Chemical Modification of the Tetracyclines

  • W. Rogalski
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 78)

Abstract

The tetracyclines are a group of broad-spectrum antibiotics which, even 30 years after their discovery, have retained a prominent position in the treatment of infectious diseases.

Keywords

Antibacterial Activity Minimum Inhibitory Concentration Total Synthesis Zwitterionic Form Tetracycline Antibiotic 
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References

  1. Andre T, Ullberg S (1957) Radioactive tetracycline. J Am Chem Soc 79:494–495Google Scholar
  2. Bakhtiar M, Selwyn S (1982) Comparative studies on the bactericidal activities of tetracyclines, chloramphenicol, and other “bacteriostatic” antibiotics. In: Periti P, Grassi GG (eds) Current chemotherapy and immunotherapy, proceedings of the 12th international congress of chemotherapy, vol. I. American Society for Microbiology, Washington, pp 76–77Google Scholar
  3. Bakhtiar M, Selwyn S (1983) Antibacterial activity of a new thiatetracycline. J Antimicrob Chemother 11:291PubMedGoogle Scholar
  4. Ball PR, Shales SW, Chopra I (1980) Plasmid-mediated tetracycline resistance in Escherichia coli involves increased efflux of the antibiotic. Biochem Biophys Res Commun 93:74–81PubMedGoogle Scholar
  5. Barrett GC (1963) Synthesis of tetracycline analogs. J Pharm Sci 52:309–330PubMedGoogle Scholar
  6. Beereboom JJ, Butler K (1962) Hydrolysis of 2-decarboxamido-2-cyano-6-deoxytetracycline derivatives. U.S. Patent 3,069, 467Google Scholar
  7. Beereboom JJ, Ursprung JJ, Rennhard HH, Stephens CR (1960) Further 6-deoxytetracycline studies: effect of aromatic substituents on biological activity. J Am Chem Soc 82:1003–1004Google Scholar
  8. Berlin YA, Kolosov MN, Vasina IV, Yartseva IV (1968) The structure of chromocyclomycin. Chem Commun 762–763Google Scholar
  9. Bernardelli C, Bucher G, Lauria F, Logemann W, Tosolini G, Vita G (1967) Über die Einhorn-Reaktion mit Aminosäuren. Liebigs Ann Chem 706:243–249Google Scholar
  10. Bernardi L, Castiglione R De, Colonna V, Masi P, Mazzoleni R (1974) Tetracycline derivatives. I - Esters of 5-oxytetracyclines: chemistry and biological activity. Farmaco (Sci) 29:902–909Google Scholar
  11. Bernardi L, Castiglione R De, Scarponi U (1975 a) Simple methylation of amides. Chem Commun 320–321Google Scholar
  12. Bernardi L, Castiglione R De, Colonna V, Masi P (1975 b) Tetracycline derivatives. Note II. A practical synthesis of minocycline. Farmaco (Sci) 30:736–741Google Scholar
  13. Bernardi L, Castiglione R De, Masi P, Mazzoleni R, Scarponi U (1975 c) Tetracycline derivatives. Note III. 7- and 9-methyltetracyclines: synthesis and biological activity. Farmaco [Sci] 30:1025–1030Google Scholar
  14. Bitha P, Hlavka JJ, Boothe JH (1970) 6-Fluorotetracyclines. J Med Chem 13:89–92PubMedGoogle Scholar
  15. Blackwood RK, English AR (1970) Structure-activity relationships in the tetracycline series. Adv Appl Microbiol 13:237–266Google Scholar
  16. Blackwood RK, Stephens CR (1964) Novel C-4 modified tetracycline derivatives. J Am Chem Soc 86:2736–2737Google Scholar
  17. Blackwood RK, Stephens CR (1965) Some transformations of tetracycline at the 4-position. Can J Chem 43:1382–1388Google Scholar
  18. Blackwood RK, Rennhard HH, Stephens CR (1960 a) Some transformations at the 12a-position of the tetracyclines. J Am Chem Soc 82:745–746Google Scholar
  19. Blackwood RK, Rennhard HH, Stephens CR (1960 b) Some transformations at the 12a-position in the tetracycline series. J Am Chem Soc 82:5194–5197Google Scholar
  20. Blackwood RK, Beereboom JJ, Rennhard HH, Schach von Wittenau M, Stephens CR (1961) 6-Methylenetetracyclines. A new class of tetracycline antibiotics. J Am Chem Soc 83:2773–2775Google Scholar
