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

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IndexVIII8.23.3.1 Desilylation using KF 1708.23.3.2 Desilylation using TBAF in dry THF 1708.23.3.3 Desilylation using K 2 CO 3 in MeOH 1718.23.4 Synthesis of (±)-58a by addition of magnesiummethynyl halide to benzaldehyde 1718.24 Screening of lipases for the esterification of arylpropynols 1718.24.1 General screening procedure 1718.25 Synthesis of 1-aryl-2-propyn-1-ol acetate 1728.25.1 General method a 1728.25.2 General method b 1728.26 Screening of lipases and reaction conditions for thehydrolysis of arylpropynol acetates (±)-60 1738.26.1 General procedure for the screening of lipases 1738.26.2 Cosolvent effect on the hydrolysis of arylpropynolsacetates (±)-60 by SAMII lipase 1738.26.3 Temperature effect on the hydrolysis ofarylpropynol acetates (±)-60 in presence ofSAMII lipase 1738.27 Synthesis of 1-aryl-2-propyn-1-ol chloroacetate (±)-611748.28 Enzymatic resolution of chloroacetates (±)-61 b-c,e,h-l1748.28.1 General procedure 1748.29 Hydrolysis of enantiopure acetate (S)-60 and8.30 chloroacetate (S)-61 1758.30 Synthesis of Aryl-2-benzo[b]furanyl carbinoles 27g,land 63a-d in racemic and enantiopure form via palladiumcatalyzedheteroannulation (general procedure) 1758.31 Synthesis of aryl benzo[b]furan carbinol by basecatalyzed 5-endotrig cyclization 1768.31.1 Synthesis of phenyl-2benzo[b]furanyl carbinol(±)-27g by base catalyzed 5-endotrig cyclization 1768.31.2 Cyclization of 1-phenyl-3-(2'acetoxyphenyl)-2-propyn-1-ol (±)71 to phenyl-2benzo[b]furanyl carbinol (±)-2 bybasic catalyzed 5-endotrig cyclization 176
IndexIX8.32 Synthesis of racemic 1-phenyl-3-(2'aminophenyl)-2-propyn-1-ol (±)-65 1778.33 Synthesis of N-Mesyl-2-iodoaniline 46 1778.34 Synthesis of Aryl 2-(N-mesyl)-indolyl carbinols 64a-gin racemic and enantiopure form via palladium-catalyzedheteroannulation of arylpropagylic alcohols 58 (generalprocedure) 1778.35 Synthesis of (2'-Hydroxyphenyl)-2-propyn-1-phenyl-1-ol (±)-62 1788.36 Synthesis of racemic 1-Phenyl-3-(2'acetoxyphenyl)-2-propyn-1-ole (±)-71 1788.37 Analytical data 179Chapter 9:9 References 213
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 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
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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 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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