O⁶-(Benzotriazol-1-yl)inosine Derivatives:  Easily Synthesized, Reactive Nucleosides

Abstract

Synthetic procedures and characterization data for compounds not described in the manuscript. 3',5'-Di-O-(tert-butyldimethylsilyl)-O 6 -methyl-2'-deoxyinosine (7a).In a clean, dry reaction vial equipped with a stirring bar were2'-deoxyinosine (5a) (59.8 mg, 0.100 mmol), Cs 2 CO 3 (65.2 mg, 0.200 mmol) and methanol (1.0 mL). The reaction mixture was flushed with N 2 and stirred at room temperature for 1 h after which the mixture was evaporated to dryness. Chromatographic purification (SiO 2 , elution with 20% EtOAc in hexanes) afforded 38.0 mg (77% yield) of the title compound as a clear gum. R f (20%

Synthesis and Utility of 2‐Halo‐O6‐(benzotriazol‐1‐yl)‐Functionalized Purine Nucleosides

“…Although the O 6 -(benzotriazol-1-yl)-substituted guanosine (2a) was difficult to extract from NMP due to the water solubility of both species, this problem was largely overcome by submitting the crude reaction mixture directly to a silica column and eluting with a CH 2 Cl 2 /MeOH gradient (1:0 Ǟ 9:1). This observation of aqueous uptake and poor solubility of inosine was also noted by Bae et al [8] This outcome is comparable to the previously reported reaction between TBS-protected guanosine and BOP in the presence of DBU (59 % vs. 65 % yield). [11] [3] [a] Isolated yield after chromatography.…”

“…However, this has not been achieved for unprotected guanosine until now. In a related study, Bae et al [8] also showed that it was possible to generate O 6 -(benzotriazol-1-yl)inosine without protection of the 2Ј-, 3Ј-and 5Ј-hydroxy groups in a yield of 53 %. In all cases, these O 6 -(benzotriazol-1-yl)purine nucleosides were demonstrated to be highly versatile synthetic intermediates that readily underwent substitution in the 6-position with a range of nucleophiles and could also be elaborated further in the 2-position.…”

“…For a number of years, the versatility and efficiency of phosphonium-mediated coupling of tautomerizable heterocycles, [6] in particular nucleosides, has generated widespread attention. [7][8][9][10][11][12] Previous work by Lakshman et al [11] as well as our group [3] has shown that it is possible to convert certain protected guanosine derivatives to the corresponding O 6 -(benzotriazol-1-yl)guanosines using BOP and DBU. More specifically, TBS-protected guanosine was found to undergo this conversion in 65 % yield, while 2Ј,3Ј-isopropylidene-protected guanosine-5Ј-N-ethylcarboxamide gave a 95 % yield of the corresponding O 6 -(benzotriazol-1-yl) derivative.…”

Pyrenylmethyldeoxyadenosine: A 3′‐Cap for Universal DNA Hybridization Probes

“…To facilitate combinatorial work, a solid-support bound version of the literature-known inosine building block 26 [33] (Scheme 6) was developed. First, the methodology was tested on 27 in solution (Scheme 5 and Scheme S1, Supporting Information).…”

“…First, the methodology was tested on 27 in solution (Scheme 5 and Scheme S1, Supporting Information). [33] Oxybenzotriazolide 27 was treated with 4-hydroxystilbene, yielding the expected 6-(aryloxy)purine (28) in 99 % yield. This encouraged us to succinylate 26 (Scheme 6) to 29, and to couple it to sarcosine-bearing controlled pore glass 30, [34] to obtain support 31.…”