Metal Carbene N-h Insertion Of Chiral α, α′-dialkyl α-diazoketones. A Novel And Concise Method For The Stereocontrolled Synthesis Of Fully Substituted Azetidines

The syntheses of all cis substituted azetidines were accomplished in few steps from L-serine in modest to high yields. The key step was based on a rhodium or copper carbenoid N-H insertion of α,α′- dialkyl-α-diazoketones to furnish cis-2,4-dialkyl-azetidin-3-ones as the only observable diastereoisomers. © 2004 Elsevier Ltd. All rights reserved.451733553358Kobayashi, J., Ishibashi, M., Walchli, M.R., Yamamura, S., Ohizumi, Y., (1996) J. Chem. Soc. Heterocycles, 42, p. 943Kobayashi, J., Cheng, J., Ishibashi, M., Walchli, M.R., Yamamura, S., Ohizumi, Y., (1991) J. Chem. Soc., Perkin Trans. 1, p. 1135Alvi, K.A., Jaspars, M., Crews, P., (1994) Bioorg. Biomed. Chem. Lett., 4, p. 2447Hiraki, T., Yamagiwa, Y., Kamikawa, T., (1995) Tetrahedron Lett., 36, p. 4841. , For previous synthesis of azetidine alkaloids and analogues, see:Takikawa, H., Maeda, T., Mori, K., (1995) Tetrahedron Lett., 36, p. 7689Yoda, H., Oguchi, T., Takabe, K., (1996) Tetrahedron: Asymmetry, 7, p. 2113Yashima, A., Takikawa, H., Mori, K., (1996) Liebigs Ann., 7, p. 1083Mori, K., (1996) J. Heterocyclic Chem., 33, p. 1497Yoda, H., Oguchi, T., Takabe, K., (1997) Tetrahedron Lett., 38, p. 3283Knapp, S., Dong, Y., (1997) Tetrahedron Lett., 38, p. 3813Takikawa, H., Maeda, T., Seki, M., (1997) J. Chem. Soc., Perkin Trans. 1, 2, p. 97Lin, G.Q., Liu, D.G., (1998) Heterocycles, 47, p. 337Lin, G.Q., Liu, D.G., (1999) Tetrahedron Lett., 40, p. 337Reference 2j cited in [3l]Salgado, A., Boeykens, M., Gauthier, C., Declercq, J., De Kimpe, N., (2002) Tetrahedron, 58, p. 2763Yoda, H., Uemura, T., Takabe, K., (2003) Tetrahedron Lett., 44, p. 977Salgado, A., Boeykens, M., Gauthier, C., Dejaegher, Y., Verniest, G., Lopin, C., Tehrani, K.A., De Kimpe, N., (2003) Tetrahedron, 59, p. 2231Dejaegher, Y., Kuz'Nenok, N.M., Zvonok, A.M., De Kimpe, N., (2002) Chem. Rev., 102, p. 29Doyle, M.P., McKervey, M.A., Ye, T., (1998) Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides, , New York: John Wiley and SonsMoyer, M.P., Feldman, P.L., Rapoport, H., (1985) J. Org. Chem., 50, p. 5223Emmer, G., (1992) Tetrahedron, 48, p. 7165Hanessian, S., Fu, J., Chiara, J.L., Di Fabio, R., (1993) Tetrahedron Lett., 34, p. 4157Podlech, J., Seebach, D., (1995) Helv. Chim. Acta, 78, p. 1238Sengupta, S., Das, D., (1998) Synth. Commun., 28, p. 403Desai, P., Aubé, J., (2000) Org. Lett., 2, p. 1657Pusino, A., Saba, A., Desole, G., (1985) Gazzeta Chim. Italiana, 115, p. 33Wang, J., Hou, Y., Wu, P., (1999) J. Chem. Soc., Perkin Trans. 1, p. 2277Garner, P., Park, J.M., (1987) J. Org. Chem., 52, p. 2361notenoteCraig, D., Berry, M.B., (1992) Synlett, p. 41Taber, D.F., You, K.K., Rheigold, A.L., (1996) J. Am. Chem. Soc., 118, p. 547Doyle, M.P., Westrum, L.J., Wolthuis, W.N.E., See, M.M., Boone, W.P., Bagheri, V., Pearson, M.M., (1993) J. Am. Chem. Soc., 115, p. 958See reference 9 cited in reference 12 belowNakamura, E., Yoshikai, N., Yamanaka, M., (2002) J. Am. Chem. Soc., 124, p. 7181Davis, F.A., Yang, B., Deng, J., (2003) J. Org. Chem., 68, p. 5147not

