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Bioscience, Biotechnology, and Biochemistry Volume 67, 2003 - Issue 12
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Original Articles

Synthesis and Activity of Pyrimidinylpropenamide Antibiotics: The Alkyl Analogues of Sparsomycin

Noriyuki NAKAJIMABiotechnology Research Center, Toyama Prefectural UniversityKosugi, Toyama 939-0398, Japan
,
Takeshi ENOMOTOBiotechnology Research Center, Toyama Prefectural UniversityKosugi, Toyama 939-0398, Japan
,
Takehiro WATANABEBiotechnology Research Center, Toyama Prefectural UniversityKosugi, Toyama 939-0398, Japan
,
Nobuyasu MATSUURABiotechnology Research Center, Toyama Prefectural UniversityKosugi, Toyama 939-0398, Japan
&
Makoto UBUKATABiotechnology Research Center, Toyama Prefectural UniversityKosugi, Toyama 939-0398, Japan
Pages 2556-2566 | Received 02 Jun 2003, Accepted 31 Jul 2003, Published online: 22 May 2014

  • 1) Ubukata, M., Morita, T., Kakeya, H., Kobinata, K., Kudo, T., and Osada, H., Sparoxomycins A1 and A2, new inducers of the flat reversion of NRK cells transformed by temperature sensitive rous sarcoma virus, I. Taxonomy of the producing organism, fermentation and biological activity. J. Antibiotics, 49, 1096-1100 (1996).
  • 2) Ubukata, M., Morita, T., Uramoto, M., and Osada, H., Sparoxomycins A1 and A2, new inducers of the flat reversion of NRK cells transformed by temperature sensitive rous sarcoma virus, II. Isolation, physico-chemical properties and structure elucidation. J. Antibiotics, 49, 65-70 (1996).
  • 3) Argoudelis, A. D., and Herr, R. R., Sparsomycin, a new antibiotic II. Isolation and characterization. Antimicrob. Ag. Chemother., 780-786 (1962).
  • 4) Higashide, E., Hasegawa, T., Shibata, M., Mizuno, K., and Akaike, H., Studies on the Streptomycetes. Streptomyces cuspidosporus nov. sp and the antibiotic sparsomycin and tubercidin produced thereby. Ann. Rept. Takeda Res. Lab., 25, 1-14 (1966).
  • 5) Wiley, P. F., and Mackellar, F. A., The structure of sparsomycin. J. Am. Chem. Soc., 92, 417-418 (1970).
  • 6) Ottenheijm, H. C. J., Liskamp, R. M. J., Helquist, P., Lauher, J. W., and Shekhani, M. S., Absolute configuration of sparsomycin. A chiroptical study of sulfoxides. J. Am. Chem. Soc., 103, 1720-1723 (1981).
  • 7) Lazaro, E., Felix, A. S., van den Broek, L. A. G. M., Ottenheijm, H. C. J., and Ballesta, J. P. G., Interaction of the antibiotic sparsomycin with the ribosome. Antimicrob. Ag. Chemother., 10-13 (1991).
  • 8) Lazaro, E., van den Broek, L. A. G. M., Felix, A. S., Ottenheijm, H. C. J., and Ballesta, J. P. G., Biochemical and kinetic characteristics of the interaction of the antibiotic sparsomycin with prokaryotic and eukaryotic ribosomes. Biochemistry, 30, 9642-9648 (1991).
  • 9) Theocharis, D. A., and Coutsogeorgopoulos, C., Mechanism of action of sparsomycin in protein synthesis. Biochemistry, 31, 5861-5868 (1992).
  • 10) Porse, B. T., Kirillov, S. V., Awayz, M. J., Ottenheijm, H. C. J., and Garrett, R. A., Direct crosslinking of the antitumor antibiotic sparsomycin, and its derivatives, to A2602 in the peptidyl transferase center of 23S-like rRNA within ribosome-tRNA complexes. Proc. Natl. Acad. Sci. USA, 96, 9003-9008 (1999).
  • 11) For a review of sparsomycin, see: Ottenheijm, H. C. J., van den Broek, L. A. G. M., Ballesta, J. P. G., and Zylicz, Z., Chemical and biological aspects of sparsomycin, an antibiotic from streptomyces. Progress in Medicinal Chemistry, 23, 220-268 (1986).
  • 12) Ottenheijm, H. C. J., van Nispen, S. P. J. M., and Sinnige, M. J., Synthesis of S-deoxo-(R)-sparsomycin. Tetrahedron Lett., 1899-1902 (1976).
  • 13) Ottenheijm, H. C. J., and Liskamp, R. M. J., Approaches to the antibiotics sparsomycin. An efficient synthesis of the cysteinol mono-oxodithioacetal moiety. Tetrahedron Lett., 2437-2438 (1978).
  • 14) Ottenheijm, H. C. J., Liskamp, R. M. J., and Tijhuis, M. W., Total synthesis of enantiomeric sparsomycin. Tetrahedron Lett., 387-390 (1979).
  • 15) Helquist, P., and Shekhani, M. S., Total synthesis of (R c)-sparsomycin. J. Am. Chem. Soc., 101, 1057-1059 (1979).
  • 16) Ottenheijm, H. C. J., Liskamp, R. M. J., van Nispen, S. P. J., Boots, H. A., and Tijhuis, M. W., Total synthesis of the antibiotic sparsomycin, a modified uracil amino acid monoxodithioacetal. J. Org. Chem., 46, 3273-3283 (1981).
  • 17) Liskamp, R. M. J., Zeegers, H. J. M., and Ottenheijm, H. C. J., Synthesis and ring-opening reactions of functionalized sultines. A new approach to sparsomycin. J. Org. Chem., 46, 5408-5413 (1981).
