DMTr group

This substantial group was developed as a fluorescent, acid-labile protective group for oligonucleotide synthesis. It has properties very similar to those of the DMTr group except that it can be detected down to 10 M on TLC plates with 360-nm ultraviolet light. 

The DMTr group was selectively introduced into a biotin derivative 0 0... 

The Cee group is stable under the acidic conditions used to cleave the DMTr group. ... 

Selective cleavage of the DMTr group from oxygen is accomplished with 80% aq. AcOH (rt, 10 min), whereas selective cleavage of the DMTr group from the thiol is effected with AgN03/NaOAc buffer (rt, 1 min). ... 

The phosphitylation reaction (step a) and sulfurization leading to the corresponding thiophosphate (step b) proceeded under standard conditions. After deprotection (step c) and selective introduction of the DMTr group (step d) no transphosphorylation 2 3 was noted. This fact can be explained by the steric factor combined with the lower activity of thiophos-phates in comparison with normal phosphates. This enabled further phosphitylation (step e) by the customary phosphoroamidites. A difficulty in Se-kine s procedure is that the phosphitylating reagent must be prepared in situ and has relatively low purity. Luckily the by-products formed are inert tetra-coordinate species. 

The overall approach for the synthesis of 3 -0-DMTr derivatives has been carried using these benzoyl derivatives as starting materiaL Introduction of the DMTr group at the 3 -hydroxyl position is accomplished by treatment of 5 -0-benzoyl-2 -deoxynudeosides with DMTrCl in pyridine at 70 °C. The choice of this high reaction temperature furnished an improved reaction rate and better overall yield. Next, treatment with sodium methoxide in MeOH at 0°C removed the 5 -0-benzoyl group [23]. Under these conditions, 3 -0-DMTr-thymidine is isolated in a 90% yield after chromatography (Scheme 10.7). 

The addition of pyrrole as a cation scavenging agent has been recommended for use in deprotection during solid-phase DNA and RNA synthesis. The Px or Tx groups have been recommended as a better alternative to DMTr group in DNA and RNA synthesis because of their faster cleavage rates. 

Recently, a polymer-bound DMTr group has been applied by Mihaichuk et al. [124c] for the 5 -to-3 synthesis on PS using either phosphoramidite or H-phosphonate chemistry. 

However, the Japanese group has noted partial cleavage of the diisopropylsi-lanediyl linkage under the acidic conditions needed for the DMTr group removal [245, 247]. To circumvent this nuisance, Kobori et al. [247] have prepared a highly cross-linked polystyrene-supported phenyldiisopropylsilyl ether linker that proved to be completely stable to detritylation and used it successfully for oligonucleotide synthesis without N-protection by O-selective phosphoramidite chemistry [246] and pyrophosphate formation on solid phase [248]. The anchor can be cleaved under almost neutral conditions by 1M TBAF-AcOH in THF (90% release after 1 h) or 0.2 M triethylamine trihydrofluoride in the presence of 0.4 M triethylamine for 4h. 

Oxazaphospholidines of type 140 have been advocated as alternatives to the more normal phosphoramidite units used in solid-phase synthesis. The unit 141, as an isomeric mixture, has been developed as an all-purpose adaptor for synthesis of oligonucleotides on any of the commercial supports. The unit 141 is attached to the support through 0-5. After removal of the Dmtr group, the first nucleoside is attached via a 2 (3 )-3 link using a phosphoramidite. The desired oligonucleotide is then conventionally assembled, and disconnected by removal of the 0-benzoyl group from the adaptor, which is followed by cyclic phospho-diester formation. ... 

Since the siloxane-bridged oligonucleotide analogs exhibit considerable sensitivity to acid, removal of the DMTr group was effected with ZnBr2 or brief treatment with 3% trichloro acetic acid. Short hydrazine treatment (0.5M hydrazine hydrate in pyridine acetic acid [3 2]... 

The formacetal linkage has been reported to be stable against moderate acid treatment (80% acetic acid for 3 h at 45°C), allowing removal of the DMTr group without additional problems. Treatment of a meth-... 

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