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Chapter 3 : Discovery and Industrialization of Therapeutically Important Tetracyclines

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Discovery and Industrialization of Therapeutically Important Tetracyclines, Page 1 of 2

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Abstract:

The discovery and clinical use of the tetracycline family of antibiotics emerged from efforts in research and development that were a leap of faith for the times in the 1930s. The search for antibiotic-producing microorganisms began with the discovery of penicillin, and in an effort to study therapeutic substances from soil microorganisms. Methacycline and doxycycline were successful as second-generation tetracyclines in the world antibiotic market. Tigecycline shares the same antibacterial properties of its antecedent tetracyclines; however, unlike the previous generations of tetracyclines, oral bioavailability has been poor thereby restricting tigecycline to intravenous use. The tetracyclines were some of the first antibiotics discovered and mass marketed throughout the world for the treatment of a broad spectrum of infectious disease states and represent a chronological progression of the discovery of natural products as drugs to semisynthetic derivatives of better potency and properties. It is hoped that a novel semi-synthetic tetracycline antibiotic will be available for use against bacterial pathogens in the early 21st century.

Citation: Nelson M, Projan S. 2005. Discovery and Industrialization of Therapeutically Important Tetracyclines, p 29-38. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch3

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Figure 1

Professor Benjamin Minge Duggar (1872–1956), discoverer of chlortetracycline.

Citation: Nelson M, Projan S. 2005. Discovery and Industrialization of Therapeutically Important Tetracyclines, p 29-38. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch3
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Figure 2

The chemical structures, trade name, and common name of chlortetracycline (I), oxytetracycline (II), and tetracycline (III).

Citation: Nelson M, Projan S. 2005. Discovery and Industrialization of Therapeutically Important Tetracyclines, p 29-38. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch3
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Figure 3

The biosynthetic pathway of the tetracyclines producing oxytetracycline (IX) and tetracycline (X) by species.

Citation: Nelson M, Projan S. 2005. Discovery and Industrialization of Therapeutically Important Tetracyclines, p 29-38. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch3
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Figure 4

The semisynthetic pathway chosen by the Chas. Pfizer Co. for the production of methacycline (I) and doxycycline (II) and the pathway chosen by American Cyanamid for the production of minocycline (III) and the glycylcyclines (IV).

Citation: Nelson M, Projan S. 2005. Discovery and Industrialization of Therapeutically Important Tetracyclines, p 29-38. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch3
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Figure 5

Semisynthetic pathway of methacycline (IV), doxycycline (V), and 6-epi doxycycline (VI) achieved by the Chas. Pfizer Co.

Citation: Nelson M, Projan S. 2005. Discovery and Industrialization of Therapeutically Important Tetracyclines, p 29-38. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch3
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Figure 6

Semisynthetic pathway of sancycline (II), minocycline (VII), and tigecycline (VII) achieved by the American Cyanamid Co. (Wyeth).

Citation: Nelson M, Projan S. 2005. Discovery and Industrialization of Therapeutically Important Tetracyclines, p 29-38. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch3
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Figure 7

P. E. Sum led the chemistry team at Wyeth responsible for the glycylcyclines and tigecycline.

Citation: Nelson M, Projan S. 2005. Discovery and Industrialization of Therapeutically Important Tetracyclines, p 29-38. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch3
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References

