toradol) is used worldwide for the relief of moderate to severe pain in post operative situations and in trauma clinics. In 1985 he received the Syntex Science Award and President's Medal in recognition for these significant and innovative contributions. Muchowski is a member of the American Chemical Society and the Chemical Institute of Canada. In 1977 Joe was elected to the Mexican Academy of Scientific Research, and in 2002 he became a Fellow of the Chemical Institute of Canada. He was the Mexican Chairman and organizer of the organic chemistry section of the First Chemical Congress of the North American Continent, which was held in Mexico City in 1975, and was a member of the Advisory board of the Journal of Organic Chemistry (1985-1990). He has directed the thesis studies of more than 20 students at the B. Sc., M. Sc. and Ph. D. levels, and has had 22 post doctorate fellows and 3 visiting professors as research collaborators. Muchowski holds 60 U. S. patents and has authored over 150 papers. His current research interests are in the areas of reaction mechanisms, synthetic methodology development with a strong heterocyclic flavor, hydrogen bonding, hindered bases, total synthesis of natural products, and compounds of medicinal importance.

Significant publications
Synthesis of 11-Hydroxymethylprostaglandins. A. Guzmán and J.M. Muchowski. Tetrahedron Letters. 2053 (1975).

The Reaction of Di and Trialkylchloroiminium Chlorides with Azide Ion. A New “Curtius Type” Rearrangement.R. Imhof, D.W. Ladner and J.M. Muchowski. J. Org. Chem. 42, 3709 (1977).

One Step Synthesis of 3,8-Methanoaza[10]Annulene Derivatives. M. Maddox, J. Martin, and J.M. Muchowski. Tetrahedron Letters. 21,7 (1980).

New Heterocyclic Systems. Benzo[4,5]cycloheptal[1,2-b]- pyrrole and Benzo[5,6]cyclohepta[1,2-f] pyrrolizidine Derivatives. J. Ackrell, F. Franco, R. Greenhouse, A. Guzmán, and J.M. Muchowski. J. Heterocyclic Chem. 17, 1081 (1980).

Synthesis and Rearrangement of 2-Aryl- and 2-Alkylsulfinylpyrroles. O. Carmona, R. Greenhouse and J.M. Muchowski. J. Org. Chem. 45, 5336 (1980).

Novel Syntheses of 5-Aroyl-1,2-dihydro-3H-pyrrolo[1,2-a]- pyrrole-1-carboxylic Acids. F. Franco, R. Greenhouse and J.M. Muchowski. J. Org. Chem. 47, 1682 (1982).

One Step Synthesis of 3,8-Methano-1-aza[10]annulene Derivatives via Diels-Alder Reaction of Benzocyclopropene with 1,2,4-Triazines. J.C. Martin and J.M. Muchowski. J. Org. Chem. 49, 1040 (1984).

Catalytic Hydrogenation of Pyrroles at Atmospheric Pressure. H-P. Kaiser and J.M. Muchowski. J. Org. Chem. 49, 4203 (1984).

Synthesis, Antiinflammatory and Analgesic Activity of 5-Aroyl-,2-dihydro-3H- pyrrolo[1,2-a]pyrrole- 1-carboxylic Acids and Related Compounds.J.M. Muchowski, S.H.      Unger, J. Ackrell, P. Cheung, J. Cook, G.F. Cooper, P. Gallegra, O. Halpern, R. Koehler, A.F. Kluge, A.R. Van Horn, Y. Antonio, H.Carpio, F. Franco, E. Galeazzi, I. Garcia, R.     Greenhouse, A. Guzmán, J. Iriarte, A. Leon, A. Pena, V. Peréz, D. Valdez, N. Ackerman, S.A. Ballaron, D.V. Krishna Murthy, J.R. Rovito, A.J. Tomolonis, J.M. Young and W.H.     Rooks. J. Med. Chem. 28, 1037 (1985).

Absolute Configuration of (-)-5-Benzoyl-1,2- dihydro-3H-pyrrolo[1,2-a]pyrrole-1- carboxylic Acid, the Active Enantiomer of Ketorolac. A. Guzmán, F. Yuste, R.A. Toscano, J.M. Young, A.R. Van Horn, J.M. Muchowski. J.Med. Chem. 25,589 (1986).

Synthesis and Antinflammatory and Analgesic Activity of 5-Aroyl-l,2-dihydro-3H- pyrrolo[1,2-a]pyrrole-1- carboxylic Acids. The 6-Substituted Compounds. J.M. Muchowski, G. F. Cooper, O. Halpern, R. Koehler, A. F. Kluge, R. C. Simon, S. H. Unger, A. R. Van Horn, D. L. Wren, J. Ackrell, Y. Antonio, F. Franco, R. Greenhouse, A. Guzman, A. Leon, N. Ackerman, S. A. Ballaron, D. V. Krishna Murthy, J. R. Rovito, A. J. Tomolonis, J. M. Young, W. H. Rooks, J.Med. Chem. 30, 820 (1987).

Synthesis and Antiinflammatory and Analgesic Activity of 5-Aroyl-6-methylthio-1,2- dihydro-3H-pyrrolo-[1,2-a]pyrrole-1-carboxylic Acids and 1-Methyl-4- methylthio-5- aroylpyrrole-2-acetic Acids. J.M. Muchowski, E. Galeazzi, R. Greenhouse, A. Guzman, V. Perez, N. Ackerman, S.A. Ballaron, J.R. Rovito, A.J. Tomolonis, J.M. Young and W. H. Rooks. J. Med. Chem. 32, 1202 (1989).