A general synthetic method of 5-carboranyluracil nucleosides with potential antiviral activity and use in neutron capture therapy

Article abstract of DOI:10.1080/07328319708002564

Previous biochemical and pharmacological studies indicated that 5-o- carboranyl-2'-deoxyuridine is a lead candidate for boron neutron capture therapy. This prompted the development of a rapid and stereoselective N¹- glycosylation reaction of silylated 5-o-carboranyluracil with a variety of protected sugars. The key intermediate, 5-o-carboranyluracil (6), was prepared from 5-iodouracil in six steps. A novel coupling procedure of the 2,4-dimethoxy-5-ethynylpyrimidine (4) with decaborane without activator was used. Silylated 6 was coupled with a variety of carbohydrates under mild conditions to produce several carborane containing nucleosides. In each case, the stereochemistry and stereoselectivity of the glycosylation reaction was not affected by the presence of the carborane at the 5-position of the uracil and produced exclusively closo [closo-1,2-C₂B₁₀H₁₂ cage] nucleosides. This was confirmed by X-ray structure determination of racemic 5-carboranyl- 2',3'-dideoxy-3'-thiauridine. This compound demonstrated an anti-conformation with the oxathiolane ring in a pseudo C-2'-endo conformation. The toxicity profile of the new compounds and their precursors was determined in three cell culture systems, two of human origin (PBM and CEM cells) and one of monkey origin (Vero cells). The compounds were also evaluated for their potential antiviral activity against human immunodeficiency virus and herpes simplex virus in vitro. 5-o-Carboranyl-xylofuranosyluracil (12) demonstrated low toxicity in culture and in mice.

Full text of DOI:10.1080/07328319708002564

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Nucleosides and Nucleotides
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A General Synthetic Method of 5-
Carboranyluracil Nucleosides with
Potential Antiviral Activity and use in
Neutron Capture Therapy
Naganna M. Goudgaon a c , Yahya A. El-Kattan a b c , Xiaoyang Xia b ,
Jeff McAtee b , José Soria b , Shiow-Jyi Wey b , Dennis C. Liotta b &
Raymond F. Schinazi a c
a Departments of Pediatrics , Emory University , Atlanta, Georgia,
30322
b Department of Chemistry , Emory University , Atlanta, Georgia,
30322
c Veterans Affairs Medical Center , Decatur, Georgia, 30033, USA
Published online: 23 Aug 2006.
To cite this article: Naganna M. Goudgaon , Yahya A. El-Kattan , Xiaoyang Xia , Jeff McAtee , José
Soria , Shiow-Jyi Wey , Dennis C. Liotta & Raymond F. Schinazi (1997) A General Synthetic Method of
5-Carboranyluracil Nucleosides with Potential Antiviral Activity and use in Neutron Capture Therapy,
Nucleosides and Nucleotides, 16:12, 2133-2150, DOI: 10.1080/07328319708002564
To link to this article: http://dx.doi.org/10.1080/07328319708002564
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