800387-68-2Relevant academic research and scientific papers
Synthesis of a 1′-aminomethylthymidine and oligodeoxyribonucleotides with 1′-acylamidomethylthymidine residues
Gruenefeld, Peter,Richert, Clemens
, p. 7543 - 7551 (2007/10/03)
Reported here is a 10-step synthesis of a phosphoramidite building block of 1′-aminomethylthymidine that starts from 2-deoxyribose. The framework of the branched aminonucleoside was elaborated from a known 1-cyano-1-bromo glycosyl donor, whose reaction with the silylated nucleobase furnished the 1′-cyanide, which was reduced to the desired aminomethylnucleoside. The N-allyloxycarbonyl (Alloc)-protected nucleoside was converted to a phosphoramidite building block and incorporated into the oligonucleotides 5′-GCAT*TATTAC-3′, and 5′-GCAT*TAT*TAC- 3′, where T* denotes 1′-acylamidomethylthymidine residues. Removal of the Alloc protecting group and acylation with the residue of pyrene-1-yl-butanoic acid were achieved on support, using microwave irradiation to ensure full conversion. The UV-melting point of the duplex of the singly and doubly modified decamers with their fully complementary target sequence is 0.1-6.9 °C higher than that of the unmodified control duplex, depending on the salt concentration. This suggests that the aminomethyl linker may allow for the placing of a functional "payload" in the minor groove of DNA duplexes without disrupting the helix. Oligonucleotides thus endowed with functional modifications may become useful for biomedical applications.
