Advertisement

Opioids pp 241-277 | Cite as

Chemistry of Nonpeptide Opioids

  • S. Archer
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 104 / 1)

Abstract

During the past three decades interest in nonpeptide opioids has been rekindled in part by the introduction of a clinically acceptable analgesic of the mixed agoinst-antagonist type with reduced addiction liability (Archer et al. 1962), which was followed by the seminal papers by Martin (Martin 1967; Martin et al. 1976) on multiple opioid receptors. The next several years were marked by the development of more analgesics of the mixed agonist-antagonist class, pure narcotic antagonists devoid of agonist action, and the discovery of higher potent opioids in the oripavine, fentanyl, and meperidine series. On a parallel front the past few decades were marked by the introduction of a methadone maintenance program for narcotic addicts (Dole and Nyswander 1965); and the realization that heroin abusers are particularly susceptible to AIDS has stimulated research on new modalities for treating opiate addicts.

Keywords

Total Synthesis Lithium Aluminum Hydride Narcotic Antagonist Methyl Propiolate Propionic Anhydride 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aceto MD, Bowman ER, May EL, Harris LS, Woods JH, Smith CB, Medzihradsky F, Jacobson AE (1989) Very long-acting narcotic antagonists: the 14β-p-substituted cinnamoylaminomorphinones and their partial mu agonist codeinone relatives. Arzneimittelforschung 39: 570–575PubMedGoogle Scholar
  2. Ager JH, May EL (1960) Structures related to morphine: XIII. 2-Alkyl-2’-hydroxy- 5,9-dimethyl-6,7-benzomorphans and a more direct synthesis of the 2-phenethyl compound. J Org Chem 25: 984–986Google Scholar
  3. Albertson NF, Wetterau WF (1970) The synthesis of pentazocine. J Med Chem 13: 302–303PubMedGoogle Scholar
  4. Allen RM, Kirby GW (1970) Iodination of thebaine: a new route to 9-substituted indolinocodeinone derivatives. Chem Commun 1346Google Scholar
  5. Amann T, Zenk MH (1991) Formation of the morphine precursor salutaridine is catalyzed by a cytochrome P-450 enzyme in mammalian liver. Tetrahedron Lett 32: 3675–3678Google Scholar
  6. Archer S, Osei-Gyimah P (1979) Reaction of thebaine with dinitrogen tetroxide. J Heterocycl Chem 16: 389Google Scholar
  7. Archer S, Albertson NF, Harris LS, Pierson AK, Bird JG, Keats AS, Telford J, Papadopoulos CH (1962) Narcotic antagonists as analgesics. Science 137: 541–543PubMedGoogle Scholar
  8. Archer S, Albertson NF, Harris LS, Pierson AK, Bird JG (1964) Pentazocine. Strong analgesics and analgesic antagonists in the benzomorphan series. J Med Chem 7: 123–127PubMedGoogle Scholar
  9. Archer S, Seyed-Mozaffari A, Osei-Gyimah P, Bidlack JM, Abood LG (1983) 14β-(2-Bromoacetamido)morphine and 14β-(2-Bromoacetamido)-morphinone. J Med Chem 26:1775–1777PubMedGoogle Scholar
  10. Aridon AWD, Morrison AL (1950) Synthetic analgesics: VI. The synthesis of ketobemidone. J Chem Soc: 1469–1471Google Scholar
  11. Barltrop JA (1947) Synthesis in the morphine series: 1. Derivatives of bicyclo[3:3:1]-2-azanonane. J Chem Soc: 399–401Google Scholar
