Ribonucleosides acetals

The CPTr group was developed for the protection of the 5 -OH of ribonucleosides. It is introduced with CPTrBr/AgN03/DMF (15 min) in 80-96% yield and can be removed by ammonia followed by 0.01 M HCl or 80% AcOH. It can also be removed with hydrazine and acetic acid. ... 

The adamantoate ester is formed selectively from a primary hydroxyl group (e.g., from the 5 -OH in a ribonucleoside) by reaction with adamantoyl chloride, Pyr (20°, 16 h). It is cleaved by alkaline hydrolysis (0.25 N NaOH, 20 min), but is stable to milder alkaline hydrolysis (e.g., NH3, MeOH), conditions that cleave an acetate ester. ... 

The greater hydrolytic lability of O-formyl than of O-benzoyl groups has been used in the preparation of ribonucleoside 2 -acetal 5 -esters.153 Acid-catalyzed reaction between 5,6-dihydro-4-methoxy-2//-pyran and N2-benzoyl-5 -0-benzoyl-3 -0-formylguanosine, followed by selective deformylation of the product with dilute methano-lic ammonia, gave N2-benzoyl-5 -0-benzoyl-2 -0-(4-methoxytetrahy-dropyran-4-yl)guanosine. 

Heating the imidazole ribonucleoside (656) with acetic anhydride and pyridine produced (657). Propionic anhydride reacted comparably (75JOC2920). The same ring system can be prepared by treating uric acid (658) with isobutyric anhydride. Cleavage and rearrangement... 

Similarly to other purine ribonucleosides, isoguanosine can be brominated with bromine in acetic acid to give 8-bromoisoguanosine (10) bromination in buffered aqueous medium, which has been used in the case of adenosine or guanosine, is not successful due to oxidation. ... 

Some ribonucleoside and nucleotide separations on 1.5x34 cm columns of DEAE-cellulose eluted with 0.09 M sodium acetate, 0.2 M acetic acid pH 4.4 have been described (Whatman Data Sheet DS/13). 

T-O-Deacylation of ribonucleosides.1 This salt (1) is useful for regioselective 2 -O-deacylation of 2, 3, 5 -triacyl derivatives of ribonucleosides. Hydrazinium acetate is somewhat less effective. 

Protective group. In the presence of an acid the reagent reacts with the 2 -hydroxyl group of a ribonucleoside 3 -phosphate-5 -acetate to give the a-ethoxy-ethyl derivative. The a-ethoxyethyl group is preferred to the tetrahydropyranyl... 

You may be surprised by the stereoselectivity of this coupling. The benzoate on the 2 position actually participates 157 after the acetate is lost 156 so that the silylated pyrimidine has to attack from the top face 159. Silylated cytosine reacts rather like a silyl enol ether. This type of stereochemical control applies only to ribonucleosides and is more difficult to achieve without the 2 OH group. 

In most of the syntheses of ribonucleoside 5 -phosphates that we have described thus far, 2, 3 -0-isopropylidene or 2, 3 -0-benzylidene acetals of nucleosides have been employed as starting materials, to permit selective phosphorylation on 0-5. Such protecting groups, in common with acetals generally, are removable with dilute, aqueous, mineral acid. In some cases, however, the marked instability of the nucleotide derivative to acid precludes the use of these acetals, as the conditions required for removal of the acetal group are too strong. p-Substituted benzylidene derivatives (97) or (98)122.146,146 have shown utility, as deacetalation of these derivatives is readily accomplished under milder acidic conditions. A series of... 

The reaction of ribonucleosides with ethyl orthoformate or methyl orthoacetate under acid-catalyzed conditions affords the 2, 3 -0-(ethoxy-methylidene) (99, R = H, R = CsHs) and the 2, 3 -0-(methoxy-ethylidene) (R = CHs, R = CHs) acetals, respectively. These acetals... 

An interesting acid-labile linker has been designed for a non-standard RNA synthesis with 5 -Fmoc protection [303] and methyl phosphoramidite chemistry by Palom et al. [304], The authors prepared an acetal anchor for the ribonucleoside 2, 3 -diol group (Figure 19.15) by the reaction of 5 -Fmoc-uridine with 4-formyl-phenoxyacetic acid, and attached it to LCAA-CPG (30-40 gmolg"1). The nucleoside can be detached from this support in ca. 70% yield by overnight treatment with dilute aqueous HC1, pH 2, conditions now believed to be too drastic for RNA. 

An especially mild method, suited to the acetonation of ribonucleosides, using 1-ethoxy-l-methylethylene in A,A-dimethylformamide has been described by Chlddek and Smrt. A more convenient method adopted by these authors was to add ethyl orthoformate and an acid catalyst to the acetone, thus forming the diethyl acetal of acetone, which then reacts rapidly with the glycol group in the ribonucleoside. By an identical prq-... 

Interaction of a ribonucleoside with dibromomethane under phase-transfer conditions gave 23 - -methylene acetals. In the case of the uridine derivative, glycosyl cleavage occurred in acid before complete deprotection, and, since purine nucleosides are more labile, methylene acetals are unlikely to be of any practical... 

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