Dimethoxytrityl protective group

In step 1 of each oligonucleotide-synthesis cycle the 5 -terminal 4,4 -dimethoxytrityl protecting group is removed with trichloroacetic acid, and the support is washed with acetonitrile to prevent dctritylation of the next incoming phosphoramidite. The 4,4 -dimethoxy-... 

J. I. Asakura, M. J. Robins, Y. Asaka, and T. H. Kim, Removal of acetal, silyl, and 4, 4 -dimethoxytrityl protecting groups from hydroxyl functions of carbohydrates and nucleosides with clay in aqueous methanol, J. Org. Chem., 61 (1996) 9026-9027. 

Adinolfi, M, ladonisi. A, Schiattarella, M, An approach to the highly stereocontrolled synthesis of a-glycosides. Compatible use of the very acid labile dimethoxytrityl protecting group with Yb(OTf)3-promoted glycosidation. Tetrahedron Lett., 44, 6479-6482, 2003. 

The 5 -0-dimethoxytrityl protecting group is removed by treatment of the reaction mixture with 3% dichloroacetic acid in dichloromethane. 

Several imidazole functionalised dimethoxytrityl protecting groups have been investigated for their ability to catalyse internucleoside bond formation using phosphate triester chemistry. 

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. 

Step 2 The second step is removal of the DMT protecting group by treatment with dichloroacetic acid in CH2CI . The reaction occurs by an S -l mechanism and proceeds rapidly because of the stability of the tertiary, benzylic dimethoxytrityl cation. 

The dimethoxytrityl ester protecting group is now removed by treatment with mild acid (CCI3CO2H), which is insufficiently reactive to hydrolyse the amide protection of bases, or the cyanoethyl protection of the phosphate. The coupling cycle can now be repeated using a phosphoramidite derivative of the next appropriate nucleoside. The sequences will be continued as necessary until the desired oligonucleotide is obtained. 

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. 

The N-terminal amino group or a Lys residue can easily be used to label the PNA. This can be carried out in solution after purification, or more conveniently, while the PNA is still attached to the resin. Fluorescein and rhodamine are the most common fluorophore labels, while biotin is the most common affinity tag. Fluorescein or rhodamine are usually coupled to the amino group as -OSu esters or isothiocyanates. 4,4 -Dimethoxytrityl-protected biotin and Piv-pro-tected fluorescein have also been coupled to the N-terminus of a PNA as their 1-phenylpyr-azolin-5-one carboxylate esters.147 In 1997 a new fluorescein-conjugated Lys monomer (21, Scheme 12) was described. 48 ... 

B. T. 4,4 -Dimethoxytrityl and 4,4, 4"-tri-methoxytrityl as protecting groups for amino functions selectivity for primary amino groups and application in 15N-labelling. 

---