  12. Bentley KW (1954) The chemistry of the morphine alkaloids. Oxford University Press, LondonGoogle Scholar
  13. Bentley KW (1971) The morphine alkaloids. In: Manske RF (ed) The alkaloids, vol 13. Academic, New York, pp 75–120Google Scholar
  14. Bentley KW, Hardy DG (1963) New potent analgesics in the morphine series. Proc Chem Soc London, p 220Google Scholar
  15. Bergel F, Morrison AL (1948) Synthetic analgesics. Quart Revs (Lond) 2: 349–382Google Scholar
  16. Beyerman HC, Lie TS, Maat T, Bosman HH, Buurman E, Bijsterveld EJM, Sinnige HJM (1976) A convenient synthesis of codeine and morphine. Rec Trav Chim Pay Bas 95: 24–25Google Scholar
  17. Bidlack JM, Frey DK, Seyed-Mozaffari A, Archer S (1989) 14β-(Bromoacetamido) morphine irreversibly labels μ opioid receptors in rat brain membranes. Biochemistry 28:4333–4339PubMedGoogle Scholar
  18. Bidlack JM, Frey DK, Kaplan RA, Seyed-Mozaffari A, Archer S (1990) Affinity labeling of μ opioid receptors by sulfhydryl alkylating derivatives of morphine and morphinone. Mol Pharmacol 37: 50–59PubMedGoogle Scholar
  19. Billings RE, Booher R, Smits S, Pohland A, McMahon RE (1973) Metabolism of acetylmethadol. A sensitive assay for noracetylmethadol and the identification of a new active metabolite. J Med Chem 16: 305–306Google Scholar
  20. Billings RE, McMahon RE, Blake DA (1974) I-Acetylmethadol (LAM) treatment of opiate dependence. Plasma and urine levels of two pharmacologically active metabolites. Life Sci 14: 1437–1446Google Scholar
  21. Blane GF, Boura ALA, Fitzgerald AE, Lister RE (1967) Actions of etorphine hydrochloride (M99): a potent morphine-like agent. Br J Pharmacol Chem 30: 11–22Google Scholar
  22. Blumberg H, Pachter IJ, Metossian Z (1967) 14β-Hydroxydihydromorphinones. US Patent 3 332 950, 25 July; Chem Abstr (1967) 67:P100301aGoogle Scholar
  23. Booher RN, Pohland A (1975) Synthesis of a new metabolite of acetylmethadol. J Med Chem 18: 266–268PubMedGoogle Scholar
  24. Burke JR Jr, Bajwa BS, Jacobson AE, Rice KC, Streaty RA, Klee WR (1984) Probes for narcotic receptor mediated phenomena: 7. Synthesis and pharmacological properties of irreversible ligands specific for μ and δ opiate receptors. J Med Chem 27: 1570–1574Google Scholar
  25. Burke TR Jr, Jacobson AE, Rice KC, Silverton JV, Simonds WF, Streaty RA, Klee W (1986) Probes for narcotic receptor mediated phenomena. 12. cis-(+)-3- methylfentanyl isothiocyanate, a potent site-directed acylating agent for δ opioid receptors. Synthesis, absolute configuration and receptor enantioselectivity. J Med Chem 29: 1087–1093Google Scholar
  26. Carabateas PM, Grumbach L (1962) Strong analgesics. Some 1-substituted 4-phenyl-4-propioxypiperidines. J Med Chem 5: 913–919Google Scholar
  27. Casy AF, Parfitt RT (1986) Opioid analgesics. Plenum, New YorkGoogle Scholar
  28. Clark CR, Halfpenny PR, Hill RG, Horwell DC, Hughes J, Jarvis JC, Rees DC, Hofield DS (1988) Highly selective к opioid analgesics. Synthesis and structure- activity relationships of novel N-(1-aminocyclohexyl)aryl]acetamide and N-[aminocyclohexy)aryloxy]-acetamido derivatives. J Med Chem 31: 831–836PubMedGoogle Scholar
  29. Corrodi H, Hellerbach J, Zuest A, Hardegger E, Schnider O (1958) Hydroxymorphinans: XII. Configuration of morphinan. Helv Chim Acta 42: 212–217Google Scholar
