Nucleic acid related compounds. 25. Syntheses of arabino, xylo, and lyxo-anhydro sugar nucleosides from tubercidin ribo-epoxide

Abstract

Treatment of the trans iodohydrin acetate, 4-amino-7-(3-iodo-3-deoxy-2-O-acetyl-5-O-[2,5,5-trimethyl-1,3-dioxolan-4-on-2-yl]-β-D-xylofuranosyl)pyrrolo[2,3-d]pyrimidine (2) with metha-nolic ammonia gave 2′,3′-anhydrotubercidin (3) in 96% yield. N4,N4,O5′-Tribenzoylation of 3 gave 4, which is stabilized against intramolecular cyclization. Treatment of 4 with boron tri-fluoride etherate (3′,5′-benzoxonium ion formation) followed by deblocking gave 4-amino-7-β-D-xylofuranosylpyrrolo[2,3-d]pyrimidine (5) in 91% overall yield from tubercidin (1). The 3′,5′-O-isopropylidene derivative (6a) of 5 was mesylated to give 6b which was deprotected in acid and the resulting trans hydroxy mesylate was treated with base to give 4-amino-7-(2,3-anhydro-β-D-lyxofuranosyl)pyrrolo[2,3-d]pyrimidine (7). This lyxo epoxide was treated with sodium benzoate in DMF to give 4-amino-7-β-D-arabinofuranosylpyrrolo[2,3-d]pyrimidine (8). Biochemical, spectroscopic, and chemical properties of these semisynthetic antibiotic analogues of biologically active adenine nucleosides are discussed.