title: Synthesis and properties of 1-(3'-dihydroxyboryl-2',3'-dideoxyribosyl)pyrimidines.
abstract: Nucleoside analogues having a boronic acid in place of the 3-hydroxyl group of deoxyribose have been synthesized. The synthesis of 3'-dihydroxyboryl-2',3'-dideoxyribose was based on asymmetric homologation of boronic esters with (dihalomethyl)lithium, beginning from a (silyloxymethyl)boronic ester. A change of chiral director is required before introduction of the second stereocenter, and the direct displacement of (S,S)-1,2-dicyclohexyl-1,2-ethanediol by (1S,2S,3R,5S)-pinanediol was used for this purpose. Coupling of the pinanediol ester of the 1-acetoxy-3-dioxyboryl-5-tert-butylsilyloxy deoxyribose analogue with silylated pyrimidine bases was accomplished with trimethylsilyl bromide. The boronic acid nucleoside analogues were not cytotoxic toward Hep G2 (human hepatocarcinoma) cells. Decomposition occurred over a period of several hours at 37 °C, pH 7.4, with liberation of free pyrimidine base.
authors.affiliation: Department of Chemistry, Washington State University, PO Box 644630, Pullman, WA 99164-4630, USA.
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Kim
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Shenglan
authors.initials: S
authors.lastname: Tan
authors.forename: Donald S
authors.initials: DS
authors.lastname: Matteson
authors.forename: William H
authors.initials: WH
authors.lastname: Prusoff
authors.forename: Yung-Chi
authors.initials: YC
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001897:Boronic Acids / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D009705:Nucleosides; D011743:Pyrimidines