  30. Costello GF, Main BG, Barlow JJ, Carroll JA, Shaw JS (1988) A novel series of potent and selective agonists at the opioid K-receptor. Eur J Pharmacol 151: 475–478PubMedGoogle Scholar
  31. deCosta BR, Bowen WD, Hellewell SB, George C, Rothman RB, Reid AA, Walker JM, Jacobson AE, Rice KC (1989) Alterations in the stereochemistry of the к-selective opioid agonist U50,488 result in high-affinity σ ligands. J Med Chem 32: 1996–2002Google Scholar
  32. deCosta BR, Rice KC, Bowen WD, Thurkauf A, Rothman RB, Band L, Jacobson AE, Radesca L, Conteras PC, Gray NM, Daly I, Iyengar S, Finn DT, Vazirini S, Walker JM (1990a) Synthesis and evaluation of N-substituted cis-N-methyl- 2-(1-pyrrolidinyl)cyclohexylamines as high affinity σ receptor ligands. Identification of a new class of highly potent and selective σ receptor probes. J Med Chem 32: 3100–3108Google Scholar
  33. deCosta BR, Rothman RB, Bykov RB, Bykov V, Band L, Pert A, Jacobson AE, Rice KC (1990b) Probes for narcotic receptor mediated phenomena: 17. Synthesis and evaluation of a series of trans-3,4-dichloro-N-methyl-N -[2-(1-pyrrolidinyl)cyclohexyl]benzamide (U50,488) related isothiocyanate derivatives as opioid receptor affinity ligands. J Med Chem 33: 1171–1176Google Scholar
  34. DeGraw JI, Christiansen JC, Brown VH, Cory MJ (1974) Grewe codeine method. Attempts to achieve a practical synthesis. J Heterocycl Chem 11: 363–367Google Scholar
  35. Dole VP, Nyswander M (1965) A medical treatment for diacetylmorphine (heroin) addiction: a clinical trial with methadone hydrochloride. JAMA 193: 640–650Google Scholar
  36. Donnerer J, Oka K, Brossi A, Rice KC, Spector S (1986) Presence and formation of codeine and morphine in the rat. Proc Natl Acad Sci USA 83: 4566–4567PubMedGoogle Scholar
  37. Eddy NB, May EL, Mosettig E (1952) Chemistry and pharmacology of the methadols and acetylmethadols. J Org Chem 17: 321–326Google Scholar
  38. Eisleb O (1941) New syntheses using sodamide. Chem Ber 74: 1433–1450Google Scholar
  39. Eisleb O (1945) Office of the Publication Board, Department of Commerce Report No. PB-981, 9611Google Scholar
  40. Elad D, Ginsburg D (1954) Synthesis in the morphine series: VI. The synthesis of morphine. J Chem Soc:3052–3056Google Scholar
  41. Evans DA, Mitch CH (1982) Studies directed toward the total synthesis of morphine alkaloids. Tetrahedron Lett 23: 285–289Google Scholar
  42. Gates M, Montzka TA (1964) Some potent morphine antagonists possessing high analgesic activity. J Med Chem 7: 127–131PubMedGoogle Scholar
  43. Gates M, Sheppard MS (1962) The closure of the oxide bridge in the morphine series. J Am Chem Soc 84: 4125–4130Google Scholar
  44. Gates M, Tschudi G (1956) The synthesis of morphine. J Am Chem Soc 78: 1380–1393Google Scholar
  45. Gordon M, Lafferty JJ, Tedeschi DA, Eddy NB, May EL (1961) A new potent analgesic antagonist. Nature 92: 1089Google Scholar
  46. Gritz ER, Shiffman SM, Jarvik ME, Schlesinger J, Charu V, Astra VC (1976) Naltrexone: physiological and psychological effects of single doses. Clin Pharmacol Ther 19: 773–776PubMedGoogle Scholar