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1. Blackwood, R. K.,, J. J. Beereboom,, H. H. Rennhard,, M. Schach von Wittenau,, and C. R. Stephens. 1961. 6-Methylenetetracyclines. A new class of tetracycline antibiotics. J. Am. Chem. Soc. 83: 2773 2775.
2. Blackwood, R. K.,, J. J. Beereboom,, H. H. Rennhard,, M. Schach von Wittenau,, and C. R. Stephens. 1963. 6-Methylenetetracyclines. III. Preparation and properties. J. Am. Chem. Soc. 85: 3943 3953.
3. Boothe, J. H.,, A. S. Kende,, T. L. Fields,, and R. G. Wilkinson. 1959. Total synthesis of tetracyclines. I. (+/-)-Dedimethylamino- 12a-deoxy-6-demethylanhydrochlortetracycline. J. Am. Chem. Soc. 81: 1006 1007.
4. Boothe, J. H.,, J. J. Hlavka,, J. P. Petisi,, and J. L. Spencer. 1960. 6-Deoxytetracyclines. I. Chemical modification by electrophilic substitution. J. Am. Chem. Soc. 82: 1253 1254.
5.Centers for Disease Control and Prevention. 2001. Update: Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy. Centers for Disease Control and Prevention Morb. Mortal. Wkly. Rep. 50: 909919.
6. Chiyowski, L. N. 1973. Effectiveness of antibiotics applied as postinoculation sprays against clover phyllody and aster yellows. J. Plant Sci. 53: 87 91.
7. Church, R. F. R.,, R. E. Schaub,, and M. J. Weiss. 1971. Synthesis of 7-dimethylamino-6-demethyl-6-deoxytetracycline (Minocycline) via 9-nitro-6-demethyl-6-deoxytetracycline. J. Org. Chem. 36: 723 725.
8. Duggar, B. M. 1905. The principles of mushroom growing and mushroom spawn making. USDA Bureau Plant Industry Bull. 35: 1 60.
9. Duggar, B. M. 1948. Aureomycin: a product of the continuing search for new antibiotics. Ann. New York Acad. Sci. USA 51: 171 181.
10. Felekidis, A.,, M. Goblet-Stachow,, J. F. Liegeois,, B. Pirotte,, J. Delarge,, A. Demonceau,, M. Fontaine,, A. F. Noels,, I. T. Chizhevsky,, T. V. Zinevich,, V. I. Bregadze,, F. M. Dolgushin,, A. I. Yanovsky,, and T. Y. Struchkov. 1997. Ligand effects in the hydrogenation of methacycline to doxycycline and epi-doxycycline catalyzed by rhodium complexes. Molecular structure of the key catalyst [closo-3,3-( η2,3-C 7H 7CH 2)-3,1,2-RhC 2B 9H 11]. J. Organometallic Chem. 536/ 537: 405 412.
11. Findlay, A. C.,, G. L. Hobby,, S. Y. Pan,, J. B. Regna,, D. B. Routien,, D. B. Seeley,, G. M. Shull,, B. A. Sobin,, I. A. Solomens,, J. W. Vinson,, and J. H. Kane. 1950. Terramycin, a new antibiotic. Science 111: 85.
12. Golub, L. M.,, T. Sorsa,, H. M. Lee,, S. Ciancio,, D. Sorbi,, N. S. Ramamurthy,, B. Gruber,, T. Salo,, and Y. T. Konttinen. 1995. Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva. J. Clin. Periodontol. 22: 100 109.
13. Hlavka, J.,, A. Schneller,, H. Krazinski,, and J. H. Boothe. 1962. The 6-deoxytetracyclines. III. Electrophilic and nucleophilic substitution. J. Am. Chem. Soc. 84: 1426 1430.
14. Hochstein, F. A.,, C. R. Stephens,, L. H. Conover,, P. P. Regna,, R. Pasternack,, K. J. Brunings,, and R. B. Woodward. 1952. Terramycin. VIII. The structure of Terramycin. J. Am. Chem. Soc. 74: 3708 3709.
15. Hochstein, F. A.,, C. R. Stephens,, L. H. Conover,, P. P. Regna,, R. Pasternack,, P. N. Gordon,, F. J. Pilgrim,, K. J. Brunings,, and R. B. Woodward. 1953. The structure of Terramycin. J. Am. Chem. Soc. 75: 5455 5475.
16. Hostelak, Z.,, M. Blumauerova,, and Z. Vanek,. 1979. Tetracycline antibiotics, p. 293 353. In A. H. Rose (ed.), Economic Microbiology, vol. 3. Secondary Products of Metabolism. Academic Press, London, United Kingdom.
