Nucleosides reaction

N -Fmoc serine benzyl ester 2, which could be prepared as shown or purchased commercially, was smoothly converted to the crystalHne O-methylthiomethyl (MTM) ether 3 in high yield via a Pummerer-Hke reaction using benzoyl peroxide and dimethyl sulfide in acetonitrile [39]. This common intermediate was used to synthesize both 5 and 8 [40]. Both Ogilvie [41] and Tsantrizos [42] had reported that I2 was an effective activator with similar MTM ether substrates. The H promoted nucleosidation reaction between O-MTM ether 3 and bis-silylated thymine 4 produced the nucleoamino acid 5 in 60% isolated yield (100% based on recovered 3). Hydrogenolytic deprotection of the benzyl ester with H2, Pd/C in MeOH gave the thymine-containing nucleoamino acid 6 in quantitative yield. 

Quinoxalino[7, 6 2,3]quinoxalin-2-yl Acyclo C-Nucleosides Reaction of l-(A -methyl-A -phenylhydrazono)-D-ara6m )-hexulose (778) with 2,3-diaminophenazine (779) produced 780 (58CB101) (Scheme 204). 

Synthesis of nucleosides. Reaction of shylated heterocycles with a protected 1-0-acyl or 1-0-alkyl sugar in 1,2-dichloroethane with either trimethylsilyl perchlorate or trimethylsilyl trifluoromethanesulfonate, (013)3810802-CF3, as catalyst gives nucleosides in high yield. The reaction is formulated for the reaction of silylated uracil (1) with l-0-acetyl-2,3,5-tri-0-benzoyl- 3-D-ribofuranose (2) either at 22 for a prolonged period or for 4 hr. at reflux temperature. The function of the catalyst is to convert the sugar into the glycosyl... 

The example of a silyl—Hilbert—Johnson nucleosidation reaction in Section 25.3 is presumed to involve an intermediate ribosyl cation that is stabilized by intramolecular interactions involving the C2 benzoyl group. This intermediate blocks attack by the heterocyclic base from the a face of the ribose ring but allows attack on the j8 face, as required for formation of the desired product. Propose a structure for the ribosyl cation intermediate that explains the stereoselective bonding of the base. 

Silylation and Activation of Nucleobases. Base glycosi-dation, using the Vorbriiggen method. and its variations, has been a much exploited synthetic reaction in the formation of many important nucleoside analogs. BSA is used to activate the nucleobases by silylation. The persilylated nucleobases undergo nucleosidations with electrophiles in the presence of Lewis acids, generally tin(IV) chloride or trimethylsilyl trifluoromethane-sulfonate, while phenylselenenyl chloride, N-iodosuccinimide/triflic acid, and iodine have also been used to mediate these reactions. A typical nucleosidation reaction is shown in eq 27. Thymine 1 was treated with BSA in acetonitrile to form the silylated thymine 2 in situ, which is then reacted... 

Numerous applications have been reported. A derivative of the (alkyn-1-yl)nucleosides 295. which have anticancer and antiviral activities, has been synthesized by this reaction. They are also used as chain-terminating nucleosides for DN.A. sequencing[l98,199]. In this reaction, use of DMF as the solvent is most important for successful operation[200]. Only the alkenyl bromide moiety in 2-bromo-3-aceto.xycycloheptene (296) reacts with alkynes without attacking the allylic acetate moiety[201]. 

Regioselective 1,4-azidohydroxylation to give 309 takes place by the reaction of the vinyloxirane 308 with sodium azide[188]. The reaction of the cyclopen-tadiene monoepoxide 310 with sodium azide or purine base offers a good synthetic method for the carbocyclic nucleoside 311(189-191]... 

The protected nucleoside-3-phosphoramidite monomer units such as 671 are used in the solid-phase oligonucleotide synthesis. In the 60mer synthesis, 104 allylic protective groups are removed in almost 100% overall yield by the single Pd-catalyze reaction with formic acid and BuNH2[432], N,(9-protection of uridine derivatives was carried out under pha.se-transfer conditions[433]. 

Treatment of adenosine with nitrous acid gives a nucleoside known as mosine Suggest a reasonable mechanism for this reaction... 

The synthetic scheme typically involves chain-extending addition of protected mononucleotides to a nucleoside bound covalentiy at the 3 -hydroxyl to an inert siUca-based soHd support, such as controlled pore glass (Fig. 11). The initial base-protected 5 -O-dimethoxytrityl (DMT) deoxynucleoside is linked to the soHd support via the reaction of a siUca-bound amino-silane and the -nitrophenylester of the 3 -succinylated nucleoside, yielding a 3 -terminal nucleoside attached to the soHd support (1) (Fig. 11). Chain elongation requites the removal of the 5 -DMT protecting group. 

Uracil reacts with hydrazine to give pyrazol-3(2if)-one (944) and urea N-methyl- and dimethyl-hydrazine behave similarly to give the 2-methyl- and 1,2-dimethyl derivatives. The reactions of hydrazines with uridine and related nucleosides and nucleotides is well studied (67JCS(C)1528). The tautomerism and predominant form of uracil are discussed in Section 2.13.1.8.4. 

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