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Synthesis of 1‐[(3‐Halo‐1‐Hydroxy‐2‐Propoxy)methyl]uracil and Thymine as Potential Antiviral Agents
Author(s) -
Wang EngChi,
Chen HourYoung,
Tzeng CherngChyi
Publication year - 1993
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.199300012
Subject(s) - chemistry , halogen , methyl iodide , acetic acid , medicinal chemistry , anhydrous , iodide , nuclear chemistry , acetone , thymine , organic chemistry , alkyl , dna , biochemistry
3′‐Halogen acyclonucleoside analogs have been prepared. The starting material, benzyl glycidyl ether (5) , prepared from eplchlorohydrin and sodium benzyloxidc, underwent ring opening by soft halogen ions to give l‐benzyloxy‐3‐fluoro‐2‐propanol (6) , l‐bcnzyloxy‐3‐chloro‐2‐propanol (7) , and l‐benzyloxy‐3‐ bromo‐2‐propanol (8) respectively. The treatment of 5 with lithium iodide in the presence of acetic acid provided 1‐benzyloxy‐3‐iodo‐2‐propanol (9) . The treatment of 8 with sodium iodide in anhydrous acetone also produced l‐benzyloxy‐3‐iodo‐2‐propanol (9) . Chloromethylation of these halohydrins 6‐9 using paraformaldehyde and hydrogen chloride gas produced the chloromcthyl ethers 10‐13 . These chloromethyl ethers without further purification were allowed to react with the silylated bases 16‐17 , previously prepared by silylating the bases 14‐15 with HMDS in the presence of ammonium sulfate to give 1‐ [(l‐benzyloxy‐3‐halogen‐2‐propoxy)methyl]uracils and thymines 19‐25 . The target compounds 26‐33 were obtained respectively after the debcnzylation of 18‐25 . Compounds 26, 27, 30 and 31 had no significant cell toxicity in the range of concentrations 0.001‐20 mM. Compounds 26, 27, 28 and 29 have no significant activity against HSV II (for less than 2 mM there is a cytopathic effect). Compounds 30, 31, 32 and 33 show no activity against HSV II virus even at the level 20 mM.