  47. Grewe R, Friedrichson W (1967) Cyclization of octahydroisoquinoline derivatives by morphinan ring closure. Synthesis of dihydrothebainone. Chem Ber 100: 1550–1558Google Scholar
  48. Grewe R, Mondon A (1948) Synthesis in the phenanthrene Series: VI. Synthesis of morphinan. Chem Ber 81: 279–286Google Scholar
  49. Halfpenny PR, Hill RG, Horwell DC, Hughes J, Hunter DC, Johnson S, Rees DC (1989) Highly selective K opioid analgesics: 2. Synthesis and structure-activity relationships of novel N-[(2-aminocyclohexyl)aryl]acetamide derivatives. J Med Chem 32: 1620–1626PubMedGoogle Scholar
  50. Hayakawa K, Motohiro S, Fujii I, Kanematsu K (1981) Novel addition reaction of thebaine with acetylenic dienophiles: construction of a new morphine skeleton. J Am Chem Soc 103: 4605–4606Google Scholar
  51. Hollander CWD (1958) Racemization. US Patent 2819272, 7 Jan; Chem Abstr (1958) 52: 9223iGoogle Scholar
  52. Hollander CWD (1959) Racemization catalysts. US Patent 2 915 479, 1 Dec; Chem Abstr (1960) 54: 12165dGoogle Scholar
  53. Jaffe JH, Martin WR (1990) Opioid analgesics and antagonists. In: Gilman AG, Rail TW, Nies AS, Taylor P (eds) Goodman and Gilman’s the pharmacological basis of therapeutics, 8th edn. Pergamon, New York, p 512Google Scholar
  54. Janssen PAJ, Eddy NB (1960) Compounds related to pethidine: IV. New general chemical methods of increasing the analgesic activity of pethidine. J Med Chem 2: 31–45Google Scholar
  55. Janssen PAJ, Niemegeers CJE, Dony JGH (1963) The inhibitory effect of fentanyl and other morphine-like analgesics on the warm water induced tail withdrawal reflex in the rat. Arzneimittelforschung 13: 502–507Google Scholar
  56. Jasinski DR, Martin WR, Haerzten CA (1967) The human pharmacology and abuse potential of N-allylnoroxymorphone ( Naloxone ). J Pharmacol Exp Ther 157: 420–426Google Scholar
  57. Jasinski DR, Pevnick JS, Griffith JD (1978) Human pharmacology and abuse potential of the analgesic buprenorphine. A potential agent for treating narcotic addiction. Arch Gen Psychiatry 35: 501–516Google Scholar
  58. Kaplan LJ (1984) Analgesic 1-oxa-, aza and thia-spirocyclic compounds. US Patent 4438130; Chem Abstr (1984) 101: 54192wGoogle Scholar
  59. Karle IL, Gilardi RD, Fratini AV, Karle J (1969) Crystal structures of DL-cyclazocine and L-cyclazocine, and the absolute configuration of L-cyclazocine HBr H2O. Acta Crystallogr Sect B 25: 1469–1479Google Scholar
  60. Kirby GW, McLean D (1985) An efficient synthesis of 14β-aminocodeinone from thebaine. J Chem Soc Perkin Trans 1: 1443–1445Google Scholar
  61. Kitamura M, Hsiao Y, Noyori R, Takaya H (1988) General asymmetric synthesis of benzomorphans and morphinans via enantioselective hydrogenation. Tetrahedron Lett 28: 4829–4832Google Scholar
  62. Klee WA, Simonds WF, Sweat FW, Burke TR Jr, Jacobson AE, Rice KC (1982) Identification of a Mr 58000 glycoprotein subunit of the opiate receptor. FEBS Lett 150: 125–128PubMedGoogle Scholar
  63. Kobylecki RJ, Guest IG, Lewis JW, Kirby GW (1978a) Morphine derivatives. Ger Offen 2812580, 5 Oct; Chem Abstr (1979) 90: 87709tGoogle Scholar
  64. Kobylecki RJ, Guest IG, Lewis JW, Kirby GW (1978b) Morphine derivatives. Ger Offen 2 812 581; Chem Abstr (1979) 90: 39099r.Google Scholar
