A platform for the discovery of new macrolide antibiotics

Nature

Volumn 533, Issue , 2016, Pages 338-345

  Seiple, Ian B ^a   Zhang, Ziyang ^a   Jakubec, Pavol ^a   Langlois Mercier, Audrey ^a,b,j   Wright, Peter M ^a   Hog, Daniel T ^a,c   Yabu, Kazuo ^a   Allu, Senkara Rao ^a,d   Fukuzaki, Takehiro ^a   Carlsen, Peter N ^a,e   Kitamura, Yoshiaki ^a   Zhou, Xiang ^a,f   Condakes, Matthew L ^a   Szczypiński, Filip T ^a,g   Green, William D ^a,h   Myers, Andrew G ^a,i  

^a HARVARD UNIVERSITY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c MCKINSEY AND COMPANY   (United States)

^d BAYER PHARMA AG   (Germany)

^e DAIICHI SANKYO CO   (Japan)

^f GIFU UNIVERSITY   (Japan)

^g UNIVERSITY OF CALIFORNIA   (United States)

^h UNIVERSITY OF CAMBRIDGE   (United Kingdom)

ⁱ TRINITY COLLEGE   (United Kingdom)

^j NOVARTIS PHARMA AG   (Switzerland)

more..

Author keywords

[No Author keywords available]

Indexed keywords

AZITHROMYCIN; CETHROMYCIN; CLARITHROMYCIN; ERYTHROMYCIN; MACROLIDE; SOLITHROMYCIN; TELITHROMYCIN; AMINOSUGAR; ANTIINFECTIVE AGENT; KETOLIDE; MOLECULAR LIBRARY; TRIAZOLE DERIVATIVE;

ANTIBIOTIC RESISTANCE; ANTIBIOTICS; BACTERIUM; DISEASE TREATMENT; DRUG DEVELOPMENT; FERMENTATION; INFECTIOUS DISEASE;

ANTIMICROBIAL ACTIVITY; ARTICLE; BACTERIAL STRAIN; BACTERIAL VIRULENCE; DRUG MANUFACTURE; DRUG SCREENING; DRUG SYNTHESIS; DRUG USE; NONHUMAN; PRIORITY JOURNAL; BACTERIUM; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; HUMAN; MICROBIAL SENSITIVITY TEST; MOLECULAR LIBRARY; PROCEDURES; SYNTHESIS;

BACTERIA (MICROORGANISMS);

AMINO SUGARS; ANTI-BACTERIAL AGENTS; BACTERIA; DRUG DISCOVERY; HUMANS; KETOLIDES; MACROLIDES; MICROBIAL SENSITIVITY TESTS; MOLECULAR STRUCTURE; SMALL MOLECULE LIBRARIES; TRIAZOLES;

EID: 84970948129     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature17967     Document Type: Article

References (50)

