We synthesized a three-way branched oligodeoxynucleotide (ODN) 30-mer using a new branch unit with acid-labile DMTr and oxidatively cleavable TrS groups as orthogonal protecting groups. The branched ODN was successfully synthesized using 5-[3,5-bis(trifluoromethyl)phenyl]-1H-tetrazole and (2R,8aS)-(+)-(camphorylsulfonyl)oxaziridine as the activator of phosphoramidite units and the oxidizing reagent, respectively. We also found that the TrS group was orthogonal to the Lev, TBDMS, and Fmoc groups. These results indicate the possibility of the synthesis of more complex four- and five-way branched ODNs by the combined use of DMTr, TrS, Lev, TBDMS, and Fmoc groups.
The new protecting groups 1a,b and 2a,b were developed for the 5'-OH group of deoxynucleosides by utilizing the unique characters of the sulfenate and sulfenamide linkage. These new protecting groups have a 2-(hydroxymethyl)benzoyl or 2-[(methylamino)methyl]benzoyl skeleton whose hydroxy O-atom or amino Natom was blocked with a tritylthio-type substituent. They are removable by intramolecular cyclization following the oxidative hydrolysis of the tritylthio-type substituents under mildly oxidative conditions (Schemes 3 and 6). Among them, 2-{{[(4-methoxytrityl)sulfenyl]oxy}methyl}benzoyl (MOB; 2b) was found to be the most preferable for protection of the 5'-OH function of deoxynucleosides. MOB can be introduced at the 5'-OH groups of various deoxynucleosides without the protection of the 3'-OH functions (Scheme 5). The applicability of the MOB group to a new oligodeoxynucleotide synthesis protocol without acid treatment was demonstrated by the solid-phase synthesis of a tetrathymidylate (Scheme 8).Introduction. ± Oxidatively cleavable protecting groups in place of the acid-labile 4,4'-dimethoxytrityl ((MeO) 2 Tr) group for the 5'-hydroxy function [1] [2] have been developed aiming at new oligonucleotide-synthesis protocols without acid treatment. These new protocols suppress the unfavorable depurination promoted by the acid treatment during the detritylation step in the current DNA synthesis [3 ± 6]. Moreover, if appropriately designed, use of such protecting groups can reduce the chemical steps included in a single-chain-elongation cycle from the conventional four (coupling, capping, oxidation, and detritylation) to three (coupling, capping, and oxidation/ deprotection) steps [1] [2]. To date, there have been reported only two classes of protecting groups that can be used for this strategy. One is phenoxycarbonyl-type protecting groups reported by Caruthers×s group [1], and the other is the (4-methoxytrityl)thio (MeOTrS) group [2] reported by us.We have been interested in the MeOTrS group because of the unique property of the single bond between the O-and divalent S-atom, which are cleavable under mild oxidation conditions such as I 2 solution in H 2 O/pyridine [2] [7]. Moreover, the MeOTrS-protected nucleoside could be converted to the corresponding nucleoside phosphoramidite unit, which was successfully applied to the three-step oligodeoxynucleotide synthesis without acid treatment [2]. The MeOTrS group was superior in this respect to the (2,4-dinitrophenyl)thio [8] [9] group (DNPS) reported previously as a
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