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

More documents

Recommendations

Info

Chapter 8 195(±)-N-1-(2-Octyl)-2-thiol-imidazole (±)-53a:Synthetic method 7.18,84% yield;1H NMR (200 MHz, CDCl 3 ) δ= 0.82 (t, J = 7.0 Hz, 3H), 1.25 (m,8H), 1.33 (d, J = 7.0 Hz, 3H), 1.70 (m, 2H), 4.92 (m, J = 7.0 Hz,1H), 6.69 (s, 1H), 6.75 (s, 1H), 11.40 (br s, 1H, exchangeable withD 2 O).IR (CHCl 3 ) ν cm-1 = 2580;M.P.= 84-85 °C (Et 2 O).Elementary Analysis. calcd. for C 11 H 20 N 2 S: C, 62.21; H, 9.49; N,13.19. Found: C, 62.41; H, 9.53; N, 13.25.(S)-(-)-N-1-(2-Octyl)-2-tiol-imidazole (S)-(-)-53a:Synthetic method 7.18[α] 20 D -35.6 (c 0.45, CHCl 3 ).Physical and spectral data were identical to those described above forthe racemate (±)-53a.(±)-N-1-(1-Phenylethyl)-2-thiol-imidazole-(±)-53b:Synthetic method 7.18, 84% yield;1H-NMR (200 MHz, CDCl 3 ) δ =1.74 (d, J = 7.4 Hz, 3H), 6.20 (q, J =7.4 Hz, 1H), 6.58 (s, 1H), 6.70 (s, 1H), 7.32 (m, 5H), 11.93 (br s,1H, exchangeable with D 2 O).IR (CHCl 3 ) ν cm-1 = 2585;M.P.=124-127 °C (Et 2 O).Elementary Analysis. calcd.for C 11 H 12 N 2 S: C, 64.66; H, 5.92; N,13.72. Found: C, 64.52; H, 5.88; N, 13.80.(S)-(-)-N-1-(1-Phenylethyl)-2-thiol-imidazole (S)-(-)-53b:Synthetic method 7.18[α] 20 D -239.2 (c 4.10, CHCl 3 ).Physical and spectral data were identical to those described above forthe racemate (±)-53b(±)-N-1-Phenyl-1-ethyl imidazole (±)-54:Synthetic method 7.191H-NMR (200 MHz, CDCl 3 ) δ =1.87 (d, J = 8.0 Hz, 3H), 5.34 (q, J =8.0 Hz, 1H), 6.90 (s, 1H), 7.08 (s, 1H), 7.14 (m, 2H), 7.30 (m, 3H),7.58 (s, 1H).M.P. =yellow oil.Anal. Calcd for C 11 H 12 N 2 : C, 76.71; H, 7.03; N, 16.27. Found: C,76.86; H, 7.10; N, 16.04.
Chapter 8 196(S)-(+)-1-Phenyl-1-ethyl imidazole (S)-(+)-54:Synthetic method 7.19[α] 20 D +5.20 (c 3.84, CHCl 3 ). e.e. > 98%.Physical and spectral data were identical to those described above forthe racemate (±)-54.(±)-55a:Synthetic method 7.20.11H-NMR (200 MHz, CDCl 3 ) δ = 4.95 (s 1H), 7.14-7.27 (m 14H).IR (CHCl 3 ) ν cm-1 = 2120;MP: Oil(±)-55b:Synthetic method 7.20.1 or 7.20.21H-NMR (200 MHz, CDCl 3 ) δ = 6.1 (s1H),7.13-7.29 (m3H), 7.31-7.59 (m10H).IR (CHCl 3 ): ν cm = 2105 cm -1 ;MP: Oil(±)-55c:Synthetic method 7.20.1 or 7.20.21H-NMR (200 MHz, CDCl 3 ) δ = 5.34 (s1H), 6.25 (s1H), 7.23-7.30(m 3H), 7.41-7.60 (m 6H).IR (CHCl 3 ) ν cm-1 = 2105;MP: Oil(±)-55d:Synthetic method 7.20.1 or 7.20.21H-NMR (200 MHz, CDCl 3 ) δ = 6.22 (s 1H), 6.58 (s 1H), 7.17- 7.39(m 3H), 7.43-7.54 (m 4H).IR (CHCl 3 ) ν cm-1 = 2125;MP: Oil(+)-55d:Synthetic method 7.20.2[α] 20 D = +0.5 (c 4, CHCl 3 ). e.e. NDPhysical and spectral data were identical to those described above forthe racemate (±)-55d.(±)-56aSynthetic method 7.21.1 or 7.21.21H-NMR (200 MHz, CDCl 3 ) δ = 1.98 (s 2H), 5.38 (s 1H), 7.28-7.55(m14H).
Page 1 and 2:
Advances in the stereoselectivesynt
Page 3:
ACKNOWLEDGMENT:I would like to than
Page 6 and 7:
Summary:Numerous drugs are chiral,
Page 8 and 9:
IndexII2.2 Synthesis of enantiopure
Page 10 and 11:
IndexIV4.4. Stereochemical Assignme
Page 12 and 13:
IndexVImethyl amine 69 1446.6. Stud
Page 14 and 15:
IndexVIII8.23.3.1 Desilylation usin
Page 16 and 17:
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
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
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
Page 42 and 43:
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
Page 72 and 73:
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
Page 78 and 79:
Chapter 2 63A -+ ROHRO - + AH'RO 2
Page 80 and 81:
Chapter 2 65There are various effec
Page 82 and 83:
Chapter 2 67The reactions were foun
Page 84 and 85:
Chapter 2 69Yamanaka and coworkers
Page 86 and 87:
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
Page 120 and 121:
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
Page 126 and 127:
Chapter 4 111which was eliminated e
Page 128 and 129:
Chapter 4 113separate (±)-57a and
Page 130 and 131:
Chapter 5 115to avoid this side rea
Page 132 and 133:
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
Page 138 and 139:
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
Page 144 and 145:
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 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 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
show all

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

Create successful ePaper yourself

Delete template?

Save as template?