Dimethoxytrityl group

One synthesis cycle is now closed. A new cycle can start with 5 -detritylation (step 1). When the last cycle is closed, the terminal 5-0-(4,4 -dimethoxytrityl) group of the desired oligonucleotide is either removed or left attached before the deprotection, liberation and puriHcation of the product. 

This group, used for 5 -phosphate protection, has hydrophobicity similar to that of the dimethoxytrityl group and thus was expected to assist in reverse-phase HPLC purification of product from failure sequences in oligonucleotide synthesis. The group is cleaved with Bu4N F in DMSO at 70°. ... 

Fig. 19 Basic steps in a cycle of nucleotide addition by the phosphoramidite method in-situ synthesis using ink-jetting. DMTr = dimethoxytrityl group...

It then remains to remove protecting groups and release the product from the support. All of these tasks, except for the removal of the dimethoxytrityl group, are achieved by use of a single deprotection reagent, aqueous base (ammonia). The cyanoethyl groups are lost from the phosphates by base-catalysed elimination, and amide protection of the bases is removed by base-catalysed hydrolysis. The latter process also achieves hydrolysis of the succinate ester link to the support. 

ODMT (ODMTr) is the 4,4 -dimethoxytrityl group, a common -OH protecting group for the carbohydrate moieties in syntheses of polynucleotides. 

O Aqueous dichloroacetic acid is used to remove the dimethoxytrityl group in an SNI reaction. 

A common method for DNA synthesis is the phosphite triester method (Fig. 7-6). A single-stranded oligonucleotide is formed by the sequential creation of diester bonds between the 5 -hydroxyl of one residue and the 3 -phosphate of the next. The 3 -phosphate is activated by substitution by dialkyl phosphoamidite (DPA) and reacts readily with the free 5 -OH of the first nucleotide. To prevent the formation of unwanted linkages the first nucleotide is linked, by the 3 -OH, to a solid support (often silica gel) in a column or funnel the 5 -OH of the second nucleotide is prevented from reacting by a dimethoxytrityl group (DMT). 

We described an unusual oligomer whereby a-amino acids were converted into a-hydroxy acids by oxidative deamination with retention of stereochemistry, followed by reduction to 1,2-diols. The primary alcohol was protected by the dimethoxytrityl group, and the remaining secondary alcohol converted to a phos-phitylating agent. These monomers could then be incorporated into oligomers under the standard conditions of automated DNA synthesis. The resulting molecules retain amino acid side-chains, but have the phosphodiester backbone more familiar to nucleic acids. 

Figure 5-22. Oligodeoxynudeotide synthesis by any unreacted OH groups are blocked in a cap-the phophoramidite method. The free OH group ping step. The protecting dimethoxytrityl group of the previous nucleotide building block reacts is removed in preparation for a new cycle of with the incoming phosphoramidite. After oxida- reaction, tion to the protected phosphotriester,...

This ether is introduced by an acid catalyzed orthoester exchange process with an alcohol. It was developed for protection of the 2-hydroxyl in ribonucleotide synthesis. It is sufficiently stable to dichloroacetic acid, which is used for the cleavage of the dimethoxytrityl group. ... 

The 3,3 -oxybis(dimethoxytrityl) group was developed for protection of ribonucleo-sides, but unexpectedly both the 2, 5 - and 3, 5 -derivatives are formed. The group is introduced using the bis trityl chloride (2,4,6-collidine, AgC104, pyridine, 65°C, 1 h). Acid catalysis is used to remove it. 

Fig. 4.4.8. Separation of protected oligonucleotide on a Partisil PAC column (Cyano-amino-bonded phase) (0.4x25 cm). The mixture chromatographed is the result of the synthesis of a tetramer of cytidine and guanine, protected by, e.g., dimethoxytrityl groups. Eluent Gradient from methanol/dichloromethane (5 95) to (50 50). Reprinted from Ref. 12 with permission.

Figure 3. Protective group strategy in DNA-synthesis by the standard phosphoramidite method on solid support. I Protected 5 -hydroxy group by the DMT (dimethoxytrityl) group, 3 -cyanoethyl-phosphora-midite II, III, IV Protection of nucleobases V Thymine remains unprotected.

Removal of the 5 -0-dimethoxytrityl group from the deoxyribonucleoside attached to the solid support is carried out by treatment of the reaction mixture with 3%dichloroacetic acid in dichloromethane. 

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