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

Abstract

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.

Synthesis of Certain 5‐Substituted 2′‐Deoxytubercidin Derivatives

“…Ionic structures can be circumvented if a pyrrolo[2,3-d]pyrimidine is replacing the purine moiety, as in 2'-deoxytubercidin (7a). The latter was obtained from the naturally occurring ribonucleosides by deoxygenation [2] [3], by convergent syntheses [6], and in the form of the 5'-triphosphate by ribonucleotide reductase [4] [5]. It was already incorporated into oligonucleotides [7-lo].…”

7-Deazapurine (Pyrrolo[2,3-d]pyrimidine) 2-Deoxyribonucleosides: Syntheses and Transformations

“…Depending on the structure of the target nucleosides, variations of the Barton-McCombie deoxygenation were used to synthesize 2'-and 3'-deoxyribonucleosides as well as 2'-3'-dideoxyribonucleosides (see also section 4.3) [119][120][121][122][123].…”

Advances in the Synthesis of 7-Deazapurine - Pyrrolo[2,3-d]pyrimidine 2-Deoxyribonucleosides Including D- and L-Enantiomers, Fluoro Derivatives and 2,3-Dideoxyribonucleosides

“…This amino side chain was reacted with an Oacetylprotected succinylfluorescein and deprotected to give 128. In a similar way, 7-deaza-2',3'-dideoxy-7-iodoadenosine (139) was transformed into the corresponding fluorescence-labeled Sanger sequencing reagent 129 (Scheme 46). 7-Deazapurine 2',3'-dideoxyribonucleosides were also used in recently developed DNA sequencing approaches [133], such as MALDI-TOF MS DNA sequencing [134].…”

“…7-Deazapurine 2',3'-dideoxyribonucleosides have been prepared from the corresponding 2'-or 3'-deoxyribonucleosides by the radical-mediated deoxygenation of a 2'- [135][136][137] as well as by elimination of a 3'-mesyloxy group yielding unsaturated nucleosides [79] which were subjected to the catalytic hydrogenation [138][139][140][141]. Also, the deoxygenation of ribonucleosides has been described [138][139][140][141][142] The 7-deazapurine 2',3'-dideoxyribonucleoside 143a was also synthesized by deoxygenation of 3'-deoxyribonucleosides (Scheme 49) [136].…”

“…Also, the deoxygenation of ribonucleosides has been described [138][139][140][141][142] The 7-deazapurine 2',3'-dideoxyribonucleoside 143a was also synthesized by deoxygenation of 3'-deoxyribonucleosides (Scheme 49) [136]. The starting material was 7-deazacordycepin 150 which was prepared as described [138,143].…”