17. Hunter, I. S.,, and R. A. Hill,. 1997. Tetracyclines, p. 659 682. In W. R. Strohl (ed.), Biotechnology of Antibiotics, 2nd Edition, vol. 82, Drugs and Pharmaceutical Sciences, Marcel Dekker, Inc. New York, N.Y.
18. Hutchings, B. L.,, C. W. Waller,, R. W. Broschard,, C. F. Wolf,, P. W. Fryth,, and J. H. Williams. 1952. Degradation of Aureomycin. V. Aureomycinic acid. J. Am. Chem. Soc. 74: 4980.
19. Hutchinson, C. R., 1981. The biosynthesis of tetracycline and anthracycline antibiotics, p. 1 11. In J. W. Corcoran, (ed.), Antibiotics, vol. IV, Biosynthesis. Springer, Berlin Heidelberg, New York.
20. Johnson, S. E.,, G. C. Klein,, G. P. Schmid,, and J. C. Feeley. 1984. Susceptibility of the Lyme disease spirochete to seven antimicrobial agents. Yale J. Biol. Med. 57: 549 553.
21. Kirby, W. M. M.,, C. E. Roberts, Jr., and R. E. Burdick. 1961. Comparison of two new tetracyclines with tetracycline and demethylchlortetracycline. Antimicrob. Agents Chemother. 286 292.
22. Kloppenburg, M.,, B. A. C. Dijkmans,, C. L. Verweij,, and F. C. Breedveld. 1996. Inflammatory and immunological parameters of disease activity in rheumatoid arthritis patients treated with minocycline. Immunopharmacology 31: 163 169.
23. Martell, M. J.,, and J. H. Boothe. 1967. The 6-deoxytetracyclines. VII. Alkylated aminotetracyclines possessing unique antibacterial activity. J. Med. Chem. 10: 44 46.
24. McCormick, J. R. D.,, N. O. Sjolander,, U. Hirsch,, E. R. Jensen,, and A. P. Doerschuk. 1957. A new family of antibiotics: the demethyltetracyclines. J. Am. Chem. Soc. 79: 4561 4563.
25. McCormick, J. R. D.,, N. O. Sjolander,, S. Johnson,, and A. P. Doershuk. 1959. Biosynthesis of tetracyclines. II. Simple defined media for growth of Streptomyces aureofaciens and elaboration. J. Bacteriol. 77: 475 477.
26. McCormick, J. R. D.,, E. R. Jensen,, P. A. Miller,, and A. P. Doerschuk. 1960. The 6-deoxytetracyclines. Further studies on the relationship between structure and antibacterial activity in the tetracycline series. J. Am. Chem. Soc. 82: 3381 3386.
27. McCormick, J. R. D., 1966. Biosynthesis of the tetracyclines: an integrated biosynthetic scheme (Part I and II), p. 556 . In M. Herold, and Z. Gabriel (ed.), Antibiotics. Advances in Research, Production and Clinical Use. Butterworths, London, United Kingdom.
28. Miller, P. A.,, J. R. D. McCormick,, and A. P. Doershuk. 1956. Studies of chlorotetracycline biosynthesis and the preparation of chlorotetracycline-C14. Science 123: 1030 1031.
29. Nadelman, R. B.,, J. Nowakowski,, D. Fish,, R. C. Falco,, K. Freeman,, D. McKenna,, P. Welch,, R. Marcus,, M. E. Aguero-Rosenfeld,, D. T. Dennis,, and G. P. Wormser. 2001. Tick Bite Study Group. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N. Engl. J. Med. 345: 79 84.
30. Nakazawa, S.,, H. Ono,, T. Nishino,, S. Kuwahara,, and S. Goto. 1970. In vitro and in vivo laboratory evaluation of minocycline— a new tetracycline derivative, p. 353 360. In Progr. Antimicrob. Anticancer Chemother., Proceedings of the International Congress on Chemotherapy, 6th Meeting Date 1969, University Park Press, Baltimore, Md.
31. Noble, J. F., 1972. Minocycline. Laboratory and clinical studies, p. 4 15. In E. Lauschner (ed.), Minocyclin-Symposium. Georg Thieme, Stuttgart, Germany.
32.. Pearson, M. 1969. The Million Dollar Bugs. Putnam, New York, N.Y.
