Chimeric azalides with functionalized western portions

Heterocycles

Volumn 43, Issue 11, 1996, Pages 2325-2332

  Waddell, Sherman T ^a   Eckert, Jeffrey M ^a   Blizzard, Timothy A ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 2742572867     PISSN: 03855414     EISSN: None     Source Type: Journal    
DOI: 10.3987/com-96-7569     Document Type: Article

References (15)

1. (a) The term '"azalide", originally coined by Pfizer, refers here to ring nitrogen containing derivatives of erythromycin A.
2. (b) Compound (1) , also called azithromycin and marketed by Pfizer as Zithromax™, is described in S. Djokic, G. Kobrehel, G. Lazarevski, N. Loppotar, Z. Tamburasev, B. Kamenar, A. Nagl, and I. Vickovic, J. Chem. Soc., Perkin Trans.I,1986, 1881
3. and G. Bright, A. Nagel, J. Bordner, K. Desai, J. Dibrino, J. Nowakowska, L. Vincent, R. Watrous, F. Sciavolino, A. English, J. Retsema, M. Anderson, L. Brennan, R. Borovoy, C. Cimochowski, J. Faiella, A. Girard, D. Girard, C. Herbert, M. Manousos, and R. Mason, J. Antibiotics, 1988, 41, 1029.
4. (c) Compound (2) is described in R. Wilkening, R. Ratcliffe, G. Doss, K. Bartizal, A. Graham, and C. Herbert, Bioorg. and Med. Chem. Lett., 1993, 6, 1287.
5. Chimeric describes the state of being assembled from disparate pieces, and here refers to an azalide with an eastern half derived from erythromycin and a western half derived from an exogenous source.
6. The "chimeric annelation sequence" has been previously described in S. Waddell and T. Blizzard, Tetrahedron Lett., 1993, 34, 5385.
7. The sidechain for compound (7) was prepared by treatment of the commercial 5-(hydroxymethyl)furfural with TBDMS-Cl. The sidechain for compound (8) was prepared by selective monosilylation of 1,2-benzenedimethanol (see P. McDougal, J. Rico, Y. Oh,and B. Condon, J. Org. Chem. , 1986, 51, 3389) followed by oxidation with PDC.
8. 2), protection of the liberated hydroxy with TBDMS-C1, and conversion of the dithioacetal to the aldehyde (Mel, collidine, acetone.)
9. For photoreductive cleavage of benzenesulfonamides see T. Hamada, A. Nishida, and O. Yonemitsu, J. Am. Chem. Soc., 1986, 108, 140.
10. The synthesis of 2-(OBn)-glyceraldehyde (sidechain for compounds (12) and (13)) is described in V. Jager and V. Wehner, Ang. Chem., Int. Ed. Eng., 1989, 28, 469.
11. a) M. Hikota, Y. Sakurai, K. Horita, and O. Yonemitsu, Tetrahedron Lett., 1990, 31, 6367.
12. b) J. Inanaga, K. Hirata, H. Saeki, and T. Katsuki, Bull. Chem. Soc. Jap., 1979, 52, 1989.
13. The sidechain for compound (9) was prepared from commercial optically pure (R)-2-methylglycidol by ring opening with azide (see K. B. Sharpless and C. Behrens, J. Org. Chem., 1985, 50, 5696),
14. 3/pyridine with DMSO (see J. Parikh and W. Doering, J. Am. Chem. Soc., 1967, 89, 5505.)
15. 3 benzene, 65°C) was substituted for reaction with TBDMS-Cl.