  • 18) Wang, D.-R. H., Helquist, P., and Shekhani, M. S., Total synthesis of sparsomycin. Approaches using cysteine and serine inversion. J. Org. Chem., 50, 1264-1271 (1985).
  • 19) Parry, R. J., Li, Y., and Gomez, E. E., Biosynthesis of the antitumor antibiotic sparsomycin. J. Am. Chem. Soc., 114, 5946-5959 (1992).
  • 20) Parry, R. J., Hoyt, J. C., and Li, Y., The biosynthesis of sparsomycin. Further investigations of the biosynthesis of the uracil acrylic acid moiety. Tetrahedron Lett., 7497-7500 (1994).
  • 21) Lin, C.-C. L., and Dubois, R. J., Pyrimidinylpropenamides as antitumor agents. Analogues of the antibiotic sparsomycin. J. Med. Chem., 20, 337-341 (1977).
  • 22) Lee, C. K., and Vince, R., Effect of sparsomycin analogues on the puromycin-peptidyl transferase reaction on ribosomes. J. Med. Chem., 21, 176-179 (1978).
  • 23) Zemlicka, J., and Bhuta, A., Sparsophenicol: A new synthetic hybrid antibiotic inhibiting ribosomal peptide synthesis. J. Med. Chem., 25, 1123-1125 (1982).
  • 24) Duke, A. A., and Boots, M. R., Synthesis and biological evaluation of sparsomycin analogues. J. Med. Chem., 26, 1556-1561 (1983).
  • 25) Liskamp, R. M. J., Colstee, J. H., Ottenheijm, H. C. J., Lelieveld, P., and Akkermann, W., Structure-activity relationships of sparsomycin and its analogues. Octylsparsomycin: The first analogue more active than sparsomycin. J. Med. Chem., 27, 301-306 (1984).
  • 26) Van den Broek, L. A. G. M., Liskamp, R. M. J., Colstee, J. H., Leilieveld, P., Remacha, M., Vazquez, D., Ballesta, J. P. G., and Ottenheijm, H. C. J., Structure-activity relationships of sparsomycin and its analogues. Inhibition of peptide bond formation in cell-free systems and L1210 and bacterial cell. J. Med. Chem., 30, 325-333 (1987).
  • 27) Van den Broek, L. A. G. M., Lazaro, E., Zylicz, Z., Fennis, P. J., Missler, F. A. N., Leilieveld, P., Garzotto, M., Wanger, D. J. F., Ballesta, J. P. G., and Ottenheijm, H. C. J., Lipophilic analogues of sparsomycin as strong inhibitors of protein synthesis and tumor growth: Structure-activity relationship study. J. Med. Chem., 32, 2002-2015 (1989).
  • 28) Preliminary communication, see: Nakajima, N., Enomoto, T., Matsuura, N., and Ubukata, M., Synthesis and morphological reversion activity on src ts-NRK cells of pyrimidinylpropenamide antibiotics, sparsomycin, sparoxomycins A1, A2, and their analogues. Bioorganic & Medicinal Chemistry Letters, 8, 3331-3334 (1998).
  • 29) Uehara, Y., Hori, M., Takeuchi, T., and Umezawa, H., Screening of agents which convert transformed morphology of rous sarcoma virus-infected rat kidney cells to normal morphology: identification of an active agent as herbimycin and its inhibition of intracellular srckinase. Jap. J. Cancer Res. (Gann), 76, 672 (1985).
  • 30) Kagan, H. B., “Catalytic Asymmetric Synthesis”, ed. Ojima, I., VCH, New York, pp. 203-226 (1993).
  • 31) Pitchen, P., and Kagan, H. B., An efficient asymmetric oxidation of sulfides to sulfoxides. Tetrahedron Lett., 25, 1049-1052 (1984).
  • 32) Pitchen, P., Dunach, E., Deshmukh, M. N., and Kagan, H. B., An efficient asymmetric oxidation of sulfides to sulfoxides. J. Am. Chem. Soc., 106, 8188 (1984).
  • 33) Zhao, S. H., Samuel, O., and Kagan, H. B., Asymmetric oxidation of sulfides mediated by chiral titanium complexes: mechanistic and synthetic aspects. Tetrahedron, 43, 5135-5144 (1987).
  • 34) Komatsu, N., Nishibayashi, Y., Sugita, T., and Uemura, A., Catalytic asymmetric oxidation of sulfides to sulfoxides using R-(+)-binaphthol. Tetrahedron Lett., 33, 5391-5394 (1992).
  • 35) Komatsu, N., Hashizume, M., Sugita, T., and Uemura, A., Catalytic asymmetric oxidation of sulfides to sulfoxides with tert-butyl hydroperoxide using binaphthol as a chiral auxiliary. J. Org. Chem., 58, 4529-4533 (1993).
  • 36) ScSs: S configuration at the carbon and sulfur atoms. ScRs: S configuration at the carbon and R configuration at the sulfur atoms.
  • 37) Reaction for 30 min at 0°C. The yields obtained after 60 min at 0°C are as follows: 17a (20%), 17b (25%), 16 (41%).
  • 38) This compound was prepared from commercially available 5-hydroxymethyl-6-methyluracil (Sigma) by Dubois procedure.22)
  • 39) Carpino, L. A., 1-Hydroxy-7-azabenzotriazole. An efficient peptide coupling additive. J. Am. Chem. Soc., 115, 4397-4398 (1993).
  • 40) ID50 values of HeLa S3 colony formation inhibition (μM) were as follows: 19 (13.4), 20 (3.1), 21 (1.6), 3 (0.8), 4 (0.7), 5 (0.6), 6 (0.8), 7 (0.6).

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