Design and synthesis of LNA-based mercaptoacetamido-linked nucleoside dimers

TY - JOUR

T1 - Design and synthesis of LNA-based mercaptoacetamido-linked nucleoside dimers

AU - Sharma, Vivek K.

AU - Singh, Sunil K.

AU - Bohra, Kapil

AU - Reddy L., Chandra Shekhar

AU - Khatri, Vinod

AU - Olsen, Carl Erik

AU - Prasad, Ashok K.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Three LNA-based mercaptoacetamido-linked nonionic nucleoside dimers T L-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)(-OCH2CH 2CN)-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.

AB - Three LNA-based mercaptoacetamido-linked nonionic nucleoside dimers T L-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)(-OCH2CH 2CN)-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.

U2 - 10.1080/15257770.2013.783218

DO - 10.1080/15257770.2013.783218

M3 - Journal article

C2 - 23581718

SN - 1525-7770

VL - 32

SP - 256

EP - 272

JO - Nucleosides, Nucleotides and Nucleic Acids

JF - Nucleosides, Nucleotides and Nucleic Acids

IS - 5

ER -