  21. Blackwood RK, Beereboom JJ, Rennhard HH, Schach von Wittenau M, Stephens CR (1963) 6-Methylenetetracyclines. J Am Chem Soc 85:3943–3953Google Scholar
  22. Boothe JH, Hlavka JJ (1978) Tetracyclines. Encycl Chem Tech 3:64–78Google Scholar
  23. Boothe JH, Bonvicino GE, Waller CW, Petisi JP, Wilkinson RW, Broschard RB (1958) Chemistry of the tetracycline antibiotics. J Am Chem Soc 80:1654–1657Google Scholar
  24. Boothe JH, Kende AS, Fields TL, Wilkinson RG (1959) Total synthesis of tetracyclines. I- (±)-Dedimethylamino-12a-deoxy-6-demethylanhydrochloro tetracycline. J Am Chem Soc 81:1006–1007Google Scholar
  25. Boothe JH, Hlavka JJ, Petisi JP, Spencer JL (1960) 6-Deoxytetracyclines. I. Chemical modification by electrophilic substitution. J Am Chem Soc 82:1253–1254Google Scholar
  26. Brown JR, Ireland DS (1978) Structural requirements for tetracycline activity. Pharmacol Chemother 15:161–202Google Scholar
  27. Brunzell A (1962) N-Pyrrolidinomethyltetracycline. Stabilität in Lösungen und papierchromatographische Prüfung. Acta Chem Scand 16:245–246Google Scholar
  28. Cammarata A, Yau SJ, Collett JH, Martin AN (1970) Correlation of the potencies of tetracyclines in vitro with a D-ring substituent Index. Mol Pharmacol 6:61–66PubMedGoogle Scholar
  29. Chandra R, Dabral PK, Sharma MC, Mukerji S (1980) Water soluble tetracycline derivative: Part-II: 2-(D-glucosaminomethyl) tetracycline dihydrochloride. Indian J Pharm Sci 42:33–36Google Scholar
  30. Cheney LC, Fayetteville, Risser WC, Gottstein WJ (1958) Mannich bases of tetracycline antibiotics. U.S. Patent 3,104, 240Google Scholar
  31. Chopra I, Howe TGB, Linton AH, Linton KB, Richmond MH, Speller DCE (1981) The tetracyclines: prospects at the beginning of the 1980s. J Antimicrob Chemother 8:5–21PubMedGoogle Scholar
  32. Chu DTW, Huckin SN (1980) Chemistry of hexamethyldisilazane. Silylation of ß-diketones and amination of ß-triketones. Can J Chem 58:138–142Google Scholar
  33. Chu DTW, Huckin SN, Bernstein E, Garmaise DL, Egan RS, Stanaszek RS (1981) Chemistry of chelocardin. V. Condensation with amino reagents. Can J Chem 59:763–767Google Scholar
  34. Church RFR, Schaub RE, Weiss MJ (1971) Synthesis of 7-dimethylamino-6-demethyl-6- deoxytetracycline (Minocycline) via 9-nitro-6-demethyl-6-deoxytetracycline. J Org Chem 36:723–725PubMedGoogle Scholar
  35. Cid-Dresdner H (1965) The crystal structure of terramycin hydrochloride, C22H24N2O9.HCl. Z Kristallogr 121:170–189Google Scholar
  36. Clive DLJ (1968) Chemistry of tetracyclines. Q Rev Chem Soc 22:435–456Google Scholar
  37. Colaizzi JL, Klink PR (1969) pH-partition behavior of tetracyclines. J Pharm Sci 58:1184–1189PubMedGoogle Scholar
  38. Collett JH, Collett C, Martin AN, Cammarata A (1970) The effects of some tetracyclines on synchronously growing cultures of Escherichia coli B/r. J Pharm Pharmacol 22:672–678PubMedGoogle Scholar
  39. Conover LH, Butler K, Johnston JD, Korst JJ, Woodward RB (1962) The total synthesis of 6-demethyl-6-deoxytetracycline. J Am Chem Soc 84:3222–3224Google Scholar
  40. de Carneri I, Coppi G, Lauria F, Logemann W (1961) Una nouva tetraciclina solubile: la tetraciclina-L-metilenlisina. Farmaco [Prat] 16:65–79Google Scholar
  41. Dingeldein E, Ungethüm W (1979) Pharmacokinetics of EMD 33 330, a totally synthetic tetracycline. 11th International congress of chemotherapy and 19th interscience conference on antimicrobial agents chemotherapy, Boston, Oct 1979, Abstract 510Google Scholar
  42. Dingeldein E, Wahlig H (1977) EMD 33 330, a new synthetic thiatetracycline. In vitro and in vivo evaluation. XVII. Interscience conference on antimicrobial agents and chemotherapy, New York, Oct 1977; Abstract 71Google Scholar
  43. Doerschuk AP, Bitler BA, McCormick JRD (1955) Reversible isomerizations in the tetracycline family. J Am Chem Soc 77:4687Google Scholar
