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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

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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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Discovery and Industrialization of Therapeutically Important Tetracyclines
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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
/content/10.1128/9781555817572.chap3.fig3-1
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.

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).

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Image of Figure 2
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.

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Image of Figure 3
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).

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Image of Figure 4
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.

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10.1128/9781555817572/fig3-5.gif
Image of Figure 5
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).

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Image of Figure 6
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.

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10.1128/9781555817572/fig3-7.gif
Image of Figure 7
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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