Studies on the synthesis of furo[3,2-d]pyrimidine c-nucleosides: New inosine analogues with antiprotozoan activity

Nucleosides and Nucleotides

Volumn 9, Issue 8, 1990, Pages 1021-1043

  Bhattacharya, Birendra K ^a   Otter, Brian A ^b   Berens, Randolph L ^c   Klein, Robert S ^b  

^a MONTEFIORE MEDICAL CENTER   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^c UNIVERSITY OF COLORADO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE; ANTIPROTOZOAL AGENT; INOSINE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; LEISHMANIA DONOVANI; NONHUMAN; TRYPANOSOMA GAMBIENSE;

EID: 0025697219     PISSN: 07328311     EISSN: None     Source Type: Journal    
DOI: 10.1080/07328319008046060     Document Type: Article

References (29)

1. Support of this investigation by funds from the American Cancer Society (grant CH-305) and from the Department of Health and Human Services (grants CA-24634 and AI-121909 [to RLB]) is gratefully acknowledged. Additional support from the Cancer Center Support Grants CA-13330 (for work carried out at Montefiore Medical Center) and CA-08748 (for work carried out at Memorial Sloan-Kettering Cancer Center) is also acknowledged.
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5. J. J. Marr, R. L. Berens, N. K. Cohn, D. J. Nelson, and R. S. Klein, Antimicrob. Agents Chemother., 25, 292 (1984), and references therein. b) J. D. Berman, P. Rainey and D. V. Santi, J. Exp. Med., 158, 252 (1983).
6. M.-I. Lim, R. S. Klein and J. J. Fox, Tetrahedron Lett., 21 (1980). b) M.-I. Lim, W-Y. Ren, B. A. Otter and R. S. Klein, Org. J. Chem., 48, 780 (1983).
7. C. J. Bacchi, R. L. Berens, H. C. Nathan, R. S. Klein, I. A. Elegbe, K. V. B. Rao, P. P. McCann, and J. J. Marr, Antimicrob. Agents Chemother., 31, 1406 (1987). b) S. W. LaFon, D. J. Nelson, R. L. Berens and J. J. Marr, J. Biol. Chem., 260, 9660 (1985).
8. J. W. Smith, M. S. Bartlett, S. F. Queener, M. M. Durkin, M. A. Jay, M. T. Hull, R. S. Klein, and J. J. Marr, Diagn. Microbiol. Infect. Dis., 7, 113 (1987).
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10. B. K. Bhattacharya, M-I. Lim, B. A. Otter and R. S. Klein, Tetrahedron Lett., 27 815 (1986). b) A preliminary account of portions of this study has appeared. B. K. Bhattacharya, M-I. Lim, B. A. Otter and R. S. Klein, 191st ACS National Meeting, New York, NY, 1986 abstr. CARB 005.
11. S. De Bernardo and M. Weigele, J. Org. Chem., 42, 109 (1977).
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13. M. Mikolajczyk and F. Luczak, Chem. and Ind., 76 (1972); idem. Synthesis 491 (1974).
14. L. B. Townsend in “Synthetic Procedures in Nucleic Acid Chemistry,11 Vol 2. W. W. Zorbach and R. S. Tipson, eds., Wiley-Interscience, New York, 1973, p330.
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17. Strictly speaking, the Δδ method, also known as Imbach's rule, should be applied only to 5’-unsubstituted derivatives, but it is frequently useful for 5’-0-trityl ethers. For the a-isomers in the present study, the actual Δδ values range from 0.11 ppm for 6α to 0.17 ppm for 8α, so the latter is technically a violation, perhaps because of the presence of the trityl group or because of a specific anisotropic effect of the dithiono base. For the (3-isomers, Δδ ranges from 0.21 to 0.24 ppm.
18. H. Ohrui, G. H. Jones, J. G. Moffatt, M. L. Maddox, A. T. Christensen, and S. K. Byram. J. Am. Chem. Soc., 97, 4602 (1975).
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23. In the D-allo- and altroheptonic acid derivatives studied by Ohrui et al. (ref 18), C3’, C4’and C5’ correspond, respectively, to Cl 1, C2’ and C3 fof ribosyl compounds.
24. We are indebted to Drs. J. H. Burchenal and F. A. Schmid of Memorial Sloan-Kettering Cancer Center for providing the in vitro cytotoxicity data.
25. G. D. Kini, E. M. Henry, R. K. Robins, S. B. Larson, J. J. Marr, R. L. Berens, C. J. Bacchi, and J. S. Keithly, J. Med. Chem., 33, 44 (1990).
26. See M. R. Spada, R. S. Klein and B. A. Otter, J. Heterocyclic Chem., 26, 1851 (1989) for some new approaches.
27. The line frequencies of the original spectrum are reproduced satisfactorily when the values given for coupling constants and chemical shifts are used in an nmr simulation program.
28. E. C. Taylor, A. McKillop and R. N. Warrener, Tetrahedron, 23, 891 (1967).
29. The spectrum changes rapidly with time, reflecting the formation of the first intermediate in the conversion of 11.HC1 into 20.