5 research outputs found
An Easy And Efficient Method To Produce γ-amino Alcohols By Reduction Of β-enamino Ketones
Reduction of β-enamino ketones 2 with NaBH4 in glacial acetic acid gave γ-amino alcohols 1 in 70% to 98% yield with diastereomeric excesses, preferentially the syn product, from 44% to 90%. The stereochemistry of these compounds was confirmed by analysis of their tetrahydro-1,3-oxazine derivatives 3.156971975Gevorgyan, G.A., Agababian, G., (1984) Russ. Chem. Rev., 53, p. 581Jäger, V., Buß, V., (1980) Liebigs Ann. Chem., p. 101Wang, Y.F., Izawa, T., Kobayashi, S., Ohno, M., (1982) J. Am. Chem. Soc., 104, p. 6465Heitsch, H., König, W.A., Decker, H., Bormann, C., Fiedler, H.P., Zähner, H., (1989) J. Antibiotics, 42, p. 711Wovkulich, P.M., Uskokovic, M.R., (1981) J. Am. Chem. Soc., 103, p. 3956Jäger, V., Schwab, W., Bub, V., (1981) Angew. Chem. Int. Ed. Engl., 20, p. 601White, D.W., Gibbs, D.E., Verkade, J.G., (1979) J. Am. Chem. Soc., 101, p. 1937Liguori, A., Romeo, G., Sindona, G., Ucella, N., (1988) Chem. Ber., 121, p. 105Bongini, A., Cardillo, G., Orena, M., Porzi, G., Sandri, S., (1988) Chem. Lett., p. 87Arisa, J., Font, J., Ortuño, R.M., (1990) Tetrahedron, 46, p. 1931Narasaka, K., Ukaji, Y., Yamazaki, S., (1986) Bull. Chem. Soc. Jpn., 59, p. 525Maroni, P., Gazaux, L., Tisnes, P., Zambeti, M., (1980) Bull. Soc. Chim. Fr. P II, p. 179Matsumura, Y., Fujiwara, J., Maruoka, K., Yamamoto, H., (1983) J. Am. Chem. Soc., 105, p. 6312Bartoli, G., Cimarelli, C., Palmieri, G., (1994) J. Chem. Soc., Perkin Trans. 1, p. 537Bartoli, G., Cupone, G., Dalpozzo, R., De Nino, A., Maiuolo, L., Procopio, A., Tagarelli, A., (2002) Tetrahedron Lett., 43, p. 7441Greenhill, J.V., (1977) Chem. Soc. Rev., 6, p. 277Schuda, P.F., Ebner, C.B., Morgan, T.M., (1986) Tetrahedron Lett., 27, p. 2567Barluenga, J., Aguilar, E., Fustero, S., Olano, B., Viado, A.L., (1992) J. Org. Chem., 57, p. 1219Katritzky, A., Harris, P.A., (1990) Tetrahedron, 46, p. 987Pilli, R.A., Russowsky, D., Dias, L.C., (1990) J. Chem. Soc., Perkin Trans. 1, p. 1213Tramontini, M., (1982) Synthesis, p. 605Gribble, G.W., Nutaitis, C.F., (1985) Org. Prep. Proc. Int., 17, p. 317Gribble, G.W., (1998) Chem. Soc. Rev., 27, p. 395Harris, M.I.N.C., (1993) PhD. Thesis, , Universidade Estadual de Campinas, BrazilBraga, A.C.H., Harris, M.I.N.C., CA, 128, p. 243740. , Br PI 9.502.467-0, 1995noteBarluenga, J., Olano, B., Fustero, S., (1985) J. Org. Chem., 50, p. 405
Studies On The Reduction Of β-enamino Ketones
Reduction of β-enamino ketones 1 with NaBH(OAc)3 in glacial acetic acid gave β-amino ketones 3 in 65% to 67% yield. These data and others observed in the reduction of β-enamino ketones 1 to preferentially syn γ-amino alcohols 2 with NaBH4/HOAc suggest that in this last reaction we have firstly the reduction of the β-enamino ketones 1 to produce the β-amino ketones 3, and then this compound is reduced to the γ-amino alcohols 2. We can say from this results that the diastereosselectivity of the reduction of β-enamino ketones 1 to mainly syn γ-amino álcohols 2, can be analysed as a competition between a chair-like transition state and a boat-like transition state, obtained from the β-amino ketones 3. © 2006 Sociedade Brasileira de Química.17714401442Harris, M.I.N.C., Braga, A.C.H., (2004) J. Braz. Chem. Soc., 15, p. 971Harris, M.I.N.C., (1993), Ph.D. Thesis, Universidade