Design and Synthesis of LNA-Based Mercaptoacetamido-Linked Nucleoside Dimers

Abstract

Three LNA-based mercaptoacetamido-linked nonionic nucleoside dimers TL-S-T, T-S-TL , and TL-S-TL have been synthesized by HOBT and HBTU catalyzed condensation of silyl-protected 2-S-(thymidin-5 ′-yl)mercaptoacetic acid or 2-S-(2 ′-O,4 ′-C-methylenethymidin-5 ′-yl)mercaptoacetic acid with 3 ′-amino-3 ′-deoxy-5 ′-O-DMT-2 ′-O,4 ′-C-methylenethymidine or with 3 ′-amino-3 ′-deoxy-5 ′-O-DMT-β-thymidine followed by desilylation of the protected dimers. The 3 ′-O-phosphoramidite derivative of one of the nucleoside dimers was successfully prepared by condensation with [P(-Cl)(-OCH2CH2CN)-N(iPr)2}] in DCM in the presence of N,N-diisopropylethylamine (DIPEA), which is a building block for the preparation of mercaptoacetamido-linked oligonucleotides of therapeutic applications.