Discovery and Industrialization of Therapeutically Important Tetracyclines

Mark L. Nelson; Steven J. Projan

doi:10.1128/9781555817572.ch3

Chapter 3 : Discovery and Industrialization of Therapeutically Important Tetracyclines

Authors: Mark L. Nelson¹, Steven J. Projan²

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Affiliations: 1: Paratek Pharmaceuticals, 75 Kneeland Street, Boston, MA 02111; 2: Wyeth Research, 200 Cambridge Park Drive 5001C, Cambridge, MA 02140

Content Type: Monograph

Publication Year: 2005

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555817572

Chapter DOI: 10.1128/9781555817572.ch3

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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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Discovery and Industrialization of Therapeutically Important Tetracyclines

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Figure 1

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

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Figure 1

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

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Figure 2

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

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Figure 2

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

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Figure 3

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

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Figure 3

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

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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).

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Figure 4

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Figure 5

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

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Figure 5

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

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Figure 6

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

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Figure 6

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

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Figure 7

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

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Figure 7

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

References

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