Improved synthesis of oligodeoxyribonucleotide using 3-methoxy-4-phenoxybenzoyl group for amino protection

Abstract

3-Methoxy-4-phenoxybenzoyl group has been used for the protection of exocyclic amino group of nucleosides. In case of 2'-deoxycytidine it has been found to be highly selective under controlled conditions. The N-protected derivatives of 2'-deoxyadenosine and 2 '-deoxyguanosine have been found to be suf ficiently stable towards acids minimising depurination under conditions of synthesis of oligodeoxyribonucleotide on solid support via phosphotriester approach. The high lipophilicity of the group and milder deprotection conditions are additional advantages.

The final deprotection step in oligonucleotide synthesis is reduced to a mild and rapid ammonia treatment by using labile base-protecting groups

“…Besides, we can also mention among other compounds : the 2-nitrophenylsulfenyl (NPS) (10), isovaleryl, pivaloyl, propionyl (5,11), 2-methylpropanoyl (12), nitrophenylethoxycarbonyl (13), dialkylformamidines (14), succinyl, phthaloyl and substitued (15), and more recently (3methoxy 4-phenoxy)benzoyl (16).…”

Nucleobase Protection of Deoxyribo‐ and Ribonucleosides

“…(4) The exocyclic amino group of cytidine and deoxycytidine can be directly acylated using activated esters (Igolen and Morin, 1980), acid chlorides (Mishra and Misra, 1986, and references therein), or alkyloxycarbonylbenzotriazoles (Himmelsbach et al, 1984). (5) Himmelsbach et al, 1984Pfleiderer et al, 1985Pfister and Pfleiderer, 1989 -Happ et al, 1987Hagen and Chládek, 1989Heikkilä and Chattopadhyaya, 1983Marugg et al, 1984Nagaich and Misra, 1989 4-nitrophenylethyloxycarbonyl Nyilas et al, 1988 G (N2); A (N6); C (N4) Brown et al, 1989Rao et al, 1987Tanimura et al, 1988Schaller et al, 1963Balgobin et al, 1981 Köster et al, 1981Sinha et al, 1993Boal et al, 1996 4-(tert-butyl)phenoxyacetyl diphenylacetyl 3,4-dichlorobenzoyl 3-methoxy-4-phenoxybenzoyl and removal of N-acyl protecting groups can also be achieved by enzymatic methods (Prasad and Wengel, 1996).…”

“…The original method by Ti et al () for installation of protecting groups has also been further simplified by eliminating the use of ammonium hydroxide during work‐up. Several approaches have been reported: (1) The exocyclic amino groups of cytidine and deoxycytidine were directly acylated using activated esters (Igolen & Morin, ), acid chlorides (Mishra & Misra, , and references therein), or alkyl oxycarbonyl benzotriazoles (Himmelsbach, Schulz, Trichtinger, Charubala, & Pfleiderer, ). (2) Site‐selective incorporation and removal of N ‐acyl protecting groups have also been achieved by enzymatic methods (Prasad & Wengel, ).…”

Naphthaloyl group: a new selective amino protecting group for deoxynucleosides in oligonucleotide synthesis

“…After separation, quantification was made at mL) were added triethylamine (0.2 mL) and succinic anhydride (0.55 260 nrn on the basis of peak areas and extinction coefficients of the mrnol). The reaction mixture was worked up as usual (14) to give the nucleosides (Ez6, : dT, 8800; dC, 7300; dA, 15 400; and dG, 1 1 700). final product.…”

“…Synthesis, deprotection, and purification of the tetrarners were carried out by the usual procedure ( 14) (Fig. 1).…”