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

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Chapter 8 201Physical and spectral data were identical to those described above forthe racemate (±)-58i.(±)-1-(2-Methylphenyl)-2-propyn-1-ol (±)-58 l:Synthetic method 7.23.41H-NMR (200 MHz, CDCl 3 ) δ =2.38 (d 1H, J=51 Hz) 2.49 (s 3H),2.68 (d 1H, J=2.1 Hz), 5.65 (dd 1H, J=2.1 Hz, J= 5.03 Hz), 7.24-7.22(m 1H), 7.31-7.27 (m 2 H), 7.72-7.70 (m 1H).13C NMR (CDCl 3 ) ν = 19.04, 62.39, 74.84, 83.52, 126.42, 126.57,128.72, 130.95, 136.07, 138.042.GC-MS= 145 M + (18%), 121 (100%).MP= 30.6-32.0.(R)-(-)-1-(2-Methylphenyl)-2-propyn-1-ol (R)-(-)-58 l:Synthetic method 7.28.2[α] 20 D -18.1 (c 0.65, CHCl 3 ). 80.4% ee .Physical and spectral data were identical to those described above forthe racemate (±)58 l.(±)-1-(2,4 Dichlorophenyl)-2-propyn-1-ol (±)-58 m:Synthetic method 7.23.41H-NMR (200 MHz, CDCl 3 ) δ =22.68 (d 1H, J=5.43 Hz), 2.71 (d 1H,J=2.04 Hz), 5.79 (dd 1H, J=5.43 Hz,J=2.04 Hz), 7.33 (d 1H, J=8.35Hz), 7.43 (s 1H), 7.73 (d 1H J=8.35 Hz).13C NMR (CDCl 3 ) δ = 61.29, 75.29, 82.18, 127.73, 129.31, 129.68,133.56, 135.18, 136.22.MP=oil.(±)-1-Phenyl-2-propyn-3-trimethylsilyl-1-ol (±)-59a:Synthetic method 7.23.21H-NMR (200 MHz, CDCl 3 ) δ = 0.00 (s 9H), 2.40 (s1H), 5.65 (s1H),7.67-7.23 (m5H).IR (CHCl 3 ) ν cm-1 = 3620, 3450,3020,2090.MP = oil.(±)-1-(4-Methylphenyl)-2-propyn-3-trimethylsilyl-1-ol(±)-59b:Synthetic method 7.23.21H-NMR (200 MHz, CDCl 3 ) δ = 0.00 (s 9H), 2.12 (s 1H), 2.34 (s 3H),5.39 (s 1H), 7.16 (d 2H, J =8.02 Hz), 7.41 (d 2H, J = 8.02 Hz).IR (CHCl 3 ) ν cm-1 = 3600, 3470,3020,2100.MP = oil
Chapter 8 202(±)-1-(4-Fluorophenyl)-2-propyn-3-trimethylsilyl-1-ol(±)-59c:Synthetic method 7.23.21H-NMR (200 MHz, CDCl 3 ) δ = 0.00 (s 9H), 2.16 (d 1H, J = 5.1 Hz),5.42 (d 1H, J = 5.1 Hz), 7.06 (t 2H, 9.1 Hz), 7.51 (dd 2H, J= 6.1 Hz,9.1 Hz).IR (CHCl 3 ) ν cm-1 = 3580, 3460,3010,2080.MP = oil(±)-1-(4-Chlorophenyl)-2-propyn-3-trimethylsilyl-1-ol(±)-59d:Synthetic method 7.23.21H-NMR (200 MHz, CDCl 3 ) δ = 0.00 (s 9H), 2.01 (s 1H), 5.40 (s1H). 7.30 (d 2H, J = 8.24 Hz), 7.46 (d 2H, J = 8.24 Hz).IR (CHCl 3 ) ν cm-1 = 3580, 3460,3010,2080.MP = oil(±)-1-(4-Cyanophenyl) – 2 – propyn – 3 – trimethylsilyl – 1 - ol (±)-59e:Synthetic method 7.23.21H-NMR (200 MHz, CDCl 3 ) δ = 0.00 (s 9H), 2.31 (s 1H), 5.50 (s1H), 7.66 (m 4H).IR (CHCl 3 ) ν cm-1 = 3544, 3425, 2960, 2232, 2173, 1608.MP = oil(±)-1-(4-Nitrophenyl)-2-propyn-3-trimethylsilyl-1-ol (±)-59f:Synthetic method 7.23.21H-NMR (200 MHz, CDCl 3 ) δ = 0.00 (s 9H), 2.27 (s 1H), 5.54 (s1H),7.71 (d 2H, J= 8.73 Hz), 8,22 (d 2H, J= 8.73 Hz).MP = oil.(±)-1-(3,4-Dimethoxyphenyl)-2-propyn-3-trimethylsilyl-1-ol (±)-59g:Synthetic method 7.23.21H-NMR (200 MHz, CDCl 3 ) δ = 0.00 (s 9H), 2.20 (d 1H, J = 4.42Hz), 3.92 (s 3H), 3.96 (s 3H), 5,44 (d 1H, J = 4.42 Hz), 6.90 (d 1H, J= 8.17 Hz) 7.11 (d 1H, J = 8.17 Hz), 7.15 (s 1H).13C NMR (CDCl 3 ) δ = 0.000, 55.98, 56.14, 91.67, 105.312, 110.29,111,22, 119,36, 133.25, 145.68, 149.37.MP= oil.
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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(±)-
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 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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