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

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Chapter 9 21768) Brodie, A.M.H. in Design of Enzyme Inhibitors as Drugs , 198916, 505.69) McGuire, W. L. in Hormones and Cancer; Iacobelli, S. Ed.; RavenPress, York, 1980, Vol. 15, pp. 337-344.70) Siiteri, P. K.; Williams, J. E.; Takaki, N. K. J. Steroid Biochem.1976, 7, 897.71) Kirschener, M. A.; Schneider, G.; Ertel, N. H.; Worton, E. CancerResearch 1982, 42s, 3281s.72) Thompson, E.A.; Siiteri, P.K. J.Biol. Chem. 1974, 249, 5373.73) Aktar, M.; Wright, J.N. Natural Product Report 1991, 8, 527.74) Santen, R.J. Steroids 1977, 50, 575.75) Brodie, A.M.H.; Wing, L.Y.; Goss, P.; Dowsett, M.; Coombes,R.C. J. Steroid Biochem. 1986, 25, 859.76) Brodie, A.M.H.; Coombes, R.C.; Dowsett, M. J. Steroid Biochem.1987, 27, 899.77) Banting, L.; Nicholls, P.J.; Shaw, M.A.; Smith, H.J. in Progress inMedicinal Chemistry; Ellis, G.P. and West. G.B. Ed.; ElsevierScience B.V.; Amsterdam, 1989, Vol.26, pp.253-298.78) Brodie, A.M.H.; Banks, P.K.; Inkster, S.E.; Dowsett, M.; Coombes,R.C. J. Steroid Biochem. 1990, 37, 327.79) Brodie, A.M.H.; Banks, P.K.; Inkster, S.E.; Son, C.; Koos, R.D.J. Steroid Biochem. 1990, 37, 1043.80) Dowsett, M. J. Steroid Biochem.Molec. Biol. 1990, 37, 1037.81) Dowsett, M. J. Steroid Biochem.Molec. Biol. 1991, 39, 805.82) Brodie, A.M.H. Pharmac. Ther. 1993, 60, 501.83) Brodie, A.M.H. J. Steroid Biochem.Molec. Biol. 1994, 49, 281.84) Brodie, A.M.H.; Yue, W. in Sex Hormones and Antohormones inEndocrine Dependent Pathology: Basic and Clinical Aspects;Motta, M. and Serio, M. Ed. Elsevier Science B.V.; Amsterdam,1994, pp.279-286.85) Henderson, D.; Habenicht, U.F.; Nishino, Y.; Kerb, U.; El Eltreby,M.F. J. Steroid Biochem. 1986, 25, 867.86) Henderson, D.; Habenicht, U.F.; Nishino, Y.; Kerb, U.; El Eltreby,M.F. Steroids, 1987, 50, 219.87) Henderson, D. J. Steroid Biochem. 1987, 27, 905.88) Inkster, S.E.; Brodie, A.M.H. J. Clin. Metab. 1991, 73, 717.
Chapter 9 21889) Brodie, A.M.H.; Inkster, S.E. J. Steroid Biochem.Molec. Biol.1993, 44, 549.90) Longcope, C.; Pratt, J.H.; Schneider, S.H.; Fineberg, S.E. J. Clin.Endocrin. Metab.1974, 46, 146.91) Hemsell, D.L.; Grodin, J.; Breuner, P.F.; Siiteri, P.K.; MacDonald,P.C. J. Clin. Endocrin. Metab. 1974, 38, 476.92) Akhtar, M.; Colder, M.R.; Corina, D.L.; Wright, J.N. Biochem. J.1982, 201, 569.93) Covey, D.F.; Hood, H.F. Cancer Research 1982, 42s, 3327s.94) Caspi, E.; Arunachalam, T.; Nelson, P.A.; J. Am. Chem. Soc.1986, 108, 1847.95) Stevenson, D.E.; Wright, N.J.; Akhtar, M. J. Am. Chem. Soc.1985, 1078.96) Caspi, E.; Arunachalam, T.; Nelson, P.A.; J. Am. Chem. Soc.1986, 108, 1847.97) Hosoda, H.; Fishman, J. J. Am. Chem. Soc. 1974, 96, 7325.98) Goto,J.; Fishman, J. Science (Washington, D.C.), 1977, 195, 80.99) Fishman, J.; Raju, M.S. J. Biol. Chem. 1981, 256, 4472.100) Hahn, E.F.; Fishman, J. J. Biol. Chem. 1984, 259, 1689.101) Cole, P.A.; Robinson, C.H. J. Am. Chem. Soc. 1988, 110, 1284.102) Covey, D.F. in Sterol Biosynthesis Inhibition; Berg, D. andPlempel, M. Ed.; Ellis Horwood: Chichester, UK, 1988, pp.534-571.103) Watanabe, Y.; Ishimura, J. Am. Chem. Soc. 1989, 111, 8047.104) Cole, P.A.; Robinson, C.H. J. Med. Chem. 1990, 33, 2933.105) Cole, P.A.; Robinson, C.H. J. Am. Chem. Soc. 1991, 113, 8130.106) Caspi, E.; Dharmaratne, H.R.W.; Roitman, E.; Shackleton, C.J. Chem. Soc. Perkin Trans. 1, 1993, 1191.107) Korzekwa, K.R.; Trager, W.F.; Mancewicz, J.; Osawa, Y. J.Steroid Biochem.Molec. Biol. 1993, 44, 367.108) Lombardi, P. Current Pharmaceutical Design, 1995,1, 23-50.109) Schwarzel, W. C.; Kruggel, W. and Brodie, H. J. ‚ Endocrinology1973, 92, 866-880.110) Brodie, A. M. H.; Schwarzel, W. C. and Brodie, H. J. J. Steroid.Biochem. 1976, 7, 787-793.111) Brodie, A. M. H.; Wu, J. T.; Marsh, D. H.; and Brodie, H. J. Biol.Reprod. 1978, 18, 365-370.
Page 1 and 2:
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
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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
Page 28 and 29:
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
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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+
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Chapter 2 552.2.4 Lipases.Most lipa
Page 72 and 73:
Chapter 2 57enzyme intermediate can
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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
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Chapter 2 69Yamanaka and coworkers
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Chapter 2 71sodium or potassium car
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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
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Chapter 4 97NCO 2 HNCO 2 H(±)34c(-
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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
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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
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Chapter 6 133HCuSO 4 .5H 2 O,NH 4 O
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Chapter 6 1356.2.1 Heteroannullatio
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Chapter 6 137This discovery allowed
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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
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Chapter 6 145afforded the benzo[b]f
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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
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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)
Page 182 and 183: Chapter 8 167for 48 h. After coolin
Page 184 and 185: 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 234 and 235: Chapter 9 219112) Brodie, A. M. H.;
Page 236 and 237: Chapter 9 2214) Karabatsos, M.C. J.
Page 238 and 239: Chapter 9 22334c) Blow D. Nature 19
Page 240 and 241: Chapter 9 22567a) Kundu, N.G.; Pal,
Page 242: Chapter 9 22712) Thompson,A.S.; Hum
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