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

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Chapter 8 179Argon was bubbled thrugh a solution of tetramethylguanidine (TMG,2263.3 µl, 2.1 mmol) in 2.0 ml of DMF for 15 min at 40°C before theaddition of 2-acetyliodophenol (500 mg, 1.91 mmol), bistriphenylphosphinepalladium (II) dichloride ( 66.7 mg, 0.09 mmol), CuI(18.1 mg, 0.09 mmol) and 1-Phenyl-2-propyn-1-ol 58a ( 1260.1 µl, 2.1mmol). The mixture was stirred under argon at 40°C for 4 h, wherebycolor changed from pale yellow to red/brown. After cooling, the reactionmixture was diluted with ethyl acetate. The organic layer was washed withwater and saturated NaCl solution and was finally dried over anhydrousNa 2 SO 4 . After evaporation of the solvent the resulting crude oil waspurified by flash chromatography on silica gel to afford (±)-71 in 78.9%chemical yield.8.37 Analytical data:4-Phenylbenzophenone 25a:Synthetic procedure 7.1.11H-NMR (300 MHz; CDCl 3 ) δ = 7.70-7.31 (m,14H)IR (CHCl 3 ): ν (cm-1) = 3030, 1690, 1610, 1290.GC-MS = 258 (M+ 70%).M.P. =110-112°C.4'-Phenyl-2-bromobenzophenone 25c:Synthetic procedure 7.1.11H-NMR (300 MHz; CDCl 3 ) δ = 7.88 (d 2H,8.7 Hz), 7.70-7.59 (m5H), 7.52-7.31 (m 6H).IR (CHCl 3 ): ν (cm-1 ) = 1675, 1625, 1300.GC-MS = 338 (M+ 72%), 181 (100%).M.P. = 97-98 °C.4'-Phenyl-2-fluorobenzophenone 25d:Synthetic procedure 7.1.11H-NMR (300 MHz; CDCl 3 ) δ = 7.95 (d 2H,8.5 Hz), 7.75-7.35(m8H), 7.30-7.10 (m 3H).13C-NMR (CDCl 3 ) δ = 192.92, 162.51, 157.50, 146.12, 139.83,136.04, 133.03, 132.87, 130.70, 130.65, 130.40, 128.93, 127.29,127.11, 127.01, 124.32, 124.25, 116.46, 116.03.
Chapter 8 180IR (CHCl 3 ): ν (cm-1 ) = 1680, 1600, 1295.GC-MS = 278 (M+ 100%).M.P. = 101-102 °C.4'-Phenyl-4-nitrobenzophenone 25e:Synthetic procedure 7.1.11H-NMR (300 MHz; CDCl 3 ) δ = 8.35 (d 2H,8.9Hz), 8.10-7.85 (m3H), 7.80-7.55 (m 4H), 7.50-7.30 (m 3H).IR (CHCl 3 ): ν (cm-1 )= 1660.GC-MS = 304 (M+ 100%).M.P. = 135-136 °C.4'-Phenyl-3-nitrobenzophenone 25f:Synthetic procedure 7.1.11H-NMR (300 MHz; CDCl 3 ) δ = 8.65 (s 1H), 8.46 (d 1H, 7.70 Hz),8.18 (d 1H, 6.10 Hz), 7.81 (d 2H, 7.7 Hz), 7.73-7.62 (m 5H), 7.49-7.35 (m 3H).IR (CHCl 3 ): ν (cm-1= 1675.GC-MS = 304 (M+ 100%).M.P. = 154-155 °C.Phenyl-2-benzo[b]furanone 26a:Synthetic procedure 7.2.1.1H-NMR (300 MHz; CDCl 3 ) δ = 8.07-8.02 (m 1H), 7.75-7.46 (m8H), 7.46-7.25 (m 1H).IR (CHCl 3 ): ν (cm-1= 1675,1605,1550.GC-MS = 222 M + (100%).M.P.= 105-106 °C.4'-Cyanophenyl-2-benzo[b]furanone 26b:Synthetic procedure 7.2.1.1H-NMR (300 MHz; CDCl 3 ) δ =8.16 (d 2H, 9.0Hz), 7.84 (d2H, 9.0Hz), 7.71 (d 1H,7.8Hz), 7.62-7.41 (m3H), 7.30 (d 1H 7.8Hz).IR (CHCl 3 ): ν cm-1= 2220,1680,1610,1550.GC-MS = 247 M + (100%).M.P.= 205-206 °C.2',4'-Dichlorophenyl-2-benzo[b]furanone 26c:Synthetic procedure 7.2.1.1H-NMR (300 MHz; CDCl 3 ) δ = 7.70 (d1H, 8.1 Hz), 7.59-7.51(m3H), 7.47 (s1H), 7.40 (m 3H).
Page 1 and 2:
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
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 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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