Nucleosides selective oxidation

Nucleoside N -oxides have proved useful in preventing intramolecular cyclizations during manipulation of the sugar moiety. A key step is the reductive removal of the oxide when needed. In the presence of Raney nickel, the oxide can be reduced selectively even when such easily reduced substituents as iodo are present. Azides, however, are reduced concomitantly with the oxide 105). 

An extension of this methodology was used In another approach (16) to the octosyl acids and ezomyclns (Figure 10). In this sequence, D-galactose was transformed Into the 2-0-acetyl derivative 57. Transformation to the acyclic nucleoside derivative and selective oxidation then gave sulfoxide 58. Elimination afforded the trans olefin 59 whereupon solvolysis followed by epoxldatlon and acid-catalyzed cycllzatlon produced and In a 1 2 ratio respectively. The H-NMR spectra showed each to contain a l, 2 -trans configuration, and that the minor Isomer was the required 6-D-nucleoslde, while the major product was the a-D-nucleoslde. 

The trivalent phosphorus atom in triphenylphosphine is quantitatively oxidized by in-situ-generated or isolated DMD, to afford triphenylphosphine oxide under a variety of conditions Recently, the selective oxidation of the phosphite functionality in nucleosides was reported to produce the corresponding nucleotides in nearly quantitative yields". One example of such an oxidation is shown in equation 16, to illustrate that this phosphorus oxidation may offer an expedient way of preparing unusual nucleotides. 

Beginning with the enantiomer of 27, the reaction sequence outlined in Fig. 4 was repeated, leading to compound 14 (63). Selective oxidation of 14 afforded the carboxylic acid 23(63). The arsenic-containing nucleoside 25 was obtained by treating 5 -chloro-5 -deoxyadenosine with excess dimethylarsinosodium and oxidation of the resultant arsine (63). 

Selective oxidation of nucleosides by photolysis of pyruvic esters has also been reported.43,44 This photochemical procedure45,46 is particularly useful for the oxidation of fragile molecules, and has been used to prepare protected 3 -ketothymidines. ... 

In numerous synthetic studies it has been demonstrated that DMP can be used for a selective oxidation of alcohols containing sensitive functional groups, such as unsaturated alcohols [297,1215-1218], carbohydrates and polyhydroxy derivatives [1216, 1219-1221], silyl ethers [1222,1223], amines and amides [1224-1227], various nucleoside derivatives [1228-1231], selenides [1232], tellurides [1233], phosphine oxides [1234], homoallylic and homopropargylic alcohols [1235], fluoroalcohols [1236-1239] and boronate esters [1240]. Several representative examples of these oxidations are shown below in Schemes 3.349-3.354. Specifically, the functionalized allylic alcohols 870, the Baylis-Hillman adducts of aryl aldehydes and alkyl acrylates, are efficiently oxidized with DMP to the corresponding a-methylene-p-keto esters 871 (Scheme 3.349) [1217]. The attempted Swern oxidation of the same adducts 870 resulted in substitution of the allylic hydroxyl group by chloride. 

Some strongly basic anion exchange resins in the periodate form have been used to selectively oxidize ribofuranosyl nucleosides, in the presence of glucopyr-anosides and galactopyranosides, to the corresponding ring-opened 2 3 -dialde-hydes. ... 

Various nucleoside dialdehydes, obtained by periodate cleavage, have been tested for antitumour activity. The periodate forms of strongly basic anion exchangers have been used for the selective oxidation of ribofuranosyl nucleosides in the presence of galacto- and gluco-pyranosides. Routes have been developed for the regioselective synthesis of both adenosine monoaldehydes the previously-unknown 3 -monoaldehyde 266 was made from the dialdehyde by selective protection of the 3 -aldehyde as the JV,A -diphenylimidazolidine derivative, followed by borohydride reduction. ... 

Photolysis of pyruvic esters (see p. 129) has been used for the selective oxidation ol nucleosides. For example, this photochemical process was used to prepare 5 -0-trityl(or benzoyI)-3 -ketothymidine (610) from either 5 -0-trityl(or benzoyl)-thymidine (Scheme 93) or their 3 -epimers. The 5 -0-trityl-3 -kctonucleoside (610 ... 

Joffe A, Geacintov NE, Shafirovich V (2003) DNA lesions derived from the site selective oxidation of guanine by carbonate radical anions. Chem Res Toxicol 16 1528 1538 Masuda M, Suzuki T, Friensen MD, Ravanat JL, Cadet J, Pignattelli B, Nishino H, Ohshi-ma H (2001) Chlorination of guanosine and other nucleosides by hypochlorous acid and myeloperoxidase of activated human neutrophils catalysis by nicotine and trimethylamine. J Biol Chem 276 40486 10496... 

Phenylglyoxal and alkoxyphenylglyoxals react selectively with the guanine moiety of nucleosides and nucleotides in phosphate buffer (pH 7.0) at 37°C for 5-7 min to give the corresponding fluorescent derivatives [12-15], as shown in Figure 6. Other nucleic acid bases and nucleotides (e.g., adenine, cytosine, uracil, thymine, AMP, CMP) do not produce derivatives under such mild reaction conditions. The fluorescent derivative emits chemiluminescence on oxidation with di-methylformamide (DMF) and H202 at pH 8.0-12 [14, 15],... 

The aldehyde 38 was obtained from 35, by way of 36 and 37, by the carbodiimide—dimethyl sulfoxide oxidation procedure52 in the presence of 3-(3-dimethylaminopropyl)-l-ethylcarbodiimide hydrochloride (EDAC)53 and dichloroacetic acid. It was isolated in the form of its crystalline 1,3-diphenylimidazolidine derivative (39) by trapping the freshly prepared aldehyde 38 with N,N -diphen-ylethylenediamine. (This reagent was developed by Wanzlick and Lochel54 for the selective derivatization of aldehydes, and has been exploited for the isolation of nucleoside 5 -aldehydes55 and other aldehydo derivatives of carbohydrates by Moffatt and coworkers.52(b))... 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

Dichlorobenzimidazole nucleosides of type 1.2 were prepared (94MI4). The thymine analog, upon selective protection, oxidation, and... 

The synthetic procedure currently used consists in the direct oxidation of an isolated hydroxyl group in the sugar moiety of suitably protected nucleosides. In the meantime, the synthesis of some keto derivatives of aldopentose nucleosides by selective-elimination processes has been reported.4 8... 

Nitrobenzotriazole possessing an excellent herbicidal activity [628] has been prepared on oxidizing 2-acetylamino-6-nitrophenylhydrazine with chlorine [522], A-Chloro derivative of 4-nitrobenzotriazole is used as an oxidizer of alkylamines [629], l-Acetyl-4-nitrobenzotriazole is the excellent selective A-acetylation agent for nucleosides [630],... 

---