Total syntheses of vancomycin and eremomycin aglycons

Angewandte Chemie - International Edition

Volumn 37, Issue 19, 1998, Pages 2700-2704

  Evans, David A ^a   Wood, Michael R ^a   Trotter, B Wesley ^a   Richardson, Timothy I ^a   Barrow, James C ^a   Katz, Jeffrey L ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

Antibiotics; Eremomycin; Natural products; Total synthesis; Vancomycin

Indexed keywords

EID: 0032538575     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1521-3773(19981016)37:19<2700::AID-ANIE2700>3.0.CO;2-P     Document Type: Article

References (47)

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2. For a comprehensive discussion of the vancomycin antibiotics see: Glycopeptide Antibiotics (Ed.: R. Nagarajan), Marcel Dekker, New York, 1994.
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8. For reviews on methodology relevant to the synthesis of the vancomycin aglycon structure see: a) D. A. Evans, K. D. DeVries in ref. [2], pp. 63-103; b) A. V. Rama Rao, M. K. Gurjar, K. L. Reddy, A. S. Rao, Chem. Rev. 1995, 95, 2135-2168; c) J. Zhu, Synlett. 1997, 133-144; d) R. M. Williams, J. A. Hendrix, Chem. Rev. 1992, 92, 889-917.
9. For reviews on methodology relevant to the synthesis of the vancomycin aglycon structure see: a) D. A. Evans, K. D. DeVries in ref. [2], pp. 63-103; b) A. V. Rama Rao, M. K. Gurjar, K. L. Reddy, A. S. Rao, Chem. Rev. 1995, 95, 2135-2168; c) J. Zhu, Synlett. 1997, 133-144; d) R. M. Williams, J. A. Hendrix, Chem. Rev. 1992, 92, 889-917.
10. For reviews on methodology relevant to the synthesis of the vancomycin aglycon structure see: a) D. A. Evans, K. D. DeVries in ref. [2], pp. 63-103; b) A. V. Rama Rao, M. K. Gurjar, K. L. Reddy, A. S. Rao, Chem. Rev. 1995, 95, 2135-2168; c) J. Zhu, Synlett. 1997, 133-144; d) R. M. Williams, J. A. Hendrix, Chem. Rev. 1992, 92, 889-917.
11. For reviews on methodology relevant to the synthesis of the vancomycin aglycon structure see: a) D. A. Evans, K. D. DeVries in ref. [2], pp. 63-103; b) A. V. Rama Rao, M. K. Gurjar, K. L. Reddy, A. S. Rao, Chem. Rev. 1995, 95, 2135-2168; c) J. Zhu, Synlett. 1997, 133-144; d) R. M. Williams, J. A. Hendrix, Chem. Rev. 1992, 92, 889-917.
12. p: (4S)-4-(phenylmethyl)-2-oxazolidinone; Tfa: trifluoroacetyl TFA: trifluoroacetic acid; Boc: tert-butoxycarbonyl; NOE: nuclear Overhauser effect; Tf: trifluoromethanesulfonyl; Ms: methanesulfonyl; Bn: benzyl; Piv: pivaloyl; Ddm: 4,4′dimethoxydiphenylmethyl; EDCI · HCl: 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride; HOBt: 1-hydroxybenzotriazole; DMAP: 4-dimethylaminopyridine; DMS: dimethylsulfide; TFAA: trifluoroacetic anhydride; HATU: O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; HOAt: 7-aza-1-hydroxybenzotriazole; LDA: lithium diisopropylamide; dppf: 1,1′-bis(diphenylphosphanyl)ferrocene.
13. a) D. A. Evans, D. A. Evrard, S. D. Rychnovsky, T. Früh, W. G. Wittingham, K. M. DeVries, Tetrahedron Lett. 1992, 33, 1189-1192;
14. b) D. A. Evans, T. C. Britton, J. A. Ellman, R. L. Dorow, J. Am. Chem. Soc. 1990, 112, 4011-4030;
15. c) D. A. Evans, A. E. Weber, J. Am. Chem. Soc. 1987, 109, 7151-7157.
16. a) D. A. Evans, J. A. Ellman, K. M. DeVries, J. Am. Chem. Soc. 1989, 111, 8912-8914;
17. b) D. A. Evans, C. J. Dinsmore, A. M. Ratz,Tetrahedron Lett. 1997, 38, 3189-3192;
18. c) D. A. Evans, P. S. Watson, Tetrahedron Lett. 1996, 37, 3251-3254.
19. a) D. A. Evans, C. J. Dinsmore, D. A. Evrard, K. M. DeVries, J. Am. Chem. Soc. 1993, 115, 6426-6427;
20. b) D. A. Evans, C. J. Dinsmore, Tetrahedron Lett. 1993, 34, 6029-6032.
21. For the synthesis of orienticin C aglycon see: a) D. A. Evans, C. J. Dinsmore, A. M. Ratz, D. A. Evrard, J. C. Barrow, J. Am. Chem. Soc. 1997, 119, 3417-3418; b) D. A. Evans, J. C Barrow, P. S. Watson, A. M. Ratz, C. J. Dinsmore, D. A. Evrard, K. M. DeVries, J. A. Ellman, S. D. Rychnovsky, J. Lacour, J. Am. Chem. Soc. 1997, 119, 3419-3420.
22. For the synthesis of orienticin C aglycon see: a) D. A. Evans, C. J. Dinsmore, A. M. Ratz, D. A. Evrard, J. C. Barrow, J. Am. Chem. Soc. 1997, 119, 3417-3418; b) D. A. Evans, J. C Barrow, P. S. Watson, A. M. Ratz, C. J. Dinsmore, D. A. Evrard, K. M. DeVries, J. A. Ellman, S. D. Rychnovsky, J. Lacour, J. Am. Chem. Soc. 1997, 119, 3419-3420.