  44. Donohue J, Dunitz JD, Trueblood KN, Webster MS (1963) The crystal structure of aureomycin (Chlortetracycline) hydrochloride. Configuration, bond distances and conformation. J Am Chem Soc 85:851–856Google Scholar
  45. Dürckheimer W (1975) Tetracycline: Chemie, Biochemie und Struktur-Wirkungs-Beziehungen. Angew Chem 87:751–764Google Scholar
  46. Esse RC, Lowery JA, Tamorria CR, Sieger GM (1964a) Tetracycloxides. I. A new class of tetracycline derivatives. J Am Chem Soc 86:3874–3875Google Scholar
  47. Esse RC, Lowery JA, Tamorria CR, Sieger GM (1964 b) Tetracycloxides. II. Transformations at the C-4 position. J Am Chem Soc 86:3875–3877Google Scholar
  48. Fabre J, Milek E, Kalfopoulos P (1971) La cinétique des tétracyclines chez l’homme. I. Absorption digestive et concentrations sériques. Schweiz Med Wochenschr 101:593–598Google Scholar
  49. Fields TL, Kende AS, Boothe JH (I960) Total synthesis of tetracyclines. II. Stereospecific synthesis of (±)-dedimethylamino-6-demethyl-6,12a-dideoxy-7-chlorotetracycline. J AmChem Soc 82:1250–1251Google Scholar
  50. Fields TL, Kende AS, Boothe JH (1961) Total synthesis of tetracyclines. V. The stereospecific elaboration of the tetracycline ring system. J Am Chem Soc 83:4612–4618Google Scholar
  51. Fourtillan JB, Lefèbvre MA (1980) Corrélations structure-activité dans la famille des te-tracyclines. Nouv Presse Med 9:64–10PubMedGoogle Scholar
  52. Free SM, Wilson JW (1964) A mathematical contribution to structure-activity studies. J Med Chem 1:395–399Google Scholar
  53. Glatz B, Helmchen G, Muxfeldt H, Porcher H, Prewo R, Senn J, Stezowski JJ, Stojda RJ, White DR (1979) A total synthesis and structural aspects of racemic 8-oxygenated tetracyclines. J Am Chem Soc 101:2171–2181Google Scholar
  54. Gottstein WJ, Minor WF, Cheney LC (1959) Carboxamido derivatives of the tetracyclines. J Am Chem Soc 81:1198–1201Google Scholar
  55. Granatek ES, Kaplan MA, Buckwalter FH (1963) N-(3-phthalidyl)-tetracycline, a new carboxamido derivative of tetracycline. J Med Chem 6:202PubMedGoogle Scholar
  56. Green A, Boothe JH (1960) Chemistry of the tetracycline antibiotics. III. 12a-Deoxytetracycline. J Am Chem Soc 82:3950–3953Google Scholar
  57. Green A, Wilkinson RG, Boothe JH (1960) Chemistry of the tetracycline antibiotics. II. Bromination of dedimethylaminotetracyclines. J Am Chem Soc 82:3946–3950Google Scholar
  58. Gulbis J, Everett W Jr (1975) A 13C Nuclear magnetic resonance analysis of the metal binding site in tetracycline. J Am Chem Soc 97:6248–6249PubMedGoogle Scholar
  59. Gulbis J, Everett W Jr (1976) Metal binding characteristics of tetracycline derivatives in DMSO solution. Tetrahedron 32:913–917Google Scholar
  60. Gurevich AI, Karapepetyan MG, Kolosov MN, Korobko VG, Onoprienko VV, Popravko SA, Shemyakin MM (1967) Synthesis of 12a-deoxy-5a,6-anhydrotetracycline. The first total synthesis of the naturally occurring tetracycline. Tetrahedron Lett 131–134Google Scholar
  61. Hirokawa S, Okaya Y, Lovell FM, Pepinsky R (1959) Crystal structure of aureomycin hydrochloride. Z Krist 112:439–464Google Scholar
  62. Hlavka JJ, Bitha P (1966) Photochemistry. IV. A photodeamination. Tetrahedron Lett 32:3843–3846Google Scholar
  63. Hlavka JJ, Boothe JH (1973) The tetracyclines. Arzneimittelforsch 17:210–240Google Scholar
  64. Hlavka J J, Buyske DA (1960) Radioactive 7-iodo-6-deoxy tetracycline in tumor tissue. Nature 186:1064–1065PubMedGoogle Scholar
  65. Hlavka JJ, Krazinski HM (1963) The 6-deoxytetracyclines. VI. A photochemical transformation. J Org Chem 28:1422–1423Google Scholar
  66. Hlavka JJ, Schneller A, Krazinski H, Boothe JH ( 1962 a) The 6-deoxy tetracyclines. III. Electrophilic and nucleophilic substitution. J Am Chem Soc 84:1426–1430Google Scholar
  67. Hlavka JJ, Krazinski HM, Boothe JH ( 1962 b) The 6-deoxy tetracyclines. IV. A photochemical displacement of a diazonium group. J Org Chem 27:3674–3675Google Scholar
