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

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Chapter 8 187Synthetic method 7.7.1[α] 20 D +58.8 (c 0.85, CHCl 3 ).Physical and spectral data were identical with those described abovefor the racemate (±)-33d.(R,S)-(±)-1-(1-Phenyl-1-propyl)imidazole-4,5-dicarbonitrile (±)-33eSynthetic method 7.7.1Purified by flash chromatography (n-hexane/AcOEt 2:1 ). Ananalytical sample was obtained by preparative TLC.1H NMR (200 MHz, CDCl 3 ) δ= 1.05 (t, J = 7.4 Hz, 3H), 2.38(quintet, J = 7.4 Hz, 2H), 5.23 (t, J = 7.4 Hz, 1H), 7.28 (m, 2H), 7.38(m, 3H), 7.88 (s, 1H).IR (CHCl 3 ): ν cm-1= 2250 cm -1 ;M.P.= Colorless oil.Elementary Analysis. calcd. for C 14 H 12 N 4 : C, 71.17; H, 5.12; N,23.71. Found: C, 71.38; H, 5.20; N, 23.42.(S)-(-)-1-(1-Phenyl-1-propyl)imidazole-4,5-dicarbonitrile(S)-(-)-33eSynthetic method 7.7.1[α] 20 D -44.3 (c 2.82, CHCl 3 ).Physical and spectral data were identical with those described abovefor the racemate (±)-33e.1-(_-Phenylbenzyl)imidazole-4,5-dicarbonitrile 33fSynthetic method 7.7.2Purified by flash chromatography (n-hexane/AcOEt 2:1) followedby recrystallization from Et 2 O.1H NMR (200 MHz, CDCl 3 ) δ = 6.70 (s, 1H), 7.13 (m, 4H), 7.43 (m,7H).IR (CHCl 3 ): ν cm-1= 2240 cm -1M.P.= mp 137-138 °C.Elementary Analysis. calcd. for C 18 H 12 N 4 : C, 76.04; H, 4.25; N,19.71. Found: C, 76.24; H, 4.18; N, 19.58.(±)-1-[_-(4-Biphenyl)benzyl]imidazole-4,5-dicarbonitrile(±)-33gSynthetic method 7.7.2.Purified by flash chromatography (n-hexane/AcOEt 5:1 to 3:1). Ananalytical sample was prepared by recrystallization from Et 2 O.
Chapter 8 1881H-NMR (200 MHz, CDCl 3 ) δ = 6.74 (s, 1H), 7.45 (m, 4H), 7.6 (m,11H).IR (CHCl 3 ): ν cm-1= 2225 cm -1 .M.P.= 58-59 °C.Elementary Analysis. calcd. for C 24 H 16 N 4 : C, 79.98; H, 4.47; N,15.54. Found: C, 80.12; H, 4.39; N, 15.49.(R,S)-(±)-1-[_-(2-Bromophenyl)benzyl]imidazole-4,5-dicarbonitrile (±)-33hSynthetic method 7.7.2Purified by flash chromatography (n-hexane/AcOEt 2:1) followed byrecrystallization from methanol.1H-NMR (200 MHz, CDCl 3 ) δ = 6.82 (dd, J = 5.7, 2.0 Hz, 1H), 7.05(s, 1H), 7.10 (m, 2H), 7.38 (m, 3H), 7.45 (m, 3H), 7.70 (dd, J = 5.7,2.0 Hz, 1H).IR (CHCl 3 ): ν cm-1= 2240 cm -1M.P.= 176-177 °C.Elementary Analysis. calcd. for C 18 H 11 BrN 4 : C, 59.52; H, 3.05; N,15.43. Found: C, 59.43; H, 3.12; N, 15.58.(R,S)-(±)-1-[_-(2-Bromophenyl)-4-phenylbenzyl]imidazole-4,5-dicarbonitrile (±)-33iSynthetic method 7.7.2.Purified by flash chromatography (n-hexane/AcOEt 3:1) followed byrecrystallization from MeOH.1H=NMR (200 MHz, CDCl 3 ) δ = 6.89 (dd, J = 6.0, 1.8 Hz, 1H), 7.06(s, 1H), 7.14 (d, J = 7.0 Hz, 2H), 7.41 (m, 6H), 7.65 (m, 5H).IR (CHCl 3 ): ν cm-1= 2230 cm -1M.P.= 169-171 °C.Elementary Analysis. calcd. for C 24 H 15 BrN 4 : C, 65.62; H, 3.44; N,12.75. Found: C, 65.80; H, 3.33; N, 12.91.(R,S)-(±)-1-{_-[2-Benzo(b)furan]-4-phenylbenzyl}imidazole-4,5-dicarbonitrile (±)-33 lSynthetic method 7.7.2.Purified by flash chromatography (n-hexane/AcOEt 2:1) 1 H-NMR (200MHz, CDCl 3 ) δ = 6.68 (s 1H), 6.77 (s1H), 7.47-7.21 (m 8H),7.55 (1H d, J =6.1Hz), 7.68 (s1H).IR (CHCl 3 ): ν cm-1= 2220 cm -1
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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
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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
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 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 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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