7‐Desaza‐Isostere von 2′‐Desoxyxanthosin und 2′‐Desoxyspongosin — Synthese via Glycosylierung von 2,4‐Dichlor‐7H‐pyrrolo[2,3‐d]pyrimidin

Abstract

Due to the reactivity of the chromophore halogens removal of the toluoyl residues by sodium methoxide resulted in rapid displacement of the chloro substituents which prevented the isolation of the free deoxyriboside of 3b and led to the 2,4-dimethoxynucleoside 7. As shown by the conversion of 5a into 2, regioselective displacement of the halogen in position 4 can be accomplished under conditions which maintain the protecting groups of the sugar moiety.In einer von uns unlangst durchgefuhrten Untersuchung konnten wir zeigen, daB 2,CDichlor-7H-pyrrolo[2,3-d]pyrimidin (3 b) in guter Ausbeute regioselektiv an N-7 mit l-Brom-2,3,5-tri-Obenzylarabinofuranose glycosyliert werden kann. Das dabei entstehende Arabinonucleosid besitzt ein hohes Potential fur die Synthese von Nucleosiden'). Im folgenden versuchen wir den Chromophor 3b auch fur die Darstellung von P-~-2'-Desoxynucleosiden, hier speziell fur die Synthese von 7-Desaza-2'-desoxyxanthosin (1 a) und 7-Desaza-2'-desoxyspongosin (2) einzusetzen.Die Purin-Stammnucleoside von 1 a und 2 sind seit langerem bekannt. 2'-Desoxy-2-methoxyadenosin2) wurde von Broom et. al. 3, aus einem 2,4-Dichlorpurin-P-~-2'-desoxyribosid durch selektiven Halogenaustausch erhalten, wahrend 2'-Desoxyxanthosin enzymatisch mittels Purinnucleosid-Phophorylase aus Xanthin und Desoxyrib~se-l-phosphat~~~) hergestellt wurde.

5-Aza-7-deaza-2′-deoxyguanosine: Oligonucleotide Duplexes with Novel Base Pairs, Parallel Chain Orientation and Protonation Sites in the Core of a Double Helix

“…to guanine) in the protonated form. [29,30] Appropriate base an oligonucleotide single strand prior to binding to its pairing is possible with other bases providing a proton to complement so that it more resembles the bound confor-N-1 of the 5-aza-7-deazaguanine moiety. Stable, tridentate mation.…”

Oligonucleotides Containing 7-Deaza-2′-deoxyxanthosine: Synthesis, Base Protection, and Base-Pair Stability

“…Part). The 13 C-NMR chemical-shift assignment was made by means of gated-decoupled 13 C-NMR spectra as well as by comparison with the other related 7-deazapurine nucleosides [8] [23]. The assignments for C(2) and C(6) are tentative.…”

“…An enzymatic synthesis of 1 from 2'-deoxyisoinosine has been reported by our laboratory [7]. Contrary to the labile xanthine nucleoside 1, the glycosylic bond of 7-deaza-2'-deoxyxanthosine (3), which was first synthesized in our laboratory, is resistant to depurination even under strong acidic conditions [8]. Both, 2'-deoxyxanthosine (1) and 7-deaza-2'-deoxyxanthosine (3), form oligonucleotide duplexes and triplexes [9 -12].…”

“…[8] (3; 200 mg, 0.75 mmol) in anh. pyridine (5 ml) was (i-Pr) 2 A C H T U N G T R E N N U N G EtN (400 ml, 2.33 mmol) and diphenylcarbamic chloride (490 mg, 2.11 mmol) while stirring.…”

Synthesis of 2′‐Deoxyisoinosine and Related 2′‐Deoxyribonucleosides

“…As starting material, 4-chloro-2-methoxypyrrolo[2,3-d]pyrimidine (5) [8] was used. It was already glycosylated under liquid-liquid phase-transfer conditions [9] but was now reacted with halogenose 6 in MeCN in the presence of tris[2-(2-methoxyethoxy)ethyI]amine (TDA-1) and powdered KOH [ 101 (Scheme I ) . Under these conditions, the reaction was stereoselective (+ 7), and the glycosylation yield was increased from 67 [9] to 86%.…”