  68. Hlavka JJ, Bitha P, Boothe JH (1968) 4-Hydroxypretetramids. J Am Chem Soc 90:1034–1037PubMedGoogle Scholar
  69. Hochstein FA, Stephens CR, Conover LH, Regna PP, Pasternack R, Gordon PN, Pilgrim FJ, Brunings KJ, Woodward RB (1953) The structure of terramycin. J Am Chem Soc 75:5455–5475Google Scholar
  70. Hochstein FA, Schach von Wittenau M, Tanner FW, Murai K (1960) 2-Acetyl-2-decarboxamidooxytetracycline. J Am Chem Soc 82:5934–5937Google Scholar
  71. Holmlund CE, Andres WW, Shay AJ (1959) Chemical hydroxylation of 12a-deoxytetracycline. J Am Chem Soc 81:4748–4750Google Scholar
  72. Hošt’álek Z, Blumauerová M, Vanek Z (1914) Genetic problems of the biosynthesis of tetracycline antibiotics. Adv Biochem Eng 3:13–67Google Scholar
  73. Hüttenrauch R, Keiner I (1966) Epimerisierung von Mannich-Basen der Tetracyclin-Antibiotika. Naturwissenschaften 53:552Google Scholar
  74. Hughes RE, Muxfeldt H, Dreele RB von (1971) Conformation of tetracycline ring systems. Structure of 5,12a-diacetyloxytetracycline. J Am Chem Soc 93:1037–1038PubMedGoogle Scholar
  75. Hughes DW, Wilson WL, Butterfield AG, Pound NJ (1974) Stability of rolitetracycline in aqueous solution. J Pharm Pharmacol 26:79–80PubMedGoogle Scholar
  76. Hughes LJ, Stezowski JJ, Hughes RE (1979) Chemical structural properties of tetracycline derivatives. 7. Evidence for the coexistence of the zwitterionic and nonionized forms of the free base in solution. J Am Chem Soc 101:7655–7657Google Scholar
  77. Hussar DA, Niebergall PJ, Sugita ET, Doluisio JT (1968) Aspects of the epimerization of certain tetracycline derivatives. J Pharm Pharmacol 20:539–546PubMedGoogle Scholar
  78. Jarowski CI (1963) Paper presented at the Sixth Pan American congress of pharmacy and biochemistry, Mexico City, December 1963Google Scholar
  79. Jogun KH, Stezowski JJ (1976) Chemical-structural properties of tetracycline derivatives. 2. Coordination and conformation aspects of oxytetracycline metal ion complexation. J Am Chem Soc 98:6018–6026PubMedGoogle Scholar
  80. Kelly RG (1964) Determination of anhydrotetracycline and 4-epianhydrotetracycline in a tetracycline mixture. J Pharm Sci 53:1551–1552PubMedGoogle Scholar
  81. Kende AS, Fields TL, Boothe JH, Kushner S (1961) Total synthesis of tetracyclines. IV. Synthesis of an anhydrotetracycline derivative. J Am Chem Soc 83:439–449Google Scholar
  82. Kirchlechner R (1981) Synthese von 6-Oxatetracyclin, einem weiteren Heteroanalogen Tetracyclin. Tetrahedron Lett 22/16:1497–1500Google Scholar
  83. Kirchlechner R, Rogalski W (1980) Synthesis of 6-thiatetracycline, a highly active analogue of the antibiotic tetracycline. Tetrahedron Lett 21:247–250Google Scholar
  84. Kirchlechner R, Seubert J (1982) Synthese von 6-Thiaminocyclin, einem Thiaanalogen des Antibiotikums Minocyclin. Arch Pharm 315:519–525Google Scholar
  85. Kirchlechner R, Rogalski W, Dingeldein E, Wahlig H (1977) Thiatetracyclines, a new class of totalsynthetic tetracyclines. XVII. Interscience conference on antimicrobial agents and chemotherapy, New York, Oct 1977, Abstract 70Google Scholar
  86. Kollat P, Stezowski JJ (1982) Nonionized 5a-epi-6-oxatetracycline free base. Acta Cryst B 38:2531–2533Google Scholar
  87. Korst JJ (1972a) In 2-Stellung substituierte Tetracycline. Deutsche Offenlegungsschrift (Patent) 2065:149Google Scholar
  88. Korst JJ (1972 b) Verfahren zur Herstellung von 2-decarboxamido-2-iminotetracyclinen, bzw. Ihren Säureadditionssalzen oder Metallsalzen. Deutsche Offenlegungsschrift (Patent) 2049:941Google Scholar
  89. Korst JJ, Johnston JD, Butler K, Bianco EJ, Conover LH, Woodward RB (1968) The total synthesis of d,l-6 demethyl-6-deoxytetracycline. J Am Chem Soc 90:439–457Google Scholar