1. Walsh, C. Antibiotics: Actions, Origins, Resistance (American Society for Microbiology Press, 2003).
2. Fischbach, M. A. & Walsh, C. T. Antibiotics for emerging pathogens. Science 325, 1089-1093 (2009).
3. Wright, P. M., Seiple, I. B. & Myers, A. G. The evolving role of chemical synthesis in antibacterial drug discovery. Angew. Chem. Int. Ed. 53, 8840-8869 (2014).
4. Mcguire, J. M. et al. Ilotycin, a new antibiotic. Antibiot. Chemother. 2, 281-283 (1952).
5. Woodward, R. B. et al. Asymmetric total synthesis of erythromycin. 3 Total synthesis of erythromycin. J. Am. Chem. Soc. 103, 3215-3217 (1981).
6. Martin, S. F., Hida, T., Kym, P. R., Loft, M. & Hodgson, A. The asymmetric synthesis of erythromycin B. J. Am. Chem. Soc. 119, 3193-3194 (1997).
7. Kim, H. C. & Kang, S. H. Total synthesis of azithromycin. Angew. Chem. Int. Ed. 48, 1827-1829 (2009).
8. Andrade, R. B. Total synthesis of desmethyl macrolide antibiotics. Synlett 26, 2199-2215 (2015).
9. Khosla, C. Harnessing the biosynthetic potential of modular polyketide synthases. Chem. Rev. 97, 2577-2590 (1997).
10. Cane, D. E., Walsh, C. T. & Khosla, C. Harnessing the biosynthetic code: combinations, permutations, and mutations. Science 282, 63-68 (1998).
11. Marsden, A. F. A. et al. Engineering broader specificity into an antibioticproducing polyketide synthase. Science 279, 199-202 (1998).
12. Park, S. R. et al. Genetic engineering of macrolide biosynthesis: past advances, current state, and future prospects. Appl. Microbiol. Biotechnol. 85, 1227-1239 (2010).
13. Kurath, P., Jones, P. H., Egan, R. S. & Perun, T. J. Acid degradation of erythromycin A and erythromycin B. Experientia 27, 362 (1971).
14. Bright, G. M. et al. Synthesis, in vitro and in vivo activity of novel 9-deoxo-9aaza-9a-homoerythromycin A derivatives-A new class of macrolide antibiotics, the azalides. J. Antibiot. (Tokyo) 41, 1029-1047 (1988).
15. Morimoto, S., Takahashi, Y., Watanabe, Y. & Omura, S. Chemical modification of erythromycins. 1. Synthesis and antibacterial activity of 6-O-methylerythromycins-A. J. Antibiot. (Tokyo) 37, 187-189 (1984).
16. Fernandes, P. B. Methods for treating gastrointestinal diseases. WO patent 2010/048599 (2010).
17. Putnam, S. D., Castanheira, M., Moet, G. J., Farrell, D. J. & Jones, R. N. CEM-101, a novel fluoroketolide: Antimicrobial activity against a diverse collection of Gram-positive and Gram-negative bacteria. Diagn. Microbiol. Infect. Dis. 66, 393-401 (2010).
18. Leclercq, R. Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications. Clin. Infect. Dis. 34, 482-492 (2002).
19. Gaynor, M. & Mankin, A. S. Macrolide antibiotics: binding site, mechanism of action, resistance. Curr. Top. Med. Chem. 3, 949-961 (2003).
20. Subramanian, S. L., Ramu, H. & Mankin, A. S. in Antibiotic Discovery and Development (eds Dougherty, T. J. & Pucci, M. J.) 455-484 (Springer, 2012).
21. Bryskier, A. Ketolides-Telithromycin, an example of a new class of antibacterial agents. Clin. Microbiol. Infect. 6, 661-669 (2000).
22. Zhanel, G. G. et al. The ketolides: A critical review. Drugs 62, 1771-1804 (2002).
23. Retsema, J. et al. Spectrum and mode of action of azithromycin (CP-62, 993), a new 15-membered-ring macrolide with improved potency against Gram-negative organisms. Antimicrob. Agents Chemother. 31, 1939-1947 (1987).
24. Girard, A. E. et al. Pharmacokinetic and in vivo studies with azithromycin (CP-62, 993), a new macrolide with an extended half-life and excellent tissue distribution. Antimicrob. Agents Chemother. 31, 1948-1954 (1987).
25. Denis, A. & Agouridas, C. Synthesis of 6-O-methyl-Azithromycin and its ketolide analog via Beckmann rearrangement of 9(E)-6-O-methyl-erythromycin oxime. Bioorg. Med. Chem. Lett. 8, 2427-2432 (1998).
26. Boeckman, R. K., Jr & Pruitt, J. R. A new, highly efficient, selective methodology for formation of medium-ring and macrocyclic lactones via intramolecular ketene trapping: An application to a convergent synthesis of (-)-kromycin. J. Am. Chem. Soc. 111, 8286-8288 (1989).
27. Boeckman, R. K. Jr & Perni, R. B. Studies directed toward the synthesis of naturally occurring acyltetramic acids. 2. Preparation of the macrocyclic subunit of ikarugamycin. J. Org. Chem. 51, 5486-5489 (1986).
