Open AccessSensitive Oligodeoxynucleotide Synthesis Using Dim and Dmoc as Protecting Groups
Author(s) -
Shahien Shahsavari,
Dhananjani N. A. M. Eriyagama,
Jinsen Chen,
Bhaskar Halami,
Yipeng Yin,
Komal Chillar,
Shiyue Fang
Publication year - 2019
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.9b01527
Subject(s) - chemistry , nucleophile , amine gas treating , phosphate , protecting group , alkyl , combinatorial chemistry , chloride , solid phase synthesis , organic chemistry , catalysis , biochemistry , peptide
In traditional oligodeoxynucleotide (ODN) synthesis, phosphate groups are protected with the 2-cyanoethyl group, and amino groups are protected with acyl groups. At the end of ODN synthesis, deprotection is achieved with strong bases and nucleophiles. Therefore, traditional technologies are not suitable for the synthesis of ODNs containing sensitive functionalities. To address the problem, we report the use of Dim and Dmoc groups, which are based on the 1,3-dithian-2-yl-methyl function, for phosphate and amine protection for the solid phase ODN synthesis. Using the new Dim-Dmoc protection, deprotection was achieved under mild oxidative conditions without using any strong bases and nucleophiles. As a result, the new technology is suitable for the synthesis of ODNs containing sensitive functions. To demonstrate feasibility, seven 20-mer ODNs including four that contain sensitive ester and alkyl chloride groups were synthesized, purified with RP HPLC, and characterized with MALDI-TOF MS and enzyme digestion essays. High purity ODNs were obtained.