Advances in the stereoselective synthesis of antifungal agents and ...

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Chapter 9 22334c) Blow D. Nature 1991, 351, 444.36a) Dijkstra, B.W. et al; J. Mol. Biol. 1981, 147, 97.36b) Scott, D.L.; White, S.P.; Otwiinowski, Z.; Yuan, W.; Gelb, M.H.;Siegler, P.B. Science 1990, 250, 1541.37) Brzozowski, A.M.; Derewenda, Z.S.; Derewenda, U.; Dodson, G.;Lawson, D.M.; Turkenburg, J..; Bjorking, F.; Huge-Jensen, B.;Phtakar, S.A.; Thim, L. Nature 1991, 351, 491.38a) Tambo, G.M.R.; Schar,H.P.; Busquets, X.F.; Gisobba,O.Tetrahedron Lett. 1986, 27, 5707.38b) Stokes, T.M.; Oehlslager, A.C. Tetrahedron Lett. 1987, 28, 2091.38c) Francaloni, F.; Cesti,P.; Cabri, W.; Bianchi, D.; Martinago, T.;Foa', M. J. Org. Chem. 1987, 52, 5079.39a) Costaing, M.D.; Jeso, B.D.; Drouillard, S..;Maillard, B.Tetrahedron Lett. 1987, 28,953.38b) Sweers, H.M.Wang, C.H. J. Am. Chem. Soc. 1986, 108, 6421.38c) Wang, Y.F.; Wang, C.H. J. Org. Chem. 1988, 53, 117.39) Chen, C.S.; Wu, S.H.; Girdaukas, G.; Sih, C. J. Am. Chem. Soc.1987, 109, 2812.40) Kazlausaskas, R.J.; Weissfloch, A.N.E.; Rappaport, A.T.; Cuccia,L.A. J. Org. Chem. 1991, 56, 2656.41) Toone,J.E.; Werth, M.J.; Jones, J.B. J. Am. Chem. Soc. 1990,112,4946.42) Burgess, K.; Jennings,L.D. J. Am. Chem. Soc. 1991, 113, 6129.43) Laumen, K.; Schneider, M.P. J. Chem. Soc. Chem. Commun.1988,598.44) Laumen, K.; Breitgoff, D.; Seemayer, R.; Schneider, M.P. J.Chem. Soc. Chem. Commun. 1989,148.45) Almisick,A.; Buddrus,J.; Honicke-Schmidt, P.; Laumen, K.;Schneider, M.P. J. Chem. Soc. Chem. Commun. 1989,1391.46) Ader, U.; Breitgoff, D.; Klein, P.; Laumen,K.E.; Schneider, M.P.Tetraedron Lett. 1989, 30, 1793.47) Laumen, K.; Seemayer, R.; Schneider, M.P. J. Chem. Soc. Chem.Commun. 1990,49.48) Klostermann, M.; Rierkeis,J.G.T.; Boesten, N.J.H.; Zeegers, H.J.MJ. Org. Chem. in press.49) Burgess, K.; Jennings, L.D. J. Am. Chem. Soc. 1990, 112, 7434.50) O'Hagan,D.; Zaidi,A.N. Tetrahedron: Asymmetry, 1994,5, 1111.
Chapter 9 22451) Mitsunobu, O.; Yamada, M. Bull. Chem. Soc. Jpn., 1967, 40,2380.52) Mitsunobu, O.Synthesis 1981, 1.53a) Camp, D.; Hanson, G.R.; Jenkins, I.D.J. Org. Chem. 1995, 60,2977.53b) Crich, D.; Dyker, H.; Harris, R.J. J. Org. Chem. 1989, 54, 257.53c) Patuard-Copper, A.; Evans Jr, S.A. J. Org. Chem. 1989, 54, 2485.53d) Hughes, D.L.; Reamer, R.A.; Bergan, J.J.; Grabowski E. J.J. J. Am.Chem. Soc. 1988, 110, 6487.54) Morrison, D.C. J. Org. Chem. 1958, 23, 1072.55) Brunn, E.; Huisgen, R. Angew.Chemie.Int.Ed.Engl. 1969, 8, 513.56) Camp, D.; Jenkins, I.D.J. Org. Chem. 1989, 54, 3045.57) Kato, K.; Mitsunobu, O. J. Org. Chem. 1970, 35, 422758) Camp, D.; Hanson, G.R.; Jenkins, I.D.J. Org. Chem. 1995, 60,2977.59) Kunz, H.; Schmidt, P.; Justus Liebigs Ann. Chem. 1982, 1245.60) Tsunoda, T.; Yamaniya, Y.; Ito, S. Tetrahedron Lett. 1993, 34,1639.61) Dodge, J.A.; Trujello, J.I.; Presnell, M. J. Org. Chem. 1994, 59,234.62a) Castro, C.E.; Stephens, R.D. J. Org. Chem. 1963, 28, 2163.62b) Castro, C.E.; Stephens, R.D. J. Org. Chem. 1963, 28, 3313.62c) Castro, C.E.; Gaughan, E.J.; Owsley, D.C. J. Org. Chem. 1966,31, 4071.62d) Castro, C. E.; Havlin, R.; Honwad, V.K.; Malte, A.; Steve Moje'J. Am. Chem. Soc. 1969, 91, 23, 6464.63) Yang, Z.; Liu, H.B.; Lee, C.M.; Chang, H.M.; Wong, H.N.C. J.Org. Chem. 1992, 57, 7248.64) Doead, G.J.S.; Barltrop, J.A.; Petty, C.M.; Owen, T.C.Tetrahedron Lett. 1989, 30, 13, 1597.65a) Sakamoto, T.; Kondo, Y.; Yamanaka, H. Chem. Pharm. Bull.1986, 34, 6, 2362.65b) Sakamoto, T.; Kondo, Y.; Iwashita, S.; Yamanaka, H. Chem.Pharm. Bull. 1987, 35, (5), 1823.65c) Sakamoto, T.; Kondo, Y.; Iwashita, S.; Nagano, T.; Yamanaka, H.Chem. Pharm. Bull. 1988, 36, 4, 1305.66) Cacchi, S.; Arcadi, A.; Marinelli, F. Synthesis 1986, 749.
