Nucleosides transamination

Because aromatic purines and purine nucleosides and free purines such as hypo-xanthine and guanine 242 are readily silylated-aminated [64] (cf Scheme 4.24), it is obvious that 6-membered hydroxy-N-heterocycles are analogously silylated-aminated, with reactivity in the order given in Scheme 4.25 [73] X=OTf is the best leaving group and X=NHSiMe3 (cf the transamination as discussed in Section 4.2.4) is the weakest. 

The sequence of reactions shown in Scheme 15 may be postulated for the biosynthesis of L-garosamine (compare Section 1,3). A nucleotide-bound pentos-4-ulose (probably enzyme-bound) that could arise from the nucleoside diphosphate (NucDP) D-glucuronic acid (compare Scheme 11) is methylated at C-4. Transamination and N-methylation then gives NucDP-L-garosamine. 

A phosphoramidite derivative of A -isobutryT2 -0-methylcytidine has been synthesised in order to decrease the risk of transamination reactions which occur at the C4-position of cytidine when alternatives to ammonia are used for oligonucleotide deprotection. The monomer was prepared from cytidine protected with 1,1,3,3-tetraisopropyldisiloxane. Transient protection of the 2 -hydroxyl as the trimethylsilyl derivative followed by reaction with isobutyryl chloride gave the protected nucleoside which could be reacted with methyl iodide and silver oxide after removal of the transient protection. Suitable protection and derivatisation for synthesis yield the required synthon (131). 

Biosynthesis of the nucleoside skeleton was initially considered to be originated by uridine (or UMP, uridine-5-monophosphate), first oxidized to the 5 -aldehyde, which undergoes aldol condensation with phosphoenolpyruvate to give the octofu-ranuloseuronic acid nucleoside. Subsequent elimination of two carbons (C-7 and C-8 ) followed by transamination would result in the formation of the nucleoside skeleton of the polyoxins. Such a pathway was supported by the isolation of octosyl acid (Figure 4.6) [26, 27]. 

Thus, the first committed step in the nucleoside branch of the blasticidin pathway is formation of 3. The subsequent deoxygenations and transaminations leading to blasti-cidins S and H and to pentopyranine C are summarized in Figure 16. 

The biosynthesis of the nucleoside skeleton of polyoxins has been studied using C- and C-labelled glucose, glycerate, and uridine substrates it was suggested that condensation of uridine as its 5 -aldehyde with phosphoenol pyruvate gives an octofuranuloseuronic acid nucleoside, which loses the two terminal carbon atoms by oxidative elimination followed by transamination to give the required uridyl-5-amino-5-deoxy-D-allofuranosyluronic acid structure. ... 

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