Synlett 2015; 26(16): 2199-2215
DOI: 10.1055/s-0034-1381047
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© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of Desmethyl Macrolide Antibiotics

Rodrigo B. Andrade*
  • Temple University, Department of Chemistry, Philadelphia, PA 19122, USA   Email: randrade@temple.edu
Further Information

Publication History

Received: 13 April 2015

Accepted after revision: 09 June 2015

Publication Date:
03 September 2015 (eFirst)

Dedicated to the memory of Dr. Tapas Paul (1976–2012). ‘Chemistry creates its object.’ – Marcelin Berthelot (1860)

Abstract

Macrolide antibiotics occupy a special place in the history of organic chemistry and medicine. This account chronicles the evolution of our approach that ultimately led to the successful total syntheses of four desmethyl (i.e., Me → H) analogues of telithromycin, a semisynthetic derivative of the flagship macrolide antibiotic, erythromycin.

1 Introduction

2 Project Rationale and Retrosynthetic Analysis

3 Lessons Learned from the Total Synthesis of 4,8,10-Tridesmethyl Telithromycin

4 Total Synthesis of 4,10-Didesmethyl Telithromycin

5 Total Synthesis of 4,8-Didesmethyl Telithromycin

6 Total Synthesis of 4-Desmethyl Telithromycin

7 Biological Evaluation of Desmethyl Telithromycin Analogues

8 Concluding Remarks

 
  • References

  • 1 Wagh B, Paul T, DeBrosse C, Klepacki D, Small MC, MacKerell AD, Andrade RB. ACS Med. Chem. Lett. 2013; 4: 1114
  • 2 Walsh C. Nat. Rev. Microbiol. 2003; 1: 65
  • 3 Bush K, Courvalin P, Dantas G, Davies J, Eisenstein B, Huovinen P, Jacoby GA, Kishony R, Kreiswirth BN, Kutter E, Lerner SA, Levy S, Lewis K, Lomovskaya O, Miller JH, Mobashery S, Piddock LJ. V, Projan S, Thomas CM, Tomasz A, Tulkens PM, Walsh TR, Watson JD, Witkowski J, Witte W, Wright G, Yeh P, Zgurskaya HI. Nat. Rev. Microbiol. 2011; 9: 894
  • 4 Xu Z.-Q, Flavin M, Eiznhamer D In Antibiotic Discovery and Development . Dougherty TJ, Pucci MJ. Springer; New York; 2012: 181
  • 5 Bryskier A. Clin. Microbiol. Infect. 2000; 6: 661
  • 6 Pal S. Tetrahedron 2006; 62: 3171
  • 7 Nobelprize.org - The Official Web Site of the Nobel Prize. http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2009/ (accessed July 23, 2015).
  • 8 Tu D, Blaha G, Moore PB, Steitz TA. Cell 2005; 121: 257
  • 9 Jacobsen JR, Hutchinson CR, Cane DE, Khosla C. Science 1997; 277: 367
  • 10 Petkovic H, Lill RE, Sheridan RM, Wilkinson B, McCormick EL, McArthur HA. I, Staunton J, Leadlay PF, Kendrew SG. J. Antibiot. 2003; 56: 543
  • 11 Velvadapu V, Paul T, Wagh B, Klepacki D, Guvench O, MacKerell A, Andrade RB. ACS Med. Chem. Lett. 2011; 2: 68
  • 12 Velvadapu V, Paul T, Wagh B, Glassford I, DeBrosse C, Andrade RB. J. Org. Chem. 2011; 76: 7516
  • 13 Velvadapu V, Glassford I, Lee M, Paul T, DeBrosse C, Klepacki D, Small MC, MacKerell AD. Jr, Andrade RB. ACS Med. Chem. Lett. 2012; 3: 211
  • 14 Wagh B, Paul T, Glassford I, DeBrosse C, Klepacki D, Small MC, MacKerell AD. Jr, Andrade RB. ACS Med. Chem. Lett. 2012; 3: 1013
  • 15 Glassford I, Lee M, Wagh B, Velyadapu V, Paul T, Sandelin G, DeBrosse C, Klepacki D, Small MC, MacKerell AD, Andrade RB. ACS Med. Chem. Lett. 2014; 5: 1021
  • 16 Woodward RB, Logusch E, Nambiar KP, Sakan K, Ward DE, Auyeung BW, Balaram P, Browne LJ, Card PJ, Chen CH, Chenevert RB, Fliri A, Frobel K, Gais HJ, Garratt DG, Hayakawa K, Heggie W, Hesson DP, Hoppe D, Hoppe I, Hyatt JA, Ikeda D, Jacobi PA, Kim KS, Kobuke Y, Kojima K, Krowicki K, Lee VJ, Leutert T, Malchenko S, Martens J, Matthews RS, Ong BS, Press JB, Rajanbabu TV, Rousseau G, Sauter HM, Suzuki M, Tatsuta K, Tolbert LM, Truesdale EA, Uchida I, Ueda Y, Uyehara T, Vasella AT, Vladuchick WC, Wade PA, Williams RM, Wong HN. C. J. Am. Chem. Soc. 1981; 103: 3215
