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

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Chapter 8 181IR (CHCl 3 ): ν cm-1= 1675,1600,1560.GC-MS = 291 M + (100%)M.P.= 96-97 °C.4'-Fluorophenyl-2-benzo[b]furanone 26d:Synthetic procedure 7.2.1.1H-NMR (300 MHz; CDCl 3 ) δ =7.99-7.92 (m 2H), 7.56 (d 1H8.5Hz) 7.50 (m3H), 7.20-7.00 (m 3H).IR (CHCl 3 ): ν cm-1= 1685,1600,1550.GC-MS = 240 M + (100%)M.P.= 145-147°C.4'-Chlorophenyl-2-benzo[b]furanone 26e:Synthetic procedure 7.2.1.1H-NMR (300 MHz; CDCl 3 ) δ =8.03 (d 2H, 9.2 Hz), 7.75-7.61 (m2H), 7.55-7.38 (m4H), 7.37-7.30 (m 1H).IR (CHCl 3 ): ν cm-1= 1680,1595,1540.GC-MS = 256 M + (100%)M.P.= 152-153°C.(±)-4-Phenyl benzhydrol (±)-27a:Synthetic procedure 7.3.1.or 7.6.1 or 7.6.2.1H-NMR (300 MHz; CDCl 3 ) δ =7.64 (m;3H), 7.50 (m, 9H), 7.32(m,2H), 5.85 (s,1H), 2.45 (s,1H).IR (CHCl 3 ): ν cm-1= 3380, 1605, 1295.GC-MS = 260 M + (58%), 243 M-OH (100%).M.P. = 115-117°C.(±)-2-Bromobenzhydrol (±)-27b:Synthetic procedure 7.3.1.1H-NMR (200 MHz; CDCl 3 ) δ =7.59 (1H), 7.53 (1H), 7.40 (2H),7.33(3H), 7.27 (1H), 7.15 (1H), 6.19 (1H, d 3.7 Hz), 2.41 (1H,d 3.7 Hz).IR (CHCl 3 ): ν cm-1= 3375, 1580, 1325.GC-MS: 262 M + (76%), 246 M-OH (100%)M.P = 58-59 °C.(+)-2-Bromo-benzhydrol (+)-27b:Synthetic procedure 7.5.1[α] 20 D +46.6 (c 1.30, acetone). e.e. >95 %.Absolute stereochemistry not determinated.
Chapter 8 182Physical and spectral data were identical with those described abovefor the racemate (±)-27b.(±)-2-Bromo-4'-phenyl benzhydrol (±)-27c:Synthetic procedure 7.3.1.1H-NMR (200 MHz; CDCl 3 ) δ =7.48 (m,13 H), 6.24 (s, 1H), 2.44 (s,1 H).IR (CHCl 3 ): ν cm-1= 3365,1530,1350.GC-MS: 339 M + (68%), 322 M-OH (100%).M.P. = 101-103 °C.Anal. Calcd for C 19 H 15 BrO: C, 67.27; H, 4.46. Found: C, 67.35; H,4.40.(+)-2-Bromo-4'-phenylbenzhydrol (+)-27c.Synthetic procedure 7.5.1[α] 20 D +65.4 (c 2.60, CHCl 3 ).e.e.>95 % HPLC: chiracel OD n-hexane/EtOH 90:20; 1 ml/min. rt=9.92 min (+)-27c; 13.44 min (-)-27c.Absolute stereochemistry not determinated.Physical and spectral data were identical with those described abovefor the racemate (±)-27c.(±)-2-Fluoro-4'-phenyl benzhydrol (±)-27d:Synthetic procedure 7.3.1.1H-NMR (200 MHz; CDCl 3 ) δ = 7.85 (d 2H,8.5 Hz), 7.75-7.45 (m8H), 7.35-7.10 (m 3H), 6.35 (s 1H), 2.48 (s 1H).MP=oil(+)-2-Fluoro-4'-phenylbenzhydrol (+)-27d:Synthetic procedure 7.5.1[α] 20 D +58.4 (c 2.35, CHCl 3 ).e.e.>95 % HPLC: chiracel OD n-hexane/EtOH 90:20; 1 ml/min. rt=8.52(+)-27d; 12.44 (-)-27d.Absolute stereochemistry not determinated.Physical and spectral data were identical with those described abovefor the racemate (±)-27d.(±)-4-Nitro-4'-phenyl benzhydrole (±)-27e:Synthetic procedure 7.3.1.1H-NMR (200 MHz; CDCl 3 ) δ= 7.85 (d, 2H, 9.1Hz), 7.50 (m, 11 H),5.95 (s1H), 2.60 (s, 1H).IR (CHCl 3 ): ν cm-1= 3375, 1515, 1340.