28. Woodward, R. B. et al. Asymmetric total synthesis of erythromycin. 2. Synthesis of an erythronolide A lactone system. J. Am. Chem. Soc. 103, 3213-3215 (1981).
29. Rostovtsev, V. V., Green, L. G., Fokin, V. V. & Sharpless, K. B. A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. Angew. Chem. Int. Ed. 41, 2596-2599 (2002).
30. Berisio, R. et al. Structural insight into the antibiotic action of telithromycin against resistant mutants. J. Bacteriol. 185, 4276-4279 (2003).
31. Tu, D., Blaha, G., Moore, P. B. & Steitz, T. A. Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell 121, 257-270 (2005).
32. Llano-Sotelo, B. et al. Binding and action of CEM-101, a new fluoroketolide antibiotic that inhibits protein synthesis. Antimicrob. Agents Chemother. 54, 4961-4970 (2010).
33. Bulkley, D., Innis, C. A., Blaha, G. & Steitz, T. A. Revisiting the structures of several antibiotics bound to the bacterial ribosome. Proc. Natl Acad. Sci. USA 107, 17158-17163 (2010).
34. Eyal, Z. et al. Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus. Proc. Natl Acad. Sci. USA 112, E5805-E5814 (2015).
35. Seiple, I. B., Hog, D. T. & Myers, A. G. Practical protocols for the preparation of highly enantioenriched silyl ethers of (R)-3-hydroxypentan-2-one, building blocks for the synthesis of macrolide antibiotics. Synlett 27, 57-60 (2016).
36. Seiple, I. B., Mercer, J. A. M., Sussman, R. J., Zhang, Z. & Myers, A. G. Stereocontrolled synthesis of syn-β-hydroxy-α-Amino acids by direct aldolization of pseudoephenamine glycinamide. Angew. Chem. Int. Ed. 53, 4642-4647 (2014).
37. Mikami, K., Kawakami, Y., Akiyama, K. & Aikawa, K. Enantioselective catalysis of ketoester-ene reaction of silyl enol ether to construct quaternary carbons by chiral dicationic palladium(II) complexes. J. Am. Chem. Soc. 129, 12950-12951 (2007).
38. Mukaiyama, T., Narasaka, K. & Banno, K. New aldol type reaction. Chem. Lett. 2, 1011-1014 (1973).
39. Zhang, Z., Kitamura, Y. & Myers, A. G. An efficient directed Claisen reaction allows for rapid construction of 5, 6-disubstituted 1, 3-dioxin-4-ones. Synthesis 47, 2709-2712 (2015).
40. Hauske, J. R. & Schulte, G. R. Desosamino derivatives of macrolides as immunosuppressants and antifungal agents. WO patent 1993018042 (1993).
41. Zhang, Z., Fukuzaki, T. & Myers, A. G. Synthesis of D-desosamine and analogs by rapid assembly of 3-Amino sugars. Angew. Chem. Int. Ed. 55, 523-527 (2016).
42. Leyes, A. E. & Poulter, C. D. Synthesis of (R)-[2-2H]isopentenyl diphosphate and determination of its enantiopurity by 2H NMR spectroscopy in a lyotropic medium. Org. Lett. 1, 1067-1070 (1999).
43. Tan, Z. & Negishi, E.-i. An efficient and general method for the synthesis of α , ω-difunctional reduced polypropionates by Zr-catalyzed asymmetric carboalumination: synthesis of the scyphostatin side chain. Angew. Chem. Int. Ed. 43, 2911-2914 (2004).
44. Santaniello, E., Ferraboschi, P. & Grisenti, P. An efficient chemo-enzymatic approach to the enantioselective synthesis of 2-methyl-1, 3-propanediol derivatives. Tetrahedr. Lett. 31, 5657-5660 (1990).
45. Thompson, A. S., Corley, E. G., Huntington, M. F. & Grabowski, E. J. J. Use of an ephedrine alkoxide to mediate enantioselective addition of an acetylide to a prochiral ketone: Asymmetric synthesis of the reverse transcriptase inhibitor L-743, 726. Tetrahedr. Lett. 36, 8937-8940 (1995).
46. Sato, F., Ishikawa, H., Watanabe, H., Miyake, T. & Sato, M. Specific hydromagnesiation of prop-2-ynylic alcohols. A simple and specific route to terpenoids. J. Chem. Soc. Chem. Commun. 718-720 (1981).
47. Ashley, G. et al. Ketolide antibacterials. US patent 6, 590, 083 (2003).
48. Antibiotic Resistance Threats in the United States, 2013. http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-Threats-2013-508.pdf (CDC, US Dept Health and Human Services, 2013).
49. Charest, M. G., Lerner, C. D., Brubaker, J. D., Siegel, D. R. & Myers, A. G. A convergent enantioselective route to structurally diverse 6-deoxytetracycline antibiotics. Science 308, 395-398 (2005).
50. Liu, F. & Myers, A. G. Development of a platform for the discovery and practical synthesis of new tetracycline antibiotics. Curr. Opin. Chem. Biol. 32, 48-57 (2016).