Chlorotrimethylsilane → Adenine

Participants

Reaction Steps

N6-Benzoyl-9-(2′-fluoro-b-D-ribofuranosyl) adenine was prepared from 9-β-D-arabinofuranosyladenine in a five-step synthesis using a modification of a procedure reported by Ikehara at al. [Nucleosides and Nucleotides, 2, 373-385 (1983)]. The N6-benzoyl derivative was obtained in good yield utilizing the method of transient protection with chlorotrimethylsilane. 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 tetrahydropyranyl (THP) was accomplished by modification of the literature procedure according to Butke et al. [Nucleic Acid Chemistry, Part 3, p.149, L. B. Townsend and R. S. Tipson, 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-tetrahydropyran-2-yl) -β-D-arabino-furanosyl]adenine with trifluoromethanesulfonic anhydride in dichloromethane gave the 2′-triflate derivative N6-Benzoyl-9-[2′-O-trifluoromethylsulfonyl-3′,5′-di-O-tetrahydropyran-2-yl) -β-D-arabinofuranosyl]adenine which was not isolated due to its lability. Displacement of the 2′-triflate group was effected by reaction with tetrabutylammonium 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-arabinofuranosyl]adenine. Deprotection of the THP groups of N6-Benzoyl-9-[2′-fluoro-3′,5′-di-O-tetrahydro-pyran-2-yl) -β-D-arabinofuranosyl]adenine was accomplished by treatment with Dowex-50W in methanol to yield N6-benzoyl-9-(2′-deoxy-2′-fluoro-β-D-ribofuranosyl) adeninein moderate yield. The 1H-NMR spectrum was in agreement with the literature values. [Ikehara and Miki, Chem. Pharm. Bull., 26, 2449 (1978)]. Standard methodologies were employed to obtain the 5′-dimethoxytrityl-3′-phosphoramidite intermediates N6-Benzoyl-9-[2′-fluoro-5′-O-(4,4′-dimethoxytrityl) -β-D-ribo-furanosyl]adenine and N6-Benzoyl-[2′-deoxy-2′-fluoro -5′-O-(4,4′-dimethoxytrityl)]adenosine-3′-O-(N,N-diisopropyl-β-cyanoethylphosphoramidite. [Ogilvie, Can J. Chem., 67, 831-839 (1989)].

Provenance & Evidence