Sugar moiety, modifications

The above-described acylation of the sugar moiety of the nucleotide adenosine (3) [2] has been followed by a series of papers reporting on the chemoselec-tive enzymatic modification of natural compounds carrying both hydroxyl and amino groups. In addition to the extensive work on nucleosides developed by Gotor and coworkers [8], the biocatalyzed esterification of the hydroxylated alkaloids castanospermine (4) and 1-deoxynojirimidn (5) should be mentioned. Both compounds were selectively acylated at their C-6 and/or C-2 OH by the protease subtilisin, despite the presence of a potentially more reactive amino functions [9]. 

Except for this particular example, quantitative deprotections were observed for other sugar nitrates without modification of the sugar moiety. Some other Al-deriva-tives such as diphenyl hydrazino substituents introduced by triflate displacement at the C-6 position of galactose residues were photolyzed but in low yields [112]. This group remains of limited interest for any further use in synthesis. 

S. Ogawa and D. Aso, Chemical modification of the sugar moiety of methyl acarviosin synthesis and inhibitory activity of eight analogues containing a 1,6-anhydro bridge,... 

From an additional study, modification or removal of the sugar moiety also has a substantial influence on the cytotoxic potency of eleutherobin and its cross-resistance in Taxol-resistant cells [14]. These structure/activity profiles should be usable for future design of more potent eleutherobin derivatives. 

Since the beginning of the 1990s studies have been concentrated on the synthesis of more functionalized lumazine nucleosides <90Mi 718-06,93MI718-17) with further modifications at the sugar moiety <94MI 718-03). 

While the CHS-CHI-F3H-DFR-AS enzymes form the core flavonoid biosynthetic pathway (Fig. 3.2), every intermediate compound in the pathway can be the subject of complex modifications that include hydroxylations, methylations, esterifications, and decorations with a number of sugar moieties. In addition, many of the core enzymes can utilize various substrates resulting in a pathway that is not linear, but rather a complex grid (Fig. 3.2).2 The diverse forms of flavonoids or anthocyanins that accumulate in any plant under any given condition are the result of a combination of the biosynthetic enzymes being expressed together with their substrate specificity. Over the past few years, the structures of several flavonoid biosynthetic enzymes have been elucidated,1 -20 which opens up unlimited opportunities to understand structure-function relationships and to manipulate the pathway. 

At this pH, the phosphotriesters formed mainly lose alcohol to re-form the phosphodiester, but at higher pH, hydrolysis with chain scission takes place. Alkylation also proceeds at nucleophilic centres on the base and sugar moieties, and the modification likely to cause most damage in vivo has not been defined. Studies involving aflatoxin Bi and benzanthracene derivatives have tended to concentrate on the modification of the bases, to the exclusion of possible effects at the phosphate group, but there is good evidence that the latter should not be ignored. ... 

The syntheses of the 6 -0-(bromopentyl)-substituted allofuranosyl-purine and -pyrimidine phosphoramidite (40a-c) and the 2 -0-[(3-bromopropoxy)methyl] substituted allofuranosyl-purine and -pyrimidine phosphoramidite (41a-c) have been reported. Such modifications of the sugar moiety presented opportunities for the functionalisation of oligonucleotides with a variety of soft nucleophiles while the fully protected sequence was still on the solid support. ... 

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