  90. Koschel K. Hartmann G, Kersten W, Kersten H (1966) Die Wirkung des Chromomycins und einiger Anthracyclinantibiotica auf die DNA-abhängige Nucleinsäure-Synthese. Biochem Z 244:76–86Google Scholar
  91. Last JA (1969) Studies on the binding of tetracycline to ribosomes. Biochim Biophys Acta 195:506–514PubMedGoogle Scholar
  92. MacDonald H, Kelly RG, Allen ES, Noble JF, Kanegis LA (1973) Pharmacokinetics studies on minocycline in man. Clin Pharmacol Ther 14:852–861PubMedGoogle Scholar
  93. Martell MJ, Boothe JH (1967) The 6-deoxytetracycline. VII. Alkylated aminotetracyclines possessing unique antibacterial activity. J Med Chem 10:44–46PubMedGoogle Scholar
  94. Martell MJ Jr, Ross AS, Boothe JH ( 1967 a) The 6-deoxytetracycline. IX. Imidomethylation. J Med Chem 10:359–363Google Scholar
  95. Martell MJ Jr, Ross AS, Boothe JH ( 1967 b) The 6-deoxytetracyclines. VIII. Acylaminomethylamides. J Med Chem 10:485–486Google Scholar
  96. Martell MJ Jr, Ross AS, Boothe JH (1967 c) The dehydrotetracyclines. I. Epimerization at C-6. J Am Chem Soc 89:6780–6781Google Scholar
  97. Martin W, Hartung H, Urbach H, Dürckheimer W (1973) Synthesen in der Tetracyclinreihe. I. Totalsynthese von d,l-7-Chlor-6-desoxytetracyclinen und d,l-7-Chlor-6-desmethyl-6-desoxytetracyclinen der natürlichen, der 5a-epi- und der 6-epi-Reihe. Tetrahedron Lett 3513–3516Google Scholar
  98. McCapra F, Scott AI, Delmotte P, Delmotte-Plaquée J (1964) The constitution of monorden, an antibiotic with tranquilising action. Tetrahedron Lett 869–875Google Scholar
  99. McCormick JRD, Jensen ER (1968) Biosynthesis of tetracyclines. J Am Chem Soc 90:7126–7127PubMedGoogle Scholar
  100. McCormick JRD, Fox SM, Smith LL, Bitler BA, Reichenthal J, Origoni VE, Muller WH, Winterbottom R, Doerschuk AP (1956) On the nature of the reversible isomerizations occurring in the tetracycline family. J Am Chem Soc 78:3547–3548Google Scholar
  101. McCormick JRD, Fox SM, Smith LL, Bitler BA, Reichenthal J, Origoni VE, Muller WH, Winterbottom R, Doerschuk AP (1957) Studies of the reversible epimerization occurring in the tetracycline family. The preparation, properties and proof of structure of some 4-epitetracyclines. J Am Chem Soc 79:2849–2858Google Scholar
  102. McCormick JRD, Miller PA, Growich JA, Sjolander NO, Doerschuk AP (1958) Two new tetracycline-related compounds: 7-chloro-5a(11a)-dehydrotetracycline and 5a-epi-tetracycline. A new route to tetracycline. J Am Chem Soc 80:5572–5573Google Scholar
  103. McCormick JRD, Jensen ER, Miller PA, Doerschuk AP (1960) The 6-deoxy tetracyclines. Further studies on the relationship between structure and antibacterial activity in the tetracycline-series. J Am Chem Soc 82:3381–3386Google Scholar
  104. McCormick JRD, Winterbottom R, Bitha P (1965) Novel 7,11a-dihalotetracyclines and the process of preparing them. U.S. Patent 3,226, 435Google Scholar
  105. McMurry L, Petrucci RE, Levy SB (1980) Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli. Proceedings of the national academy of sciences 77:3974–3977Google Scholar
  106. McMurry L, Cullinane JC, Levy SB (1982) Transport of the lipophilic analog minocycline differs from that of tetracycline in susceptible and resistant Escherichia coli strains. Antimicrob Agents Chemother 5:791–799Google Scholar
  107. Miller MW, Hochstein FA (1962) Isolation and characterization of two new tetracycline antibiotics. J Org Chem 27:2525–2528Google Scholar
  108. Mitscher LA (1978) The chemistry of the tetracycline antibiotics. Med Res Ser 9Google Scholar
  109. Mitscher LA, Bonacci AC, Sokoloski TD (1968) Circular dichroism and solution conformation of the tetracycline antibiotics. Antimicrob Agents Chemother 78–86Google Scholar
  110. Mitscher LA, Bonacci AC, Slater-Eng B, Hacker AW, Sokoloski TD (1969) Interaction of various tetracyclines with metallic cations in aqueous solutions as measured by circular dichroism. Antimicrob Agents Chemother 111–115Google Scholar