33. Petersen, P. J.,, N. V. Jacobus,, W. J. Weiss,, P. E. Sum,, and R. T. Testa. 1999. In vitro and in vivo antibacterial activities of a novel glycylcycline, the 9-t-butylglycylamido derivative of minocycline (GAR-936). Antimicrob. Agents Chemother. 43: 738 744.
34. Pirotte, B.,, A. Felekidis,, M. Fontaine,, A. Demonceau,, A. F. Noels,, J. Delarge,, L. T. Chizhevsky,, T. V. Zinevich,, I. V. Pisareva,, and V. I. Bregadze. 1993. Stereoselective hydrogenation of methacycline to doxycycline catalyzed by rhodium-carborane complexes. Tetrahedron Lett. 34: 1471 1474.
35. Postier, R. G.,, S. L. Green,, S. R. Klein,, E. J. Ellis-Grosse,, and E. Loh. Tigecycline 200 Study Group. Results of a multicenter, randomized, open-label efficacy and safety study of two doses of tigecycline for complicated skin and skin-structure infections in hospitalized patients. Clin. Ther. 26: 704 714.
36. Rebstock, M. C.,, H. M. Crooks,, J. Controulis, Bartz, and Q. R. Bartz. 1949. Chloramphenicol (chloromycetin). IV. Chemical studies. J. Am. Chem. Soc. 71: 2458 2462.
37. Schatz, A.,, and S. A. Waksman. 1944. Effect of streptomycin and other antibiotic substances upon Mycobacterium tuberculosis and related organisms. Proc. Soc. Exp. Biol. Med. 57: 244 248.
38. Stephens, C. R.,, L. H. Conover,, F. A. Hochstein,, P. P. Regna,, F. J. Pilgrim,, K. J. Brunings,, and R. B. Woodward. 1952. Terramycin. VIII. Structure of Aureomycin and Terramycin. J. Am. Chem. Soc. 74: 4976 4977.
39. Stephens, C. R.,, L. H. Conover,, R. Pasternak,, F. A. Hochstein,, W. T. Moreland,, P. P. Regna,, F. J. Pilgrim,, K. J. Brunings,, and R. B. Woodward. 1954. The structure of Aureomycin. J. Am. Chem. Soc. 76: 3568 3575.
40. Stephens, C. R.,, J. J. Beereboom,, H. H. Rennhard,, P. N. Gordon,, K. Murai,, R. K. Blackwood,, and M. Schach von Wittenau. 1963. 6-deoxytetracyclines. IV. Preparation, C-6 stereochemistry, and reactions. J. Am. Chem. Soc. 85: 2643 2652.
41. Sum, P. E.,, V. J. Lee,, R. T. Testa,, J. J. Hlavka,, G. A. Ellestad,, J. D. Bloom,, Y. Gluzman,, and F. P. Tally. 1994. Glycylcyclines. 1. A new generation of potent antibacterial agents through modification of 9-aminotetracyclines. J. Med. Chem. 37: 184 188.
42. Sum, P. E.,, and P. Petersen. 1999. Synthesis and structureactivity relationship of novel glycylcycline derivatives leading to the discovery of GAR-936. Bioorg. Med. Chem. Lett. 9: 1459 1462.
43. Thomas, J. G.,, R. J. Metheny,, J. M. Karakiozis,, J. M. Wetzel,, and R. J. Krout. 1998. Long-term sub-antimicrobial doxycycline (Periostat) as adjunctive management in adult periodontitis: Effects on subgingival bacterial population dynamics. Adv. Den. Res. 12: 32 39.
44. Waller, C. W.,, B. L. Hutchings,, R. W. Broschard,, A. A. Goldman,, W. J. Stein,, C. F. Wolf,, and J. H. Williams. 1952. Degradation of Aureomycin. VII. Aureomycin and anhydroaureomycin. J. Am. Chem. Soc. 74: 4981 4982.
45. Webster, G. F.,, J. J. Leyden,, K. J. McGinley,, and W. P. McArthur. 1982. Suppression of polymorphonuclear leukocyte chemotactic factor production in Propionibacterium acnes by subminimal inhibitory concentrations of tetracycline, ampicillin, minocycline and erythromycin. Antimicrob. Agents Chemother. 21: 770 772.
46. Zambrano, R. T.,, and K. Butler. 1962. Reductive alkylation process. U.S. Patent 3,483,251.
47. Ziv, G.,, and F. G. Sulman. 1971. Analysis of pharmacokinetic properties of nine tetracycline analogs in dairy cows and ewes. Am. J. Vet. Res. 35: 1197 1201. yclines and tigecycline.

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