  65. Kobylecki RJ, Carling RW, Lord J AH, Smith CFC, Lane AC (1982) Common anionic receptor site hypothesis: its relevance to the antagonist action of naloxone. J Med Chem 25: 116–120PubMedGoogle Scholar
  66. Lahti RA, Mickelson MM, McCall JM, Von Voightlander PF (1985) [3H] U-69593 a highly selective Ligand for the opioid K receptor. Eur J Pharmacol 109:281–284PubMedGoogle Scholar
  67. Lednicer D (1982) Medicinal chemistry of central analgesics. In: Lednicer D (ed) Central analgesics. Wiley, New York, p 137Google Scholar
  68. Leimgruber W, Mohacsi E, Baruth H, Randall LO (1973) Levallorphan and related compounds. In: Braude MC, Harris LS, May EL, Smith JP, Villareal JE (eds) Narcotic antagonists. Raven, New York, pp 45–50Google Scholar
  69. Lenz GR, Evans SM, Walters DE, Hopfinger AJ (1987) Opiates. Academic, OrlandoGoogle Scholar
  70. Lewenstein MJ, Fishman J (1966) 14-Hydroxymorphine and codeine carboxymethyl oximes. US Patent 3320262, 16 May; Chem Abstr (1967) 67: 90989gGoogle Scholar
  71. Lewis J, Smith C, McCarthy P, Walter D, Kobylecki R, Myers M, Haynes A, Lewis C, Waltham K (1988) New 14-aminomorphinones and codeinones. problems of drug dependence. Natl Inst Drug Abuse Res Monogr Ser 90: 136–143Google Scholar
  72. Loew GH, Berkowitz DS (1978) Quantum chemical studies of N-substituent variation in the oxymorphone series of opiate narcotics. J Med Chem 21: 101–106PubMedGoogle Scholar
  73. Magnan J, Paterson SJ, Tavani A, Kosterlitz HW (1982) The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties. Naunyn Schmiedebergs Arch Pharmacol 319: 197–205PubMedGoogle Scholar
  74. Martin WR (1967) Opioid antagonists. Pharmacol Rev 19: 463–521PubMedGoogle Scholar
  75. Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE (1976) The effects of morphine- and nalorphine-like drugs in the nondependent and morphine- dependent chronic spinal dog. J Pharmacol Exp Ther 197: 517–532PubMedGoogle Scholar
  76. May EL, Ager JH (1959) Structures related to morphine: XI. Analogs and a diastereoisomer of 2’-hydroxy-2,5,9-trimethyl-6,7-benzomorphan. J Org Chem 24: 1432–1435Google Scholar
  77. May EL, Fry EM (1957) Structures related to morphine: VIII. Further synthesis in the benzomorphan series. J Org Chem 22: 1366–1369Google Scholar
  78. May EL, Kugita H (1961) Structures related to morphine: XV. Stereochemical control of methyl-metallo additions to 9-oxobenzo-morphans. J Org Chem 26: 158–163Google Scholar
  79. May EL, Kugita H, Ager JH (1961) Structures related to morphine: XVII. Further stereochemical studies with 9-oxobenzomorphans. J Org Chem 26: 1621–1624Google Scholar
  80. McMurry JE, Farina V, Scott WJ, Davidson AH, Summers DR, Shenyi A (1984) A new approach to morphinans: total synthesis of O-methylpallidinine. J Org Chem 49: 3803–3812Google Scholar
  81. Merz H, Langbein A, Stockhaus K, Walther G, Wick H (1973) Structure activity relationships in narcotic antagonists with N-furylmethyl substituents. In: Braude MC, Harris LS, May EL, Smith JP, Villareal JE (eds) Narcotic antagonists. Raven, New York, pp 91–108Google Scholar
