Abstract
Novel fluoro-substituted apio dideoxynucleosides ((±)-3a and (±)-3b) were efficiently synthesized starting from 1,3-dihydroxyacetone via Horner-Emmons olefination as a key step. Cyclization of fluoro ester (±)-6 under acidic conditions to the fluorolactone was smoothly proceeded in favor oftrans-fluorolactone due to the favorable transition state with equatorial hydroxymethyl substituent. Unfortunately, the final nucleosides (±)-3a and (±)-3b were found to be inactive against several viruses such as HIV-1, HSV-1, HSV-2 and HCMV.
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Bamford, M. J., Humber, D. C., and Storer, R. Synthesis of (±)-2-oxa-carbocyclic-2,3-dideoxynucleosides as potential anti-HIV agents.Tetrahedron Lett., 32, 271–274 (1991).
Beach, J. W., Jeong, L. S., Alves, A. J., Pohl, D., Kim, H. O., Chang, C. N., Doong, S. L., Schinazi, R. F., Cheng, Y.-C., and Chu, C. K. Synthesis of Enantiomerically Pure (2R,5S)-(−)-1-(2-hydroxymethyl-L-oxathiolan-5-yl) cytosine as a Potent Antiviral Agent against Hepatitis B Virus (HBV) and Human Immunodeficiency Virus (HIV).J. Org. Chem., 57, 2217–2219 (1992).
Jeong, L. S., Schinazi, Beach, R. F., Kim, H. O., Nampalli, S., Shanmuganathan, K., Alves, A. J., McMillan, A., and Chu, C. K. Asymmetric Synthesis and Biological Evaluation of β-L-(2R,5S)-and α-L-(2R, 5R)-1,3-Oxathiolanyl Pyrimidine and Purine Nucleosides as Potential Anti-HIV Agents.J. Med. Chem., 36, 181–195 (1993).
Jeong, L.S., Lee, Y. A., Moon, H. R., and Chun, M. W., Synthesis and antiviral activity of apio dideoxynucleosides with azido or amino substituent.Nucleosides & Nucleotides, 17, 1473–1478 (1998).
Jeong, L. S., Kim, H. O., Moon, H. R., Hong, J. H., Yoo, S. J., Choi, W. J., Chun, M. W., and Lee, C.-K. Syntheses and Structure-Activity Relationships of Novel Apio and Thioapio Dideoxydidehydro Nucleosides as Anti-HCMV Agents.J. Med. Chem., 44, 806–813 (2001).
Schinazi, R. F., Chu, C. K., Peck, A., McMillan, A., Mathis, R., Cannon, D., Jeong, L. S., Beach, J. W., Choi, W.-B., Yeola, S., Liotta, D. C. Activities of the Four Optical Isomers of 2,3-Dideoxy-3-thiacytidine (BCH-189) against Human Immunodeficiency Virus Type 1 in Human Lymphocytes.Antimicrob. Agents Chemother., 36, 672–676 (1992).
Terao, Y., Akamatsu, M., Achiwa, K., Synthesis of chiral 3-substituted γ-lactones and 9-furanosyl-adenine from (R)-2-(2,2-diethoxyethyl)-1,3-propanediol monoacetate prepared by lipase-catalyzed reaction.Chem. Pharm. Bull., 39, 823–825 (1991).
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Hong, J.H., Kim, H.O., Moon, H.R. et al. Synthesis and antiviral activity of fluoro-substituted apio dideoxynucleosides. Arch. Pharm. Res. 24, 95–99 (2001). https://doi.org/10.1007/BF02976474
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DOI: https://doi.org/10.1007/BF02976474