Nucleic acid related compounds. 24. Transformation of tubercidin 2′,3′-O-orthoacetate into halo, deoxy, epoxide, and unsaturated sugar nucleosides

Treatment of tubercidin (4-amino-7-β-D-ribofuranosylpyrrolo[2,3-d]pyrimidine) (1) with methyl orthoacetate gave the 2′,3′-O-orthoester, 2. Pivalic acid chloride in refluxing pyridine converted 2 into a mixture containing 4-N-pivalamido-7-(3-chloro-3-deoxy-2-O-acetyl-5-O-pivalyl-β-D-xylofuranosyl)pyrrolo[2,3-d)pyrimidine (3a) and the corresponding 2′-O-(4,4-dimethyl-3-pivaloxypent-2-enoyl) (DMPP) compound (3b) via acetoxonium ion intermediates. Treatment of 2 with sodium iodide/pivalyl chloride/pyridine gave the iodo analog (3c) of DMPP derivative 3b plus the 3′,4′-unsaturated nucleoside (5a). Treatment of 3a–c with methanolic sodium methoxide gave the ribo-epoxide 4, which underwent N1 → 3′ intramolecular cyclization readily. Dehalogenation of 3 and deprotection gave 3′-deoxytubercidin (8). Deblocking of 5a gave 5b which was hydrogenated to give 8 plus its 4′-epimer 9. Heating of 3c or 5a produced 4-N-pivalamido-7-(5-pivaloxymethylfuran-2-yl)pyrrolo[2,3-d]pyrimidine (10a). Deblocking of 10a gave 10d which was hydrogenated to give racemic 4-amino-7-(2,3-dideoxy-β-D,L-glycero-pentofuranosyl)pyrrolo[2,3-d]pyrimidine (7,11). The 2′,3′-unsaturated nucleoside (6) was obtained and hydrogenated to produce 2′,3′-dideoxytubercidin (7). Spectroscopic identification of products, epoxide instability, and comparison with other procedures are discussed.