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Advances in the stereoselectivesynt
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ACKNOWLEDGMENT:I would like to than
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Summary:Numerous drugs are chiral,
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IndexII2.2 Synthesis of enantiopure
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IndexIV4.4. Stereochemical Assignme
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IndexVImethyl amine 69 1446.6. Stud
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IndexVIII8.23.3.1 Desilylation usin
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Chapter 1 11.Introduction1.1. Chira
Page 18 and 19:
Chapter 1 3The concept of stereoche
Page 20 and 21:
Chapter 1 5switches is in the area
Page 22 and 23:
Chapter 1 7-bonds 9 . It is now wid
Page 24 and 25:
Chapter 1 914CH 3Cyt P-450 DMOH3O 2
Page 26 and 27:
Chapter 1 11piperazine) is also the
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Chapter 1 13The four stereoisomers
Page 30 and 31:
Chapter 1 15single enantiomers and
Page 32 and 33:
Chapter 1 17was synthesized by the
Page 34 and 35:
Chapter 1 19HOHODesmolaseHOCholeste
Page 36 and 37:
Chapter 1 21formic acid results in
Page 38 and 39:
Chapter 1 23inactivation. 113 . Bec
Page 40 and 41:
Chapter 1 25Two newer compounds whi
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Chapter 1 2715 is an advanced repre
Page 44 and 45:
Chapter 1 29transformation of the a
Page 46 and 47:
Chapter 1 31Enantioselective synthe
Page 48 and 49:
Chapter 1 33+R,S DRUG ANCHOR R MOLE
Page 50 and 51:
Chapter 1 35solubilized in hot etha
Page 52 and 53:
Chapter 2 37RsORmRmRsRLRL RRRLH - A
Page 54 and 55:
Chapter 2 39The stereochemistry and
Page 56 and 57:
Chapter 2 41An asymmetric reducing
Page 58 and 59:
Chapter 2 43This approach clearly e
Page 60 and 61:
Chapter 2 45PhaxeqP 1MP 2axeqPhP 2M
Page 62 and 63:
Chapter 2 47pyrrolidine ] 20 , LAH-
Page 64 and 65:
Chapter 2 49Enzymatic reactions are
Page 66 and 67:
Chapter 2 51As [ES] in equation 4 c
Page 68 and 69:
Chapter 2 53E+AK 1AK -1AEAK 2AE+PE+
Page 70 and 71:
Chapter 2 552.2.4 Lipases.Most lipa
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Chapter 2 57enzyme intermediate can
Page 74 and 75:
Chapter 2 59projecting above the pl
Page 76 and 77:
Chapter 2 612.3.1.1. Step 1: Adduct
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Chapter 2 63A -+ ROHRO - + AH'RO 2
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Chapter 2 65There are various effec
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Chapter 2 67The reactions were foun
Page 84 and 85:
Chapter 2 69Yamanaka and coworkers
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Chapter 2 71sodium or potassium car
Page 88 and 89:
Chapter 3 73The reaction is quite s
Page 90 and 91:
Chapter 3 75literature as the best
Page 92 and 93:
Chapter 3 77dry solvents and, is ch
Page 94 and 95:
Chapter 3 79XXOH+ H 2 NDry K 2 CO 3
Page 96 and 97:
Chapter 3 81substituents are the mo
Page 98 and 99:
Chapter 3 83induces a rotation of t
Page 100 and 101:
Chapter 3 85very sharp and it was p
Page 102 and 103:
Chapter 3 87Raney NickelOH Br MeOH;
Page 104 and 105:
Chapter 4 8933a-m were hydrolysed t
Page 106 and 107:
Chapter 4 91benzo[b]furane (entries
Page 108 and 109:
Chapter 4 93hydroxy or amine groups
Page 110 and 111:
Chapter 4 95the products with ethyl
Page 112 and 113:
Chapter 4 97NCO 2 HNCO 2 H(±)34c(-
Page 114 and 115:
Chapter 4 99NNH37CO2EtOH(±)-27a(+)
Page 116 and 117:
Chapter 4 101As already outlined ab
Page 118 and 119:
Chapter 4 103(+)-(S)-2-octylimidazo
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Chapter 4 105CNNH N2 NCN nC 6 H 13N
Page 122 and 123:
Chapter 4 107key step is the conver