23. D. A. Evans, C. J. Dinsmore, P. S. Watson, M. R. Wood, T. I. Richardson, B. W. Trotter, J. L. Katz, Angew. Chem. 1998, 111, 2868-2872; Angew. Chem. Int. Ed. 1998, 37, 2704-2708.
24. D. A. Evans, C. J. Dinsmore, P. S. Watson, M. R. Wood, T. I. Richardson, B. W. Trotter, J. L. Katz, Angew. Chem. 1998, 111, 2868-2872; Angew. Chem. Int. Ed. 1998, 37, 2704-2708.
25. The seven amino acid residues are numbered consecutively starting from the amino terminus. The M(X-Y) nomenclature refers to the macrocycle containing an oxidative cross-link between aryl groups of residues X and Y. Bicyclic moieties will be identified as M(W-Y)(X-Z).
26. Amino acid 4 was derived from (R)-para-hydroxy-phenylglycine.
27. Compound 4b was prepared by the chlorination of 4a: F. D. March, W. B. Farnham, D. J. Sam, B. E. Smart, J. Am. Chem. Soc. 1982, 104, 4680-4682. 4-Fluoro-3-nitrobenzaldehyde (4a) was prepared from 4-fluorobenzaldehyde: F. Michael, D. Noffz, Chem. Ber. 1957, 90, 1586-1589. Dr. S. Rubenstein is acknowledged for the preparation of this material.
28. Compound 4b was prepared by the chlorination of 4a: F. D. March, W. B. Farnham, D. J. Sam, B. E. Smart, J. Am. Chem. Soc. 1982, 104, 4680-4682. 4-Fluoro-3-nitrobenzaldehyde (4a) was prepared from 4-fluorobenzaldehyde: F. Michael, D. Noffz, Chem. Ber. 1957, 90, 1586-1589. Dr. S. Rubenstein is acknowledged for the preparation of this material.
29. Alternate conditions and reagents were plagued by competitive endocyclic oxazolidinone hydrolysis and/or undesired nucleophilic displacement of the fluoride. D. A. Evans, T. C. Britton, J. A. Ellman, Tetrahedron Lett. 1987, 28, 6141-6144.
30. HATU-mediated peptide coupling: L. A. Carpino, A. El-Fahan, C. A. Minor, F Albericio, J. Chem. Soc. Chem. Commun. 1994, 201-203.
31. The removal of the TBS protecting group highlighted the significant reactivity difference between the chloro and des-chloro substrates. Treatment of 13b with TBAF resulted in immediate M(4-6) cyclization with reduced diastereoselection. See also ref. [24].
32. 3) in favor of the unnatural atropisomer. It was further observed that cyclization of substrates in which the meta-phenols of amino acid 4 were both unmasked proceeded with negligible selectivity under a variety of conditions, necessitating the synthesis of a fully differentiated triphenol.
33. 1H NMR, HPLC, and mass spectral data identical to a natural comparison sample (refs. [23] and [27]).
34. We thank Mr. Kevin Campos for determining the X-ray structure of this intermediate.
35. H. J. Shine, S. E. Rhee, J. Am. Chem. Soc. 1986, 108, 1000-1006.
36. This assignment was confirmed by chemical correlation to a minor atropisomer corresponding to 16.
37. S. Cacci, P. G. Ciattini, E. Morera, G. Ortar, Tetrahedron Lett. 1986, 27, 5541-5544.
38. Separation of the undesired M(4-6) atropisomer was most conveniently achieved at this stage; the desired isomer was isolated in 69% yield.
39. The stereochemistry of 20 was confirmed by ROESY analysis (500 MHz).
40. D. L. Boger, R. M. Borzilleri, S. Nukui, R. T. Beresis, J. Org. Chem. 1997, 62, 4721-4736.
41. D. A. Evans, P. H. Carter, C. J. Dinsmore, J. C. Barrow, J. L. Katz, D. W. Kung, Tetrahedron Lett. 1997, 38, 4535-4538.
42. J. Garcia, J. Gonzalez, R. Segura, J. Vilarrasa, Tetrahedron 1984, 40, 3121-3127.
43. A. M. Felix, E. P. Heimer, T. J. Lambros, C. Tzougraki, J. Meienhofer, J. Org. Chem. 1978, 43, 4194-4196.
44. We thank Dr. Bret Huff of Eli Lilly & Company for generous samples of vancomycin · HCl and eremomcyin · HOAc.
45. Vancomycin aglycon was prepared from vancomycin · HCl according to: R. Nagarajan, A. A. Schabel, J. Chem. Soc. Chem. Comm. 1988, 1306-1307; see also F. J. Marshall, J. Med. Chem. 1965, 8, 18-24.
46. Vancomycin aglycon was prepared from vancomycin · HCl according to: R. Nagarajan, A. A. Schabel, J. Chem. Soc. Chem. Comm. 1988, 1306-1307; see also F. J. Marshall, J. Med. Chem. 1965, 8, 18-24.
47. Eremomycin aglycon was prepared from eremomycin · HOAc according to: G. F. Gause, M. G. Brazhnikova, N. N. Lomakina, T. F. Berdnikova, G. B. Fedorova, N. L. Tokareva, V. N. Borisova, G. Y. Batta, J. Antibiotics 1989, 42, 1790-1799.