  • 17 Denis A, Agouridas C, Auger JM, Benedetti Y, Bonnefoy A, Bretin F, Chantot JF, Dussarat A, Fromentin C, D’Ambrieres SG, Lachaud S, Laurin P, Le Martret O, Loyau V, Tessot N, Pejac JM, Perron S. Bioorg. Med. Chem. Lett. 1999; 9: 3075
  • 18 Baker WR, Clark JD, Stephens RL, Kim KH. J. Org. Chem. 1988; 53: 2340
  • 19 Inanaga J, Hirata K, Saeki H, Katsuki T, Yamaguchi M. Bull. Chem. Soc. Jpn. 1979; 52: 1989
  • 20 Evans DA, Bartroli J, Shih TL. J. Am. Chem. Soc. 1981; 103: 2127
  • 21 Jin H, Uenishi J, Christ WJ, Kishi Y. J. Am. Chem. Soc. 1986; 108: 5644
  • 22 Takai K, Kimura K, Kuroda T, Hiyama T, Nozaki H. Tetrahedron Lett. 1983; 24: 5281
  • 23 Trnka TM, Grubbs RH. Acc. Chem. Res. 2001; 34: 18
  • 24 Kolb HC, Vannieuwenhze MS, Sharpless KB. Chem. Rev. 1994; 94: 2483
  • 25 Johnson WS, Werthema L, Bartlett WR, Brocksom TJ, Li TT, Faulkner DJ, Petersen MR. J. Am. Chem. Soc. 1970; 92: 741
  • 26 Martin SF, Lee WC, Pacofsky GJ, Gist RP, Mulhern TA. J. Am. Chem. Soc. 1994; 116: 4674
  • 27 Mancuso AJ, Swern D. Synthesis 1981; 165
  • 28 Corey EJ, Fuchs PL. Tetrahedron Lett. 1972; 13: 3769
  • 29 Yadav JS, Pratap TV, Rajender V. J. Org. Chem. 2007; 72: 5882
  • 30 Rucker C. Chem. Rev. 1995; 95: 1009
  • 31 Venkatraman L, Salomon CE, Sherman DH, Fecik RA. J. Org. Chem. 2006; 71: 9853
  • 32 Dess DB, Martin JC. J. Org. Chem. 1983; 48: 4155
  • 33 Evans DA, Ratz AM, Huff BE, Sheppard GS. Tetrahedron Lett. 1994; 35: 7171
  • 34 Nelson TD, Crouch RD. Synthesis 1996; 1031
  • 35 Xuan R, Oh H.-S, Lee Y, Kang H.-Y. J. Org. Chem. 2008; 73: 1456
  • 36 Scholl M, Ding S, Lee CW, Grubbs RH. Org. Lett. 1999; 1: 953
  • 37 Hergenrother PJ, Hodgson A, Judd AS, Lee WC, Martin SF. Angew. Chem. Int. Ed. 2003; 42: 3278
  • 38 Toshima K, Nozaki Y, Mukaiyama S, Tamai T, Nakata M, Tatsuta K, Kinoshita M. J. Am. Chem. Soc. 1995; 117: 3717
  • 39 Dauben WG, Fonken GJ, Noyce DS. J. Am. Chem. Soc. 1956; 78: 2579
  • 40 Scheidt KA, Chen H, Follows BC, Chemler SR, Coffey DS, Roush WR. J. Org. Chem. 1998; 63: 6436
  • 41 Corey EJ, Kim CU. J. Am. Chem. Soc. 1972; 94: 7586
  • 42 Zimmerman HE. Acc. Chem. Res. 1987; 20: 263
  • 43 Breton P, Hergenrother PJ, Hida T, Hodgson A, Judd AS, Kraynack E, Kym PR, Lee W.-C, Loft MS, Yamashita M, Martin SF. Tetrahedron 2007; 63: 5709
  • 44 Zhang HX, Guibe F, Balavoine G. J. Org. Chem. 1990; 55: 1857
  • 45 Agouridas C, Denis A, Auger JM, Benedetti Y, Bonnefoy A, Bretin F, Chantot JF, Dussarat A, Fromentin C, D’Ambrieres SG, Lachaud S, Laurin P, Le Martret O, Loyau V, Tessot N. J. Med. Chem. 1998; 41: 4080
  • 46 Oikawa Y, Tanaka T, Horita K, Yonemitsu O. Tetrahedron Lett. 1984; 25: 5397
  • 47 Parenty A, Moreau X, Campagne JM. Chem. Rev. 2006; 106: 911
  • 48 Choi HW, Demeke D, Kang FA, Kishi Y, Nakajima K, Nowak P, Wan ZK, Xie CY. Pure Appl. Chem. 2003; 75: 1
  • 49 Small MC, Lopes P, Andrade RB, MacKerell AD. PLoS Comput. Biol. 2013; 9: e1003113
  • 50 Schlunzen F, Zarivach R, Harms J, Bashan A, Tocilj A, Albrecht R, Yonath A, Franceschi F. Nature 2001; 413: 814
  • 51 Berisio R, Harms J, Schluenzen F, Zarivach R, Hansen HA. S, Fucini P, Yonath A. J. Bacteriol. 2003; 185: 4276
  • 52 Dunkle JA, Xiong L, Mankin AS, Cate JH. D. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 17152
  • 53 Wright PM, Seiple IB, Myers AG. Angew. Chem. Int. Ed. 2014; 53: 8840