Synthesis Of Aryl Pyrrolizidines From Endocyclic Enecarbamates. Novelapplications Of The Heck Arylation Of 3-pyrrolines Using Diazonium Salts

The novel aryl platynecines 3a/3b were synthesized from endocyclic 4-aryl enecarbamates 8a/8b by a concise and practical route. The synthesis was based on an efficient preparation of 4-aryl enecarbamates 8a/8b from 3-pyrrolines by means of a Heck arylation using aryldiazonium tetrafluoroborates, followed by a highly stereoselective cycloaddition of the 4-aryl enecarbamates 8a/8b to 2-chloroethyl ketene to afford exclusively the 7-endo-(2-chloroethyl) cyclobutanones 12a/12b in good yields (67% and 65%). Baeyer-Villiger oxidation of the cyclobutanones 12a/12b occurred with high regioselectivity to furnish the aza-lactones 13a/13b in 96% and 90% yields. Reduction of lactones 13a and 13b with LiAlH4 gave the desired aryl platynecines 3a/3b. The total synthetic sequence involved 6 steps and provided the aryl platynecines 3a/3b in an overall yield of 41% and 38%, respectively. These compounds are the first examples of necine bases bearing an aromatic substituent on the azabicyclo[3.3.0]octane framework and incorporate some of the key structural element of the pharmacologically active 1,3,4-trisubstituted pyrrolines which act as antagonists of the chemokine receptor CC5.200310390403Liddel, J.R., (2000) Nat. Prod. Rep., 17, p. 455Robins, D., (1989) Chem. Soc. Rev., 18, p. 375Mattoc, A.R., (1986) Chemistry and Toxicology of Pyrrolizidine Alkaloids, , Academic Press: LondonCooper, R.A., Huxtable, R., (1996) Toxicon, 34, p. 604Couet, C.E., Hopley, J., Hanley, A.B., (1996) Toxicon, 34, p. 1058Ober, D., Hartmann, T., (1999) J. Bio. Chem., 274, p. 32040Gordon, G.J., Coleman, W.B., Grisham, J.W., (2000) Experimental and Molecular Pathology, 69, p. 17Hanselmann, R., Benn, M., (1993) Tetrahedron Lett., 34, p. 3511Faria, A.R., Salvador, E.L., Correia, C.R.D., (2002) J. Org. Chem., 67, p. 3651Faria, A.R., Matos, C.R., Correia, C.R.D., (1993) Tetrahedron Lett., 34, p. 27Faria, A.R., Carvalho, E.S., Correia, C.R.D., (1995) Tetrahedron Lett., 36, p. 5109Willoughby, C.A., Rosauer, K.G., Hale, J.J., Budhu, R.J., Mills, S.G., Chapman, K.T., MacCoss, M., Emini, E.A., (2003) Bioorg. Med. Chem. Lett., 13, p. 427Lynch, C.L., Hale, J.J., Budhu, R.J., Gentry, A.L., Mills, S.G., Chapman, K.T., MacCoss, M., Emini, E.A., (2002) Bioorg. Med. Chem. Lett., 12, p. 3001Hale, J.J., Budhu, R.J., Mills, S.G., MacCoss, M., Gould, S.L., DeMartino, J.A., Springer, M.S., Emini, E.A., (2002) Bioorg. Med. Chem. Lett., 12, p. 2997Lynch, C.L., Hale, J.J., Budhu, R.J., Gentry, A.L., Finke, P.E., Caldwell, C.G., Mills, S.G., Emini, E., (2003) Org. Lett., 5, p. 2473Garcia, A.L.L., Correia, C.R.D., (2003) Tetrahedron Lett., 44, p. 1553Carpes, M.J.S., Correia, C.R.D., (2000) Synlett, 7, p. 1037Oliveira, D.F., Miranda, P.C.M.L., Correia, C.R.D., (1999) J. Org. Chem., 64, p. 6646Roe, A., (1949) Org. React., 5, p. 193Cabri, W., Candiani, I., (1995) Acc. Chem. Res., 28, p. 2Hallberg, A., Clas, S., Larbed, M., Nyqvist, C., (1996) J. Org. Chem., 61, p. 4756Krow, G.R., (1991) Comprehensive Organic Synthesis, 7, p. 671. , Ley, S. V. Ed.Pergamom Press: Oxfor