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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
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Chapter 1 3The concept of stereoche
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Chapter 1 5switches is in the area
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Chapter 1 7-bonds 9 . It is now wid
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Chapter 1 914CH 3Cyt P-450 DMOH3O 2
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Chapter 1 11piperazine) is also the
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Chapter 1 13The four stereoisomers
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Chapter 1 15single enantiomers and
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Chapter 1 17was synthesized by the
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Chapter 1 19HOHODesmolaseHOCholeste
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Chapter 1 21formic acid results in
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Chapter 1 23inactivation. 113 . Bec
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Chapter 1 25Two newer compounds whi
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Chapter 1 2715 is an advanced repre
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Chapter 1 29transformation of the a
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Chapter 1 31Enantioselective synthe
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Chapter 1 33+R,S DRUG ANCHOR R MOLE
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Chapter 1 35solubilized in hot etha
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Chapter 2 37RsORmRmRsRLRL RRRLH - A
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Chapter 2 39The stereochemistry and
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Chapter 2 41An asymmetric reducing
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Chapter 2 43This approach clearly e
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Chapter 2 45PhaxeqP 1MP 2axeqPhP 2M
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Chapter 2 47pyrrolidine ] 20 , LAH-
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Chapter 2 49Enzymatic reactions are
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Chapter 2 51As [ES] in equation 4 c
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Chapter 2 53E+AK 1AK -1AEAK 2AE+PE+
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Chapter 2 552.2.4 Lipases.Most lipa
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Chapter 2 57enzyme intermediate can
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Chapter 2 59projecting above the pl
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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
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Chapter 3 75literature as the best
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Chapter 3 77dry solvents and, is ch
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Chapter 3 79XXOH+ H 2 NDry K 2 CO 3
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Chapter 3 81substituents are the mo
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Chapter 3 83induces a rotation of t
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Chapter 3 85very sharp and it was p
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Chapter 3 87Raney NickelOH Br MeOH;
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Chapter 4 8933a-m were hydrolysed t
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Chapter 4 91benzo[b]furane (entries
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Chapter 4 93hydroxy or amine groups
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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(+)
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Chapter 4 101As already outlined ab
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Chapter 4 103(+)-(S)-2-octylimidazo
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Chapter 4 105CNNH N2 NCN nC 6 H 13N
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Chapter 4 107key step is the conver
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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
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Chapter 5 115to avoid this side rea
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Chapter 5 117Complete degradation o
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Chapter 5 119Entry R T °C Product
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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
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Chapter 5 127experiments. But it wa
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Chapter 5 129OClOSAM IIPH=7; R.T.OH
Page 146 and 147: 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
Page 152 and 153: Chapter 6 137This discovery allowed
Page 154 and 155: Chapter 6 139OH(±)-62OHFigure 6.1
Page 156 and 157: Chapter 6 141Entry Substrate R Time
Page 158 and 159: 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
Page 164 and 165: Chapter 6 149H2-IodophenolOHOH(±)-
Page 166 and 167: Chapter 6 151presence of base as de
Page 168 and 169: 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
Page 176 and 177: Chapter 8 16145 min, the mixture wa
Page 178 and 179: 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 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 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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