  82. Merz H, Stockhaus K, Wick H (1975) Stereoisomeric 5,9-dimethyl-2’-hydroxy-2- tetrahydrofuryl-6,7-benzomorphans. Strong analgesics with non-morphine-like action profiles. J Med Chem 18: 996–1000Google Scholar
  83. Meyers Al, Bailey TR (1986) An asymetric synthesis of (+) morphinans in high enantiomeric purity. J Org Chem 51: 872–876Google Scholar
  84. Michne WF (1976) A 2,6-Methano-3-benzazocine related to the Thebaine Diels- Alder adduct derivatives. J Org Chem 41: 894–896Google Scholar
  85. Michne WF (1978) 2,6-methano-3-benzazocine-ll-propanols. Lack of antagonism between optical antipodes and observation of potent narcotic antagonism by two N-methyl derivatives. J Org Chem 21:1322–1324Google Scholar
  86. Michne WF, Albertson NF (1972) Analgesic l-oxidized-2,6-methano-3-benzazocines. J Med Chem 15: 1278–1281PubMedGoogle Scholar
  87. Michne WF, Salsbury RL, Michalec SJ (1977) Synthesis and narcotic agonist- antagonist evaluation of some 2,6-methano-3-benzazocine-ll-propanols. Analogues of the ring C bridged oripavine-7-methanols. J Med Chem 20: 682–686PubMedGoogle Scholar
  88. Michne WF, Lewis TR, Michalec SJ, Pierson AK, Rosenberg FJ (1979) (2,6- Methano-3-benzazocin-11β-yl)alkanones: 1. Alkylalkanones: a new series of N- methyl derivatives with novel opiate activity profiles. J Med Chem 22:1158–1163PubMedGoogle Scholar
  89. Monkovic I, Conway TT, Wong H, Perron YG, Pachter IJ, Belleau B (1973) Total synthesis and pharmacological activities of N-substituted 3,14-dihydroxymorphinans I. J Am Chem Soc 95: 7910–7912PubMedGoogle Scholar
  90. Monkovic I, Wong H, Pircio AW, Perron YG, Pachter IJ, Belleau B (1975) Oxilorphan and butorphanol. Potent narcotic antagonists and non-addicting analgesics in the 3,14-dihydroxymorphinan series V. Can J Chem 53: 3094–3102Google Scholar
  91. Moos WH, Gless RD, Rapoport H (1983) Codeine analogs. Synthesis of 4a-aryldecahydroisoquinolines containing nitrogen ring functionality and of octahydro-1H-indeno[l,2,3-ef]isoquinolines. A total synthesis of codeine. J Org Chem 48: 227–238Google Scholar
  92. Niemegeers CJE, Schellekens KHF, Van Bever WFM, Janssen PAJ (1976) Sufentanil, a very potent and extremely safe intravenous morphine-like compound in mice, rats and dogs. Arzneimittelforschung 26: 1551–1556PubMedGoogle Scholar
  93. Noyori R, Takaya H (1990) BINAP: an efficient chiral element for asymmetric catalysis. Acc Chem Res 23: 345–350Google Scholar
  94. Osei-Gyimah P, Archer S (1980) Synthesis and analgesic activity of some 14β-substituted analogues of morphine. J Med Chem 23: 162–166PubMedGoogle Scholar
  95. Osei-Gyimah P, Archer S, Gillan MGC, Kosterlitz HW (1981) Some 14β-substituted analogues of N-(cyclopropylmethy)normorphine. J Med Chem 24: 212–214PubMedGoogle Scholar
  96. Pachter IJ, Matossian Z (1968) 14-Hydroxydihydromorphinone. British Patent 1 119 270, 10 July; Chem Abstr (1968) 69: 87282q.Google Scholar
  97. Pfeiffer A, Brante V, Herz A, Emreich HM (1986) Psychotomimesis mediated by к opiate receptors. Science 233: 774–776PubMedGoogle Scholar
  98. Rahtz D, Paschelke G, Shroeder E (1977) New N-2-hydroxyalkyl-6,7-benzomorphan derivatives. Synthesis and preliminary pharmacology. Eur J Chim Ther 12: 271–278Google Scholar