  111. Mitscher LA, Rosenbrook WM Jr, Andres WW, Egan RS, Schenck J, Juvarkar JV (1970) Structure of chelocardin, a novel tetracycline antibiotic. Antimicrob Agents Chemother 38–41Google Scholar
  112. Mitscher LA, Slater-Eng B, Sokoloski TD (1972) Circular dichroism measurements of the tetracyclines. IV. 5-Hydroxylated derivatives. Antimicrob Agents Chemother 2:66–72PubMedGoogle Scholar
  113. Money T, Scott AI (1968) Recent advances in the chemistry and biochemistry of tetracyclines. Prog Org Chem 7:1–34Google Scholar
  114. Muxfeldt H (1962) Synthesen der Tetracyclin-Reihe. Angew Chem 74/13:443–452Google Scholar
  115. Muxfeldt H, Kreutzer A (1961) Tetracycline. II. Synthese des Desdimethylamino-anhydroaureomycins. Chem Ber 94:881–893Google Scholar
  116. Muxfeldt H, Rogalski W (1965) Tetracyclines. V. A total synthesis of (±)-6-deoxy-6-demethyltetracycline. J Am Chem Soc 87:933–934PubMedGoogle Scholar
  117. Muxfeldt H, Hardtmann G, Kathawala F, Vedejs E, Mooberry JB (1968) Tetracyclines. VII. Total synthesis of dl-Terramycin. J Am Chem Soc 90:6534–6536PubMedGoogle Scholar
  118. Muxfeldt H, Döpp H, Kaufmann JE, Schneider J, Hansen PE, Sasaki A, Geiser T (1973) Totalsynthese des Anhydro-aureomycins. Angew Chem Int Ed Engl 12:508–510Google Scholar
  119. Muxfeldt H, Haas G, Hardtmann G, Kathawala F, Mooberry JB, Vedejs E (1979) Tetracyclines. 9. Total synthesis of dl-Terramycin. J Am Chem Soc 101:689–701Google Scholar
  120. Neu HC (1978) Symposium on the tetracyclines: a major appraisal. Bulletin NY Acad Med 54:141–145Google Scholar
  121. Nikaido H, Nakae T (1979) The outer membrane of gram-negative bacteria. Adv Microb Physiol 20:163–250PubMedGoogle Scholar
  122. Notari RE (1973) Pharmacokinetics and molecular modification: implications in drug design and evaluation. J Pharm Sci 62:865–880PubMedGoogle Scholar
  123. Oliver TJ, Prokop JF, Bower RR, Otto RH (1962) Chelocardin, a new broad-spectrum antibiotic. I. Discovery and biological properties. Antimicrob Agents Chemother 583–591Google Scholar
  124. Pelcak E, Dornbush A (1948) Aureomycin - a new antibiotic. Ann NY Acad Sci 51:218PubMedGoogle Scholar
  125. Peradejordi F, Martin AN, Cammarata A (1971) Quantum chemical approach to structure-activity relationships of tetracycline antibiotics. J Pharm Sci 60:576–582PubMedGoogle Scholar
  126. Petisi J, Spencer JL, Hlavka JJ, Boothe JH (1962) 6-Deoxytetracyclines. III. Nitrations and subsequent reactions. J Med Pharm Chem 5:538–546Google Scholar
  127. Prewo R, Stezowski JJ (1977) Chemical structural properties of tetracycline derivatives. 3. The integrity of the conformation of the nonionized free base. J Am Chem Soc 99:1117–1121PubMedGoogle Scholar
  128. Prewo R, Stezowski JJ (1980) Chemical-structural properties of tetracycline derivatives. 9. 7-Chlorotetracycline derivatives with modified stereochemistry. J Am Chem Soc 102:7015–7020Google Scholar
  129. Prewo R, Stezowski JJ, Kirchlechner R (1980) Chemical-structural properties of tetracycline derivatives. 10. The 6-thiatetracyclines. J Am Chem Soc 102:7021–7026Google Scholar
  130. Purcell WP, Bass GE, Clayton JM (1973) Strategy of drug design, a molecular guide to biological activity. Wiley, New YorkGoogle Scholar
  131. Purich SD, Colaizzi JL, Poust RI (1973) pH-partition behaviour of amino acid-like ß-lactum antibiotics. J Pharm Sci 62:545–549PubMedGoogle Scholar
  132. Redin GS (1966) Antibacterial activity in mice of minocycline, a new tetracycline. Antimicrob Agents Chemother 371–376Google Scholar
  133. Remmers EG, Sieger GM, Doerschuk AP (1963) Some observations on the kinetics of the C-4 epimerization of tetracycline. J Pharm Sci 52:752–756PubMedGoogle Scholar
  134. Rennhard HH, Blackwood RK, Stephens CR (1961) Fluortetracyclines. I. Perchloryl fluoride studies in the tetracycline series. J Am Chem Soc 83:2775–2777Google Scholar
