Design and Synthesis of LNA-Based Mercaptoacetamido-Linked Nucleoside Dimers |
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Authors: | Vivek K Sharma Sunil K Singh Kapil Bohra Chandra Shekhar Reddy L Vinod Khatri Carl E Olsen |
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Institution: | 1. Bioorganic Laboratory, Department of Chemistry , University of Delhi , Delhi , India;2. Faculty of Life Sciences, Department of Natural Sciences , University of Copenhagen , Frederiksberg , Denmark |
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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. |
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Keywords: | Locked nucleic acid phosphate backbone modification mercaptoace- tamido-linkage phosphoramidite-derivative |
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