Page 124 and 125:
Chapter 4 109reverse addition in th
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Chapter 4 111which was eliminated e
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Chapter 4 113separate (±)-57a and
Page 130 and 131:
Chapter 5 115to avoid this side rea
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Chapter 5 117Complete degradation o
Page 134 and 135:
Chapter 5 119Entry R T °C Product
Page 136 and 137:
Chapter 5 1212:1:3 in weight. All t
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Chapter 5 123reaction conditions we
Page 140 and 141:
Chapter 5 125Entry Substrate R Time
Page 142 and 143:
Chapter 5 127experiments. But it wa
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Chapter 5 129OClOSAM IIPH=7; R.T.OH
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Chapter 5 131OHOXHOHRHK 2 CO 3 ; Me
Page 148 and 149:
Chapter 6 133HCuSO 4 .5H 2 O,NH 4 O
Page 150 and 151:
Chapter 6 1356.2.1 Heteroannullatio
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Chapter 6 137This discovery allowed
Page 154 and 155:
Chapter 6 139OH(±)-62OHFigure 6.1
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Chapter 6 141Entry Substrate R Time
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Chapter 6 143HOH58-a-c,e,h-lRPdCl 2
Page 160 and 161:
Chapter 6 145afforded the benzo[b]f
Page 162 and 163:
Chapter 6 147RR[P(Ph) 3 ]Pd°OHOPh
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Chapter 6 149H2-IodophenolOHOH(±)-
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Chapter 6 151presence of base as de
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Chapter 7 153A chiral lithium alumi
Page 170 and 171:
Chapter 7 155derivatives were tried
Page 172 and 173:
Chapter 7 157Finally an hypothesis
Page 174 and 175:
Chapter 8 159were washed with a sat
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Chapter 8 16145 min, the mixture wa
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Chapter 8 1638.9 Decarboxylation of
Page 180 and 181:
Chapter 8 165Alcohol 27a (0.2 mmol)
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Chapter 8 167for 48 h. After coolin
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Chapter 8 169room temperature for t
Page 186 and 187:
Chapter 8 171in CH 2 Cl 2 and washe
Page 188 and 189: Chapter 8 1738.26 Screening of lipa
Page 190 and 191: Chapter 8 175Na 2 SO 4 . After remo
Page 192 and 193: Chapter 8 177NMR and MS analysis we
Page 194 and 195: Chapter 8 179Argon was bubbled thru
Page 196 and 197: Chapter 8 181IR (CHCl 3 ): ν cm-1=
Page 198 and 199: Chapter 8 183GC-MS: 305 M + (68%),
Page 200 and 201: Chapter 8 185[α] 20 D -5.7 (c 1.75
Page 202 and 203: Chapter 8 187Synthetic method 7.7.1
Page 204 and 205: Chapter 8 189(R,S)-(±)-1-(2-Octyl)
Page 206 and 207: Chapter 8 191M.P. = oil.Elementary
Page 208 and 209: Chapter 8 193Synthetic method 7.11.
Page 210 and 211: Chapter 8 195(±)-N-1-(2-Octyl)-2-t
Page 212 and 213: Chapter 8 197IR (CHCl 3 ) ν cm-1 =
Page 214 and 215: Chapter 8 199(±)-1-(4-Fluorophenyl
Page 216 and 217: Chapter 8 201Physical and spectral
Page 218 and 219: Chapter 8 203(±)-1-(Phenyl)-2-prop
Page 220 and 221: Chapter 8 205128.61, 128.87, 130.39
Page 222 and 223: Chapter 8 207min.Physical and spect
Page 224 and 225: Chapter 8 20913C J MOD NMR (CDCl 3
Page 226 and 227: Chapter 8 211(±)-2'-Methylphenyl-2
Page 228 and 229: Chapter 9 213References chapter 1:1
Page 230 and 231: Chapter 9 21531) De Felice, R.; Joh
Page 232 and 233: Chapter 9 21768) Brodie, A.M.H. in
Page 234 and 235: Chapter 9 219112) Brodie, A. M. H.;
Page 236 and 237: Chapter 9 2214) Karabatsos, M.C. J.
Page 240 and 241: Chapter 9 22567a) Kundu, N.G.; Pal,
Page 242: Chapter 9 22712) Thompson,A.S.; Hum
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