  135. Rigler NE, Bag SP, Leyden DE, Sudmeier JL, Reilley CN (1965) Determination of a protonation scheme of tetracycline using nuclear magnetic resonance. Anal Chem 37:872–875PubMedGoogle Scholar
  136. Rogalski W (1978) Structure-activity relationships of thiatetracyclines. XVIII. Interscience conference on antimicrobial agents and chemotherapy, Atlanta, Oct 1978Google Scholar
  137. Russell AD, Ahonkhai I (1982) Antibacterial activity of a new thiatetracycline antibiotic, thiacycline, in comparison with tetracycline, doxycycline and minocycline. J Antimicrob Chemother 9:445–449PubMedGoogle Scholar
  138. Schach von Wittenau M, Beereboom JJ, Blackwood RK, Stephens CR (1962) 6-Deoxytetracyclines. III. Stereochemistry at C-6. J Am Chem Soc 84:2645–2647Google Scholar
  139. Schach von Wittenau M, Hochstein FA, Stephens CR (1963) Tautomerism of 5a-11a-dehydro-7-chlorotetracycline. Preparation of 5-alkoxy-7-chloranhydrotetracyclines. J Org Chem 28:2454–2456Google Scholar
  140. Schach von Wittenau M, Blackwood RK, Conover LH, Glavert RH, Woodward RB (1965) The stereochemistry at C-5 in Oxytetracycline. J Am Chem Soc 87:134–135Google Scholar
  141. Schach von Wittenau M, Blackwood RK (1966) Proton magnetic resonance; spectra of tetracyclines. J Org Chem 31:613–615Google Scholar
  142. Schwarz JSP, Applegate HE (1967) Chemistry of tetracyclines. II. Allotetracycline and allooxytetracycline. J Org Chem 32:1241–1243Google Scholar
  143. Schwarz JSP, Applegate HE, Bouchard JL, Weisenborn FL (1967) Chemistry of tetracyclines. I. Mercuric acetate oxidation of tetracycline. J Org Chem 32:1238–1241Google Scholar
  144. Scott AI, Bedford CT (1962) Simulation of the biosynthesis of tetracyclines. A partial synthesis of tetracycline from anhydroaureomycin. J Am Chem Soc 84:2271–2274Google Scholar
  145. Shu P (1966) Oxidative preparation of 9-hydroxytetracyclines. J Am Chem Soc 88:4529–4530Google Scholar
  146. Siedel W, Söder A, Lindner F (1958) Die Aminomethylierung der Tetracycline. Zur Chemie des Reverin. Münch Med Wochenschr 17:661–663Google Scholar
  147. Sinclair AC, Schenck JR, Post GG, Cardinal EV, Burokas S, Fricke HH (1962) Chelocardin, a new broad-spectrum antibiotic. II. Isolation and characterization. Antimicrob Agents Chemother 592–595Google Scholar
  148. Spencer JL, Hlavka JJ, Petisi J, Krazinski HM, Boothe JH (1963) 6-Deoxytetracyclines. V. 7,9-Disubstituted products. J Med Chem 6:405–407PubMedGoogle Scholar
  149. Steigbigel NH, Reed CW, Finland M (1968) Susceptibility of common pathogenic bacteria to seven tetracycline antibiotics in vitro. Am J Med Sci 255:179–195PubMedGoogle Scholar
  150. Stephens CR (1962) U.S. Patent 3028 409 (assigned to Chas. Pfizer and Co., Inc.)Google Scholar
  151. Stephens CR, Conover LH, Pasternack R, Hochstein FA, Moreland WT, Regna PP, Pilgrim FJ, Brunings KJ, Woodward RB (1954) The structure of aureomycin. J Am Chem Soc 76:3568–3575Google Scholar
  152. Stephens CR, Bianco EJ, Pilgrim FJ (1955) A new reagent for dehydrating primary amides under mild conditions. J Am Chem Soc 77:1701–1702Google Scholar
  153. Stephens CR, Conover LH, Gordon PN, Pennington FC, Wagner RL, Brunings KJ, Pilgrim FJ (1956) Epitetracycline - the chemical relationship between tetracycline and “Quatrimycin”. J Am Chem Soc 78:1515–1516Google Scholar
  154. Stephens CR, Beereboom JJ, Rennhard HH, Gordon PN, Murai K, Blackwood RK, Schach von Wittenau M (1963) 6-Deoxytetracyclines. IV. Preparation, C-6 stereochemistry, and reactions. J Am Chem Soc 85:2643–2652Google Scholar
  155. Stezowski JJ (1976) Chemical-structural properties of tetracycline derivatives. 1. Molecular structure and conformation of the free base derivatives. J Am Chem Soc 98:6012–6018PubMedGoogle Scholar
