40093-85-4Relevant academic research and scientific papers
Enantioselective synthesis and biological evaluation of 5-o-carboranyl pyrimidine nucleosides
Mourier, Nicolas S.,Eleuteri, Alessandra,Hurwitz, Selwyn J.,Tharnish, Phillip M.,Schinazi, Raymond F.
, p. 2759 - 2766 (1999)
Base-modified carborane-containing nucleosides such as 5-o-carboranyl-2'-deoxyuridine (CDU) when combined with neutrons have potential for the treatment of certain malignancies. Lack of toxicity in various cells, high accumulation in cancer cells and intracellular phosphorylation are desirable characteristics for modified nucleosides used in boron neutron capture therapy (BNCT) for brain tumors and other malignancies. The aim of this work was to synthesize the two β-enantiomers of several 5-o-carboranyl-containing nucleosides. These derivatives may possess favorable properties such as high lipophilicity, high transportability, the ability to be phosphorylated, and resistance to catabolism. β-Isomers of 2',3'-dihydroxynucleosides and analogues containing a heteroatom in the sugar moiety were also synthesized. Carboranyl pyrimidine nucleosides were prepared either from the parent β-D-nucleoside, β-L-nucleoside, or by a coupling reaction. The dioxolane derivative 7Scheme 1Reagents and conditions: (a) 1,1,1,3,3,3-hexamethydisilazane, ammonium sulfate, reflux, 6 h; (b) tin(IV) chloride, CH2Cl2, 0°C, 2h; (c) tetrabutylammonium fluoride, 1 M sol in THF, 0°C, 3h. was prepared by a coupling reaction between protected 5-o-carboranyluracil (8, CU) and the corresponding protected heterocycle. Specific catalysts were used during the N-glycosylation process to favor the formation of the β-isomer. Biological evaluation of these new chiral 5-o-carboranyl pyrimidine derivatives indicated that most of these compounds have low toxicity in a variety of normal and malignant cells and achieved high cellular levels in a lymphoblastoid cell line. Increasing the number of hydroxyl groups on the sugar moiety decreased the cellular accumulation and serum binding to different extents. Five compounds were identified for further biological evaluation as potential agents for BNCT. Copyright (C) 1999 Elsevier Science Ltd.
Synthesis of beta-L-2'-deoxy nucleosides
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Page/Page column 34; 35, (2010/02/11)
An improved process for the preparation of 2′-modified nucleosides and 2′-deoxy-nucleosides, such as, β-L-2′-deoxy-thymidine (LdT), is provided. In particular, the improved process is directed to the synthesis of a 2′-deoxynucleoside that may utilize different starting materials but that proceeds via a chloro-sugar intermediate or via a 2,2′-anhydro-1-furanosyl-nucleobase intermediate. Where an 2,2′-anhydro-1-furanosyl base intermediate is utilized, a reducing agent, such as Red-Al, and a sequestering agent, such as 15-crown-5 ether, that cause an intramolecular displacement reaction and formation of the desired nucleoside product in good yields are employed. An alternative process of the present invention utilizes a 2,2′-anhydro-1-furanosyl base intermediate without a sequestering agent to afford 2′-deoxynucleosides in good yields. The compounds made according to the present invention may be used as intermediates in the preparation of other nucleoside analogues, or may be used directly as antiviral and/or antineoplastic agents.
