Chlorotrimethylsilane → Adenine

Participants

Reaction Steps

N6 -Benzoyl-9-(2'-fluoro-b-D-ribofuranosyl)adenine was prepared from 9-b-D-arabinofuranosyladenine in a five-step synthesis using a modification of a procedure reported by M. Ikehara at al., Nucleosides and Nucleotides 2:373-385 (1983). Thus, the N6 -benzoyl derivative was obtained in good yield utilizing the method of transient protection with chlorotrimethylsilane. R. A. Jones, J. Am. Chem. Soc. 104:1316 (1982). Selective protection of the 3' and 5'-hydroxyl groups of N6 -Benzoyl-9-β-D-arabinofuranosyladenine with tetrahydro-pyranyl (THP) was accomplished by modification of a literature procedure G. Butke, et al., in Nucleic Acid Chemistry, Part 3:149-152, Townsend, L. B. and Tipson, R. S. eds., (J. Wiley and Sons, New York 1986) to yield N6 -Benzoyl-9-[3', 5'-di-O-tetrahydropyran-2-yl)-β-D-arabino furanosyl] adenine in good yield. Treatment of N6 -Benzoyl-9-[3', 5'-di-O-tetrahydro-pyran-2-yl)-β-D-arabinofuranosyl] adenine with trifluoromethanesulfonic anhydride in dichloromethane gave the 2'-tri-flate derivative N6 -Benzoyl-9-[2'-O-trifluoromethylsulfonyl-3', 5'-di-O-tetrahydropyran-2-yl)-β-D-arabino furanosyl] adenine which was not isolated due to its liability. Displacement of the 2'-triflate group was effected by reaction with tetra-butylammonium fluoride in tetrahydrofuran to obtain a moderate yield of the 2'-fluoro derivative N6 -Benzoyl-9-[2'- fluoro-3', 5'-di-O-tetrahydropyran-2-yl)-β-D-arabino furanosyl]-adenine. Deprotection of the THP groups of N6 -Benzoyl-9-[2'-fluoro-3', 5'-di-O-tetrahydropyran-2-yl)-β-D-arabino-furanosyl] adenine was accomplished by treatment with Dowex-50W in methanol to yield N6 -benzoyl-9-(2'-deoxy-2'-fluoro-β-D-ribofuranosyl)adenine in moderate yield. The 1H-NMR spectrum of 6 was in agreement with the literature values. M. Ikehara and H. Miki, Chem. Pharm. Bull. 26: 2449-2453 (1978). Standard methodologies were employed to obtain the 5'-dimeth-oxytrityl-3'-phosphoramidite intermediates N6 -Benzoyl-9-[2'-fluoro-5'-O-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl] adenine and N6 -Benzoyl-[2'-deoxy-2'-fluoro-5'-O-(4,4'-dimethoxytrityl)] adenosine-3'-O-(N,N-diisopropyl-β-cyanoethylphosphoramidite. K. K. Ogilvie, Can J. Chem. 67:831-839 (1989).

Provenance & Evidence