  156. Stezowski JJ (1977) Chemical-structural properties of tetracycline antibiotics. 5. Ring A tautomerism involving the protonated amide substituent as observed in the crystal structure of a-6-deoxytetracycline hydrohaldes. J Am Chem Soc 99:1122–1129PubMedGoogle Scholar
  157. Stezowski JJ (1982) Steric effects - Intramolecular information transfer in tetracycline antibiotics. In: Náray-Szabó (ed) Proceedings of the symposium on steric effects in biomolecules. Academia IAI Kiadó, Budapest, 1982, pp 3–13Google Scholar
  158. Stezowski JJ, Prewo R (1980) Chemical-structural properties of tetracycline derivatives. Abstr Pap Am Chem Soc Meet Phys 179:87Google Scholar
  159. Takeuchi Y, Buerger MJ (1960) The crystal structure of Terramycin hydrochloride. Proc Natl Acad Sci USA 46:1366–1370PubMedGoogle Scholar
  160. Tamorria CR, Esse RC (1965) Alkoxyalkyltetracyclines. J Med Chem 8:870–872PubMedGoogle Scholar
  161. Teare EL, Bakhtiar M, Selwyn S (1981) Comparative in vitro studies of a new thiatetracycline and three existing tetracyclines. Drugs Exp Clin Res VII (3):307–311Google Scholar
  162. Terada H, Inagi T (1975) Proposed partition mechanism of tetracycline. Chem Pharm Bull 23:1960–1968PubMedGoogle Scholar
  163. Toon S, Rowland M (1979) Quantitative structure pharmacokinetic activity relationships with some tetracyclines. J Pharm Pharmacol [Suppl] 31:43 PGoogle Scholar
  164. Tritton TR (1977) Ribosome-tetracycline interactions. Biochemistry 16:4133–4138PubMedGoogle Scholar
  165. Tubaro E, Banci F (1964) The pharmacology of chlormethylenecycline, a new chlortetracycline. Arzneimittelforsch 5:95–100Google Scholar
  166. Tute MS (1975) Lipophilicity. Chem Ind (Lond) 100–105Google Scholar
  167. Ungethüm W, Dingeldein E, Pabst J, Leopold G, Diekmann H (1980) Clinical pharmaco-kinetics of EMD 33 330, a new totally synthetic tetracycline. World conference on clinical pharmacology and therapuetics, London, 3rd-9th August 1980. Abstract No. 0438Google Scholar
  168. Urbach H, Hartung H, Martin W, Dürckheimer W (1973) Synthesen in der Tetracyclinreihe. II. Totalsynthese von dl-4-Amino-7-chlor-2-N-methylcarbamyl-2-descarbamyl-4- desdimethylamino-6-desmethyl-6-desoxytetracycline. Tetrahedron Lett 1973:4907–4910Google Scholar
  169. Valcavi U, Campanella G, Pacini N (1963) Pirazolderivati della tetracyclina e clorotetracyclina. Gazz Chim Ital 93:916–928Google Scholar
  170. Valcavi U, Brandt A, Corsi GB, Minoja F, Pascucci G (1981) Chemical modifications in the tetracycline series. J Antibiotics 34:34–39Google Scholar
  171. Vaněk Z, Cudlin J, Blumauerova M, Hošt’álek Z (1974) How many genes are required for the synthesis of chlortetracycline? Folia Microbiol (Prague) 16:225–240Google Scholar
  172. van den Hende JH (1965) The crystal and molecular structures of 7-chloro- and 7-bromo-4-hydroxytetracycloxide. J Am Chem Soc 87:929–931Google Scholar
  173. von Dreele RB, Hughes RE (1971) Crystal and molecular structure of 5,12a-diacetyloxy-tetracycline. J Am Chem Soc 93:7290–7296Google Scholar
  174. Welling PG, Koch PA, Lau CC, Craig WA (1977) Bioavailability of tetracycline and doxycycline in fasted and nonfasted subjects. Antimicrob Agents Chemother 11:462–469PubMedGoogle Scholar
  175. Wilkinson RG, Boothe JH (1961) Deutsches Patentamt (GP) Auslegeschrift 1, 1088, 481: Verfahren zur Herstellung neuer Verbindungen der TetracylinreiheGoogle Scholar
  176. Williamson DE, Everett W Jr (1975) A proton nuclear magnetic resonance study of the site of metal binding in tetracycline. J Am Chem Soc 97:2397–2405PubMedGoogle Scholar
  177. Woodward RB (1963) The total synthesis of a tetracycline. Pure Appl Chem 6:561–573Google Scholar

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© Springer-Verlag Berlin Heidelberg 1985

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  • W. Rogalski

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