  99. Rance MJ, Kobylecki RJ, Lane AC, Holgate MJ, Barnard EA (1981) In: Advances in endogenous and exogenous opioids. Proceedings of the international narcotics research conference, Kyoto, Japan, p 408Google Scholar
  100. Rapoport H, Lavigne JB (1953) Stereochemical studies in the morphine series. The relative configurations at carbons thirteen and fourteen. J Am Chem Soc 75: 5320–5324.Google Scholar
  101. Rapoport H, Sheldrich PS (1963) Diels-Alder reaction with thebaine: thermal rearrangement of some adducts from acetylenic dienophiles. J Am Chem Soc 85: 1636–1642Google Scholar
  102. Rice KC (1977) A rapid high-yield conversion of codeine to morphine. J Med Chem 20: 164–165PubMedGoogle Scholar
  103. Rice KC (1985) The development of a practical total synthesis of natural and unnatural codeine, morphine and thebaine, In: Phillipson JD, Roberts MF, Zenk MH (eds) The chemistry and biology of isoquinoline alkaloids. Springer, Berlin Heidelberg New York, pp 191–203Google Scholar
  104. Rice K, Jacobson AE, Burke TR Jr, Bajwa BS, Streaty RA, Klee WA (1983) Irreversible ligands with high selectivity toward δ or μ opiate receptors. Science 220: 314–316PubMedGoogle Scholar
  105. Robinson R, Sugasawa S (1931) Synthetical experiments in the morphine group I. J Chem Soc:3163–3172 Schnider O, Hellerbach J (1950) Synthesis of morphinans II. Helv Chim Acta 33: 1437–1448Google Scholar
  106. Schultz AG, Lucci RD, Napier JJ, Kinoshita H, Ravichandran R, Shannon P, Yee YK (1985) Studies directed at a synthesis of the morphine alkaloids. A photochemical approach. J Org Chem 50: 217–231Google Scholar
  107. Schultz AG, Green NJ, Archer S, Tham FS (1991) Photochemistry of codeinone derivatives. Development of potential photoaffinity labelling techniques for opiate receptors. J Am Chem Soc 113: 6280–6281Google Scholar
  108. Schwartz MA, Mami IS (1975) A biogenetically patterned synthesis of morphine alkaloids. J Am Chem Soc 97: 1238–1240Google Scholar
  109. Simonds WF, Burke TR Jr, Rice KC, Jacobson AE, Klee W (1985) Purification of the opiate receptor of NG-108-15 neuroblastoma-glioma hybrid cells. Proc Natl Acad Sci USA 82: 4974–4978PubMedGoogle Scholar
  110. Singh A, Archer S, Hoogsteen K. Hirshfield J (1982) Thebaine and acetylenic dienophiles. J Org Chem 47: 752–754Google Scholar
  111. Singh A, Kulling RK, Seyed-Mozaffari A, Archer S (1986) Methyl-9,14-didehydro- 4,5-epoxy-3-methoxy-17-methyl-2-methylene-6-oxothebinan-P-acetate. J Org Chem 51: 3378–3380.Google Scholar
  112. Stork G (1952) Stereochemistry and reaction mechanisms of the morphine alkaloids. In: Manske RHF, Holmes HL (eds) The alkaloids, vol 2. Academic, New York, p 171Google Scholar
  113. Szantay C, Barbzai-Beke M, Pechy P, Blasko G, Dornyhei G (1982) Studies aimed at the synthesis of morphine: 3. Synthesis of (±)-salutaridine via phenolic oxidative coupling of (±)-reticuline. J Org Chem 47: 594–596Google Scholar
  114. Szmuszkovicz J, Von Voightlander PF (1982) Benzeneacetamide amines. Structurally novel non-mu opioids. J Med Chem 25: 1125–1126Google Scholar