Controle de larvas de Boophilus microplus por Metarhizium anisopliae em pastagens infestadas artificialmente Control of Boophilus microplus larvae by Metarhizium anisopliae in artificially infested pastures

O objetivo deste trabalho foi avaliar a eficiência do controle exercido por Metarhizium anisopliae na população de Boophilus microplus, em pastagens de Brachiaria brizantha, e do híbrido Tifton 85 (Cynodon spp.), artificialmente infestadas com fêmeas ingurgitadas do carrapato. Trinta canteiros com 1 m² de área cada foram distribuídos aleatoriamente. Quinze foram pulverizados com esporos do fungo e quinze controles em cada forrageira, constituindo cinco repetições de cada tratamento, foram infestados com número e peso padronizados de fêmeas ingurgitadas do ácaro. Aplicou-se o fungo, na concentração de 1,8x10(8) conídios mL-1, em três situações: pulverização antes da infestação com o carrapato, após a infestação e posterioriormente à emergência das primeiras larvas nos capins. A ação do fungo foi avaliada no 35º, 38º, 41º, 48º, 55º e 61º dia pós-infestação, por meio da contagem de larvas recuperadas. Obteve-se controle de larvas do ácaro, que, nas avaliações realizadas entre o 35º e o 48º dia pós-infestação, variou entre 87% e 94%. As médias das contagens de estágios larvares do carrapato foram menores em todas as amostragens realizadas no capim-Tifton 85, indicando que houve efeito da pastagem na ação do fungo. A situação de aplicação influencia a atividade do fungo, com melhor resultado nas coletas realizadas entre o 41º e 55º dia após infestação em B. brizantha, e aplicação dos conídios logo após a emergência das primeiras larvas.<br>The objective of this work was to evaluate the efficiency of Metarhizium anisopliae fungus against Boophilus microplus population in Brachiaria brizantha and Tifton 85 (Cynodon) pastures, artificially infested with tick engorged females. Thirty plots of 1 m² each were randomly distributed in fifteen treated and fifteen control groups per type of grass, establishing five repetitions for each treatment. Pastures were infested with engorged tick females standardized by number and weight. Metarhizium anisopliae suspension with 1.8x10(8) conidia mL-1 concentration was sprayed on the plot in three different assays, prior infested with tick females, immediately after tick inoculation and at first larvae emergency. The fungus action was evaluated at 35th, 38th, 41st, 48th, 55th and 61st day post infestation by counting recovered larvae. A significative reduction of larvae counts occurred in fungus treated groups during 35th to 48th day post infestation, ranging between 87% and 94% of efficacy on tick larvae control. The mean values for larvae counting in Tifton 85 pasture were lower than in B. brizantha plot in all analysis, suggesting the pasture effect on fungus action. Treatment strategy influenced on M. anisopliae activity, which demonstrated better results at 41st and 55th day post infestation in B. brizantha, submitted to conidia challenge after larvae emergency