Chapter 9 21531) De Felice, R.; Johnson, D. G. <strong>and</strong> Galgiani, J. N. AntimicrobAgents Chemo<strong>the</strong>r 1981,19, 1073-1074.32) Kraemer, F. B.; Pont, A. Am. J. Med. 1986, 80, 616-622.33) Miett<strong>in</strong>en, J. A. J. Lipid Res. 1988, 29, 43-51; Gyll<strong>in</strong>g, H.;Vanhanen, H.; Miett<strong>in</strong>en, J. A. Metabolism, 1991, 49, 35-41 <strong>and</strong>references <strong>the</strong>re<strong>in</strong>.34) For a review, see: Van den Bossche, H.; Janssen, P. A. J. Targetsites <strong>of</strong> fungicide action; Koller, W., Ed.; Boca Raton, FL, 1992;pp. 227-254.35) Ballard, S. A.; Ladola, A.; Tarbit, M. H. A. Biochem. Pharmacol.1988, 37, 4643-4651.36) Rotste<strong>in</strong>, D. M.; Kertesz, D. J.; Walker, K. A. M.; Sw<strong>in</strong>ney, D. C.J. Med. Chem. 1992, 35, 2818-2825.37) Walker, K. A. M.; Kertesz, D. J.; Rotste<strong>in</strong>, D. M.; Sw<strong>in</strong>ney, D. C.J. Med. Chem. 1993, 36, 2235-2237.38) Camps, P.; Farres, X.; Garcia, M. L.; G<strong>in</strong>esta, J.; Pascual, J.;Mauleon, D.; Garganico, G. Tetrahedron : Asymmetry 1995, 6,1283-1294.39) Heeres, J.; Hendrickx, R. <strong>and</strong> Van Cutsem J. Med. Chem. 1983,26, 611-613.40) Camps, P.; Farres, X.; Garcia, M. L.; Mauleon, D.; Garganico, G.Tetrahedron : Asymmetry 1995, 6, 2365-2368.41) Sakesena, A. K.; Girijavallabham, V. M.; Lovey, R. G.; Pike, R.E.; Desai, J. A.; Hare, G. R. S.; Loendenberg, D.; Cacciapuoti, A.;Parmegiani, M. Biorg. Med. Chem. Lett. 1994, 4, 2023-2028.42) Van Cutsen, J.; Van gerven, F.; Zaman, R. <strong>and</strong> Janssen, P. A. J.Chemo<strong>the</strong>r. 1983, 29, 322-331.43) Godefroi, E. F.; Heeres, J.; Van Cutsem, E. <strong>and</strong> Janssen, P. A. J. J.Med. Chem. 1969, 12, 784-791.44) Yamaguchi, H.; Hiratani, T. <strong>and</strong> Plempel, M. Arzneim-Forsch1983, 33, 546-551.45) Schar, G.; Kayser, F. H. <strong>and</strong> Dupont, M. C. Chemoter. 1976, 22,211-220.46) Hell, R. C.; Brodger, R. N.; Parkers, G. E.; Sperght, T. M.; Avery,G. S. Drug 1980, 19, 7-30.47) Menuier, F.; Cruciani, M.; Klastersky, J. Eur. J. Cancer Cl<strong>in</strong>.Oncol. 1983; 19, 43-48.
Chapter 9 21648) Gip, L. <strong>and</strong> Forsstrom, S. Mykosen 1982, 27, 231-241.49) Heel, R.C.; Brodgen, R. N.; Speight, T. M. <strong>and</strong> Avery, G. S. Drugs1978, 16, 177-201.50) Yoshiharu, Y.; Kenzo, F.; Motoo, U.; Heizo, S. Nippon Saik<strong>in</strong>gakuZasshi 1979, 36, 813-825.51) Sud, I. J. <strong>and</strong> Fe<strong>in</strong>gold, D. S. J. Invest. Dermatol. 1981, 76, 438-441.52) Thienpont, D.; Van Cutsem, J. M.; Niemegeers, C. J. E. <strong>and</strong>Marsboom, R. Arzneim-Forsch 1975, 25, 224-230.53) Kessler, H. J. Arzneim-Forsch 1979, 29, 1344-1351.54) Jevons, S.; Gymer, G. E.; Brammer, K. W.; Cox, D. A. <strong>and</strong>Lemm<strong>in</strong>g, M. R. G. Antimicrob. Agents Chemo<strong>the</strong>r. 1979, 15, 597-602.55) International Antifungal Symposium: Bifonazole. ExcerptaMedica: Amsterdam 1982, 104-112.56) International Antifungal Symposium: Bifonazole. ExcerptaMedica: Amsterdam 1982, 2-17.57) International Antifungal Symposium: Bifonazole. ExcerptaMedica: Amsterdam 1982, 37-4058) International Antifungal Symposium: Bifonazole. ExcerptaMedica: Amsterdam 1982, 74-76, 88-94,104-112, 120-125, 126-128, 129-135.59) Massa, S.; Stefancich, G.; Corelli, F.; Silvestri, R.; Panico, S.;Artico, M.; Simonetti, N. Il farmaco 1988, 43, 639-704.60) Massa, S.; Di Santo, R.; Artico, M.; Costi, R.; Apuzzo, G.;Simonetti, G.; Artico, M. Med. Chem. Res. 1992, 148-153.61) Buchel, H. D.; Draber, W.; Regal, E. <strong>and</strong> Plempel, M. Drugs Made<strong>in</strong> Germany 1972, 15, 79-94.62) Rumler, W. <strong>and</strong> He<strong>in</strong>s, S. Mykosen 1983, 26, 293-2297.63) Yamaguchi, H. <strong>and</strong> Iwata, K. Sabouraudia 1979, 17, 311-322.64) Shadomy, S. Antimicrob. Agents Chemo<strong>the</strong>r. 1971, 169-174.65) Burgess, M. A. <strong>and</strong> Bodey, G. P. Antimicrob. Agents Chemo<strong>the</strong>r.1972,2, 423-426.66) Wright, J. C. J. Natl. Med. Ass. 1985, 77, 617.67) Young, J. L.; Percy, C. L.; Asire, A. J. Incidence <strong>of</strong> mortality data(1973-77), N.I.H., Be<strong>the</strong>sda.N°81, 2330.
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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
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Chapter 7 157Finally an hypothesis
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Chapter 8 159were washed with a sat
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Chapter 8 16145 min, the mixture wa
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Chapter 8 1638.9 Decarboxylation of
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- Page 228 and 229: Chapter 9 213References chapter 1:1
- 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