  115. Theuns HG, Janssen RHAM, Biessels HWA, Menichini F, Salemin KCA (1984) A new rearrangement product of thebaine isolated from Papaver bracteatum Lindl. Structural assignment of thebaine N-oxides. J Chem Soc Perkin Trans I: 1701–1706Google Scholar
  116. Thorp RH, Walton E, Ofner P (1947) Optical isomers of amidone, with a note on isoamidone. Nature 160: 605–606PubMedGoogle Scholar
  117. Thurkauf A, deCosta B, Rice KC (1989) Synthesis of tritium labelled (-)-U 50 488. A selective kappa opioid agonist. J Labelled Compds Radiopharmaceut 27: 577–582Google Scholar
  118. Toth JE, Fuchs PL (1987) Total synthesis of (dl)-morphine. J Org Chem 52: 473–475Google Scholar
  119. Toth JE, Hamann PR, Fuchs PL (1988) Studies culminating in the total synthesis of (dl)-morphine. J Org Chem 53: 4694–4708Google Scholar
  120. Van Bever WFM, Niemegeers CJE, Janssen PAJ (1974) Synthetic analgesics. Synthesis and pharmacology of the diastereoisomers of N-[methyl-1-(2-phenyl)- 4-piperidyl]-N-phenylpropanamide and N-[3-methyl-1-(1-methyl-2-phenethyl]-4- piperidyl-N-phenylpropanamide. J Med Chem 17: 1047–1054PubMedGoogle Scholar
  121. Van Bever WFM, Niemegeers CFE, Schellekens KHF, Janssen PAJ (1976) N-4-Substituted 1-(2-arylethyl)-4-piperidinyl-N-phenylpropanamides, a novel series of extremely potent analgesics with unusually high safety margin. Arzneimittelforschung 26:1548–1551PubMedGoogle Scholar
  122. Van Daele GHP, DeBruyn MLF, Boev JM, Sanczuk S, Agten JTM, Janssen PAJ (1976) Synthetic analgesics: N-(1-[2-arylethyl]-4-substituted 4-piperidinyl)-N-arylalkanamides. Arzneimittelforschung 26: 1521–1531PubMedGoogle Scholar
  123. Von Voightlander PF, Lahti Ra, Ludens JH (1983) U-50488. A selective and structurally novel non-mu (Kappa) opioid agonist. J Pharmacol Exp Ther 224: 7–12Google Scholar
  124. Weijlard J, Orohovats PD, Sullivan AP Jr, Purdue G, Heath FK, Pfister KIII (1956) A new synthetic analgesic. J Am Chem Soc 78: 2342–2343Google Scholar
  125. Weiss U (1955) Derivatives of morphine: I. 14-hydroxydihydromorphinone. J Am Chem Soc 77: 5891–5892Google Scholar
  126. Weitz CJ, Faull KF, Goldstein A (1987) Synthesis of the skeleton of the morphine molecule by mammalian liver. Nature 330: 674–677PubMedGoogle Scholar
  127. Weller DD, Rapoport H (1976) A practical synthesis of codeine from dihydrothebainone. J Med Chem 19: 1171–1175PubMedGoogle Scholar
  128. Barber RB, Rapoport H, (1976) Conversion of thebaine to codeine. J Med Chem 19: 1175–1180PubMedGoogle Scholar
  129. Weller DD, Stirchak EP, Weller DL (1983) Synthesis of 3-methyl-5,6-dihydro-3H-benzofuro[3,2-e]isoquinolin-7(7aH)-ones. J Org Chem 48: 4597–4605.Google Scholar
  130. Ziering A, Lee J (1947) Piperidine derivatives: V. l,3-Dialkyl-4-aryl-4-accyloxypiperidines. J Org Chem 12: 911–914PubMedGoogle Scholar
  131. Ziering A, Malatestinic N, Williams T, Brossi A (1970) 3’-Methyl, 8-methyl, and 8-phenyl derivatives of 5,9-dimethyl-6,7-benzomorphans. J Med Chem 13:9–13PubMedGoogle Scholar
  132. Zimmerman DM, Nickander R, Horng JS, Wong DT (1975) New structural concepts for narcotic antagonists defined in a 4-phenylpiperidine series. Nature 275: 332–334Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • S. Archer

There are no affiliations available

Personalised recommendations