Estadual de Campinas, BrazilBraga, A. C. H.Harris, M. I. N. C.Br PI 9.502.467-0, 1995. (CA 128:243740)Gribble, G.W., Nutaitis, C.F., (1985) Org. Prep. Proced. Int., 17, p. 317Gribble, G.W., (1998) Chem. Soc. Rev., 27, p. 395For a better understanding of this reactivity, theoretical studies are in progressnoteMarchini, P., Liso, G., Reho, A., (1975) J. Org. Chem., 40, p. 3453Evans, D.A., Chapman, K.T., Carreira, E.M., (1988) J. Am. Chem. Soc., 110, p. 3560Palmieri, G., Cimarelli, C., (2006) Arkivoc, p. 10
Development of mesalazine pellets coated with methacrylic-derived polymer
Mesalazine (5-ASA) is the standard drug for the treatment of inflammatory bowel disease (IBD) due to its local effect on intestinal and colonic mucosa. The effective and safe treatment of this disease requires more efficient delivery of the active substance to its site of action. The focus of this study was the use of multiparticulate systems, a modified release form in which the drug is divided into several functional subunits of release in the form of granules or pellets. When these forms are administered, they are rapidly disintegrated, distributing their content throughout the gastrointestinal tract. The aim of this study was to develop and evaluate a multiparticulate system consisting of pellets coated with polymer for pH-dependent release, derived from methacrylic acid and incorporated into the tablet dosage form of mesalazine as a model drug. The extrusion-spheronisation technique was used, resulting in smooth and spherical pellets with uniform size distribution, which were coated in fluidized bed using Opadry® Enteric 94K28327 containing Eudragit® S100 as the agent regulating drug release. The dissolution profile of coated pellets showed good control of drug release from the polymer at the two levels of coating evaluated (8% and 10%), but only the 10% coated pellets were statistically similar to Asalit® 400 mg.<br>A mesalazina (5-ASA) tem se apresentado como fármaco padrão para o tratamento da doença inflamatória intestinal (DII) devido ao seu efeito local na mucosa intestinal e colônica. A terapia efetiva e segura desta doença requer a chegada da substância ativa ao seu local de ação com maior eficiência. Nessa busca, tem se destacado o uso de Sistemas Multiparticulados, forma farmacêutica de liberação modificada, em que o fármaco está dividido em várias subunidades funcionais de liberação, sob a forma de grânulos ou péletes, que quando administrados, são rapidamente desintegrados distribuindo seu conteúdo por todo trato gastrintestinal. Este trabalho teve como objetivo desenvolver e avaliar péletes revestidos com polímero de liberação pH-dependente, derivado do ácido metacrílico, tendo como fármaco modelo a mesalazina. A técnica de extrusão-esferonização foi utilizada obtendo-se péletes lisos e esféricos com distribuição granulométrica uniforme, que foram revestidos em leito fluidizado utilizando Opadry® Enteric 94K28327 contendo Eudragit® S100 como agente regulador da liberação do fármaco. O perfil de dissolução dos péletes revestidos demonstrou bom controle na liberação do fármaco por parte do polímero nos dois níveis de revestimento avaliados (8 e 10%), porém, apenas os péletes revestidos a 10% demonstraram semelhança estatística com o medicamento de referência Asalit® 400 mg