Ribonucleotides, protecting groups

Protection of OH groups (2, 271). Preparation of 2 -0-methoxytetrahydro-pyranyl-uridine and -adenosine and of 5 -0-methoxytetrahydropyranyI-thymidine has been described. Yields are 75-85%.2 The protective group has also been used in the preparation of ribonucleotide 2 5 -bisketals. 

After attachment of the building block 97 at the 5 -end, cleavage of the trifluoroacetyl group proceeded by use of aqueous ammonium hydroxide. Such 5 -aminated oligomers have been reacted with various fluorescent dyes [271]. 2 -0-aminoalkylated ribonucleotides allow postsynthetic derivatization after cleavage of the phthalimide protective group 98 [150]. 

Figure 2 Base protecting groups typically used for the synthesis of oligo-ribonucleotides.

Rao MV, Reese CB, Schehlmann V, Yu PS. Use of the l-(2-fluorophenyl)-4-methoxypiperidin-4-yl (Fpmp) protecting group in the solid-phase synthesis of oligo- and poly-ribonucleotides. J Chem Soc Perkin Trans I 43-55, 1993. 

By far the more complicated problem arises in ribonucleotide chemistry. Not only would it be desirable to specifically differentiate the 2 - from the 3 -hydroxyl but any protecting group on the 2 -hydroxyl must be (i) stable enough to remain intact throughout an entire chain synthesis, (ii) innocuous enough not to interfere with subsequent reactions at the 3 -hydroxyl or phosphate functionalities, and... 

The 2 -0-t-butyldimethylsilyl protecting group in ribonucleosides is stable under a variety of conditions used to prepare ribonucleotides, including the chloro-phosphite coupling procedure, which was then used to prepare several 3 -phosphate esters of uridine. 

An 0-protection with B0C2O is performed in the synthesis of 2 -(fert-butyloxy-carbonyl) ribonucleosides. The Boc residue is a particularly suitable protective group for the 2 -OH position in ribonucleotide syntheses, because it offers increased stability towards bases and resistance to 2 3 acyl group transfers [665]. Yields range from 12-48% for 936. 

Protection of Hydroxyl Groups. Photolabile 2 -0-(o-nitrobenzyl) derivatives of various ribonucleotides as well as dinucleotides have been synthesized, and their subsequent photodeprotections, which yield the corresponding alcohols, examined (eq 11). Protection of the anomeric hydroxyl functionality of 2-deoxy-D-ribofuranose has been accomplished using o-NBA (eq 12). This protective group is quite stable to acidic conditions, and has proven invaluable in the synthesis of abasic oligonucleotides. Similar conditions are employed in the synthesis of bis(o-nitrobenzyl) ethers. ... 

Hydroxyl function protecting group (in particular for ribonucleotides). Reagent for oxid. decyanations. Silylation reagent for use in chromatog. Mp 91.5°. BP733 125°. 

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