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

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Chapter 8 207min.Physical and spectral data were identical to those described above forthe racemate (±)-63a.(±)-(3'-Methylphenyl)-2 benzo[b]furanyl carbinol (±)-63b:Synthetic method 7.30.1H NMR (CDCl3) δ= 2.39 (s,3H), 2.53 (d, 4.3 Hz, 1H), 5.93 (d, 4.3Hz, 1H), 6.57 (s, 1H), 7.32-7.18 (m,6H), 7.72-7.45 (m,2H).13C NMR ( CDCl 3) δ= 21.294, 70.509, 103.744, 111, 21 9, 121.000,122.664, 123.816, 124.075, 127.358, 128.003, 128.356, 128.957,138.136, 140.211, 154.980, 158.653.13C J MOD NMR (CDCl3) δ= (+)21.294, (+)70.509, (+)103.744,(+)111,219, (+)121.000, (+)122.664, (+)123.816, (+)124.075,(+)127.358, (-) 128.003, (+)128.356, (+)128.957, (-)138.136, (-)140.211, (-)154.980, (-) 158.653.GC-MS M + 238(100%), M + -OH 221.M.P: oil(R)-(-)-(3'-Methylphenyl)-2benzo[b]furanyl carbinol (R)-(-)-63b:Synthetic method 7.30.[α] 20 D -3.55, (c 2.81 CHCl 3 ), 98.11% ee (Chiracel OD n-hexane/isopropanole), (S)-(+)-2d rt= 15.38 min., (R)-(-)-2d rt =17.86 min.Physical and spectral data were identical to those described above forthe racemate (±)-63b.(±)-3'-Fluorophenyl-2 benzo[b]furanyl carbinol (±)-63c:Synthetic method 7.30.1H NMR (CDCl3) δ= 2.55 (d,4.2Hz,1H), 5.94 (d,4.2Hz,1H) 6.54(s,1H), 7.37-6.98 (m,4H), 7.53-7.40 (m, 3H).13C NMR (CDCl3) δ= 69.745d, 104.097, 111.233, 113.435, 113878,114.794, 115,215, 121.144, 122.236d, 124.390, 127.802, 130.014d,142.757d, 154.979, 157.728, 160.334, 165.226.13C J MOD (CDCl3) NMR (+)69.745d, (+)104.097, (+)111.233,(+)113.435, (+)113878, (+)114.794, (+)115,215, (+)121.144,(+)122.236d, (+)124.390, (-)127.802, (+)130.014d, (-)142.757d, (-)154.979, (-)157.728, (-)160.334, (-)165.226.GC-MS M+ 242(100%), M+ -OH 225.M.P: oil
Chapter 8 208(R)-(+)-3'-Fluorophenyl-2 benzo[b]furanyl carbinol (R)-(+)-63c:Synthetic method 7.30.[20D +6.23, (c 2.41 CHCl3) 98.50% ee (Chiracel OD n-hexane/isopropanole), (S)-(-)-2e rt=73.36 min., (R)-(+)-2ert=83.54 min.Physical and spectral data were identical to those described above forthe racemate (±) 63c.(±)-2'-Methylphenyl-2benzo[b]furanyl carbinole (±)-63d:Synthetic method 7.30.1H NMR (CDCl3) δ= 2.02 (s,1H), 2.48 (d,4.2Hz, 1H), 6.13 (d,4.2Hz,1H), 6.40 (s,1H), 7.27-7.15 (m, 5H), 7.57-7.42 (m,3H).13C NMR (CDCl 3 ) δ= 18.933, 67.475, 104.130, 111.253, 121.037,122.718, 124.184, 126.219, 126.380, 128.083, 130.445, 135.512,138.288, 155.036, 158.217.13C J MOD NMR (CDCl 3 ) δ= (+)18.933, (+)67.475, (+)104.130,(+)111.253, (+)121.037, (+)122.718, (+)124.184, (+)126.219,(+)126.380, (-) 128.013, (+)128.083, (+)130.445, (-)135.512, (-)138.288, (-)155.036, (-) 158.217.GC-MS M + 238(100%), M + -OH 221.M.P: oil(R)-(-)-2'-Methylphenyl-2-benzo[b]furanyl carbinol (R)- (-) 63d:Synthetic method 7.30.[α] 20 D -32.53, (c 1.076 CHCl 3 ) 93.26% ee (Chiracel OD n-hexane/isopropanole), (S)-(+)-2f rt=30.56 min., (R)-(-)-2frt=33.92 min.Physical and spectral data were identical to those described above forthe racemate (±) 63d.(±)-Phenyl-2-(N-mesyl)indolyl carbinol (±)-64a:Synthetic method 7.33:1H NMR (CDCl 3 ) δ= 3.02 (s,3H), 3.24 (d, 5.7 Hz,1H), 6.27 (s,1H),6.37 (d,5.7Hz,1H), 7.51-7.24 (m,8H), 7.98 (7.56Hz,1H).13C NMR (CDCl 3 ) δ= 40.772, 69.230, 111.256, 113.9912, 121.348,123.677, 125.083, 127.122, 128.097, 128.351, 128.568, 137.134,140.767, 143.037.
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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
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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
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 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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