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

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Chapter 8 197IR (CHCl 3 ) ν cm-1 = 420,3020,1620, 1600;MP: Oil(±)-56b:Synthetic method 7.21.1 or 7.21.21H-NMR (200 MHz, CDCl 3 ) δ = 2.55 (s 2H), 5.22 (s 1H), 7.33-7.65(m13H).IR (CHCl 3 ) ν cm-1 = 3080,3020,1610, 1590;MP: Oil(±)-56c:Synthetic method 7.21.1 or 7.21.21H-NMR (200 MHz, CDCl 3 ) δ = 2.28 (s 2H), 5.21 (s1H), 6.45 (s1H),7.10-7.21 (m 3H), 7.27-7.47 (m 6H).IR (CHCl 3 ) ν cm-1 = 3420,3120,1620, 1600;MP: Oil.(±)-56d:Synthetic method 7.21.1 or 7.21.21H-NMR (200 MHz, CDCl 3 ) δ = 1.91 (s 2H), 5.69 (s 1H), 6.55 (s1H), 7.15-7.7.27 (m 3H), 7.39-7.52 (m 4H).IR (CHCl 3 ) ν cm-1 = 3390,3120,1620, 1600;MP: Oil.(+)-56d:Synthetic method 7.21.1 or 7.21.2[α] 20 D = not measurable 20%e.e. by chiral HPLC(Chiracel OD).Physical and spectral data were identical with those described abovefor the racemate (±)-56d.(±)-57a as mixture of diasteroisomers:Synthetic method 7.22.1H-NMR (300 MHz, CDCl 3 ) δ = 1.63 (d 3H J =6.7 Hz), 5.94 (m 1H),6.25 (s 1H), 7.06-7.28 (m 4H), 7.33-7.59 (m19H), 7.68-7.91 (m 4H).57b:Synthetic method 7.22.1H-NMR (300 MHz, CDCl 3 ) δ = 1.75 (d 3H J =7.0 Hz), 1.85 (d3H J=7.0 Hz), 6.05 (q J =7.0 Hz, dq J =6.17 Hz and J =8.8 Hz) 7.05-804m, 8.13 (d 1H, J =8.8 Hz), 11.95 (d 1H, J =7.0 Hz).FAB MS= 705 M+.HPLC: Lichrocart 250X4, Lichrospher n-hexane/EtAc gradient rt16.40 min
Chapter 8 19857c:Synthetic method 7.22.1H-NMR (300 MHz, CDCl 3 ) δ = 1.75 (d 3H J =7.0 Hz), 1.85 (d3H J=7.0 Hz), 6.05 (q J =7.0 Hz, dq J =6.17 Hz and J =8.8 Hz) 7.05-804m, 8.05 (d 1H, J =8.8 Hz), 11.88 (d 1H, J =7.0 Hz).FAB MS= 705 M+.HPLC: Lichrocart 250X4, Lichrospher n-hexane/EtAc gradient rt17.66 min(±)-57d mixture of diasteroisomers:Synthetic method 7.22.1H-NMR (200 MHz, CDCl 3 ) δ = 1.52 (d 3H J =7.10 Hz), 1.62 (d 3HJ =7.10 Hz), 5.13 (m 1H), 5.32 (m m1H), 7.03-7.58 (m 24H), 8.01(d 1H J=8.5 Hz) 8.27 (s 1H) 11.62 (m2H).FAB MS= 604 M+.(±)-1-Phenyl-2-propyn-1-ol (±)-58a:Synthetic methods 7.23.1, 7.23.3.1, 7.23.3.2, 7.23.4. The compoundis commercially available.1H-NMR (200 MHz, CDCl 3 ) δ = 2.28 (d 1H, 6.23 Hz), 2.69 (d 1H, J =2.17 Hz), 5.48 (dd 1H, J=2.17 Hz; J=6.21 Hz), 7.59-7.32 (m3H).13C NMR (CDCl 3 ) ν = 64.05, 74.65, 83.36, 126.43, 128.27, 128.42,139.81.IR (CHCl 3 ) ν cm-1 = 3510, 3320, 3080, 2840, 2120.MP =oil.(±)-1-(4-Methylphenyl)-2-propyn-1-ol (±)-58b:Synthetic method 7.23.3.1 or 7.23.4.1H-NMR (200 MHz, CDCl 3 ) δ = 2.19 (d 1H, J =4.12 Hz), 2.40(s 3H), 2.69 (d 1H, J = 2.2 Hz), 5.48 (d 1H, J = 4.12 Hz), 7.24 (d 2H,J= 8.12 Hz), 7.48 (d 2H, J= 8.12 Hz).13C NMR (CDCl 3 ) δ = 21.29, 64.49, 74.72, 83.85, 126.71, 129.51,137.42, 138.59.IR (CHCl 3 ) ν cm-1 = 3540, 3380, 3280, 2120, 1610, 1510.MP = oil.(R)-(-)-1-(4-Methylphenyl)-2-propyn-1-ol (R)-(-)-58b:Synthetic methods 7.28.1, 7.28.2[α] 20 D -27.9 (c 3.05, CHCl 3 ). 75.7% ee.Physical and spectral data were identical to those described above forthe racemate (±)58b.
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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
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 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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