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

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Chapter 8 183GC-MS: 305 M + (68%), 288 M-0H (100%).M.P. = 165-166 °C.(±)-3-Nitro-4'-phenyl benzhydrol (±)-27f:Synthetic procedure 7.3.1.1H-NMR (200 MHz; CDCl 3 ) δ =8.32 (s, 1H), 8.07 (d 1H, 9.1Hz),7.73 (d 1H, 7.6Hz), 7.42 (m, 10H), 5.95 (s 1H), 2.34 (s 1H).IR (CHCl 3 ): ν cm-1= 3380,1525,1335.GC-MS: 305 M + (78%), 288 M-OH (100%).M.P. = 143-144 °C.(±)-Phenyl-2-benzo[b]furanyl carbinol (±)-27g:Synthetic procedure 7.3.1. or 7.301H-NMR (200 MHz, CDCl 3 ) δ = 2.70 (d,1H), 5.92 (d,1H), 6.51(s,1H), 7.55-7.16 (m, 9H);13C-NMR (CDCl 3 ) δ = 70.514, 103.912, 111.241, 121.057, 122.735,124.191, 126.727, 127.969, 128.220, 128.477, 140.237, 155.010;158.484;13C-J MOD-NMR (CDCl 3 ) δ =(+)70.514, (+)103.912, (+)111.241,(+)121.057, (+)122.735, (+)124.191, (+)126.727, (-)127.969,(+)128.220, (+)128.477, (-)140.237, (-)155.010; (-)158.484;GC-MS = M + 224 (100%), M + -OH 207.IR (CHCl 3 ): ν cm-1= 3390,1640,1600.M.P. = 53-54 °C.(S)-(+)-Phenyl-2benzo[b]furanyl carbinol (S)-(+)-27g:Synthetic method 7.30:[α] 20 D +16.94, (c 1.18 CHCl 3 )97.53% ee (Chiracel OD n-hexane/isopropanol) (S)-(+)-2a rt=10.00 min., (R)-(-)-2art=11.62 min.Physical and spectral data were identical to those described above forthe racemate (±)-27g.(±)-4'-Cyanophenyl-2-benzo[b]furanyl carbinol (±)-27h:Synthetic procedure 7.3.1.1H-NMR (200 MHz, CDCl 3 ) δ = 7.69-7.59 (m 4H), 7.54-7.41 (m2H), 7.28-7.18 (m 2H), 6.55 (s 1H), 6.00 (d 1H, 4.3 Hz), 2.71 (d 1H,4.3 Hz).IR (CHCl 3 ): ν cm-1= 3385,1620,1590.GC-MS = M + 249 (73%), M + -OH 232 (100%).M.P. = 115-116 °C
Chapter 8 184(±)-2',4'-Dichlorophenyl-2-benzo[b]furanyl carbinol (±)-27i:Synthetic procedure 7.3.1.1H-NMR (200 MHz, CDCl 3 ) δ = 7.64 (d 1H,8.6 Hz), 7.51-7.16 (m5H), 6.46 (s 1H), 6.28 (d 1H, 3.16 Hz), 2.76 (d 1H, 3.16 Hz).IR (CHCl 3 ): ν cm-1= 3380,1630,1590.GC-MS = M + 293 (87%), M + -OH 276 (100%).M.P. = 85-86 °C.(+)-2',4'-Dichlorophenyl-2-benzo[b]furanyl carbinol (+)-27i:Synthetic procedure 7.5.1[α] 20 D +38.5(c 2.98, CHCl 3 ).e.e. = 66 % HPLC: Chiracel OD n-hexane/propanole 99-1; 1 ml/min.rt= 61.52 min (+)-27i; 53.46 min (-)-27i1H-NMR (200 MHz, CDCl 3 ) of the crude of (+)-27i camphanicester (significant signals) δ= 6.62 (s) (+)-27i, 6.58 (s) (-)-27irelative ratio 7.99 / 1.72; e.e. 66%.Unknown absolute stereochemistry.Physical and spectral data were identical to those described above forthe racemate (±)-27i.(±)-4'-Fluorophenyl-2benzo[b]furanyl carbinol (±)-27 l:Synthetic procedure 7.3.1. or 7.301H NMR (200 MHz, CDCl 3 ) δ = 3.97 (s,1H), 5.85 (s,1H), 6.48(s,1H), 7.05 (t,10 Hz,2H), 7.55-7.21 (m, 6H).13C NMR (CDCl 3 ) δ= 69.764, 103.937, 111.206, 115.070, 115.499,121.101, 122.833, 124.331, 127.847, 128.453 d, 136.003 d, 154.975,158.177, 160.042, 164.942.13C J MOD NMR (CDCl 3 ) δ= (+)69.764, (+)103.937, (+)111.206,(+)115.070, (+)115.499, (+)121.101, (+)122.833, (+)124.331, (-)127.847, (-)128.453 d, (-)136.003 d, (-)154.975, (-)158.177, (-)160.042, (-)164.942.IR (CHCl 3 ): ν cm-1= 3370,1660,1600.GC-MS M + 242(100%), M + -OH 225 (86%).M.P.=58-59°C(R)-(-)-4'-Fluorophenyl-2benzo[b]furanyl carbinol (R)-(-)-27 l:Synthetic method 7.31.
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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
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 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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