5'-Methyl-DNA-A New Oligonucleotide Analog: Synthesis and Biochemical Properties

Abstract

Analogs of antisense or antigene oligodeoxyribonucleotides are of interest as potential antiviral, antibacterial, and anticancer agents.1-4 Much recent research has shown that though the selective modulation of gene expression is certainly feasible, the exact mechanistic role of interfering oligonucleotides remains uncertain.5-7 Both research and potential therapeutic applications, however,

Synthesis of (5′S)-5′-C-Alkyl-2′-deoxynucleosides

“…Although via this kinetic resolution, 2a (5'S) and 2b (5'S) were obtained in acceptable diastereoisomer purity, we generally preferred to separate the diastereomer mixture of 4a and 4b by flash chromatography (FC) before reduction. Therefore, 2a(5'S)-and 2b (5'S) were usually prepared from the diastereoisomerically pure (5'S,6'R)-4a and -4b 3 ) in 84 and 68% yield, respectively. Desilylation of 2a (5'S) to 5a was achieved in 95% yield with Bu 4 NF.…”

“…As the main by-product in all experiments, the reduced 3'-O-[(tert-butyl)dimethylsilyl]thymidine was obtained, most likely as a result of a b-hydride transfer [10] of the Grignard reagent to the carbonyl Catom. Also the change of the organometallic reagent to BuCeCl 2 [11] or BuTi(O i Pr) 3 did not improve the yield or the diastereoselectivity (Entries 5 and 6). The failure in this direct approach prompted us to change strategy.…”

“…The synthesis of the 5'-C-methyl-substituted deoxyribonucleosides, the simplest members of this class, via deoxygenation of the corresponding hexofuranose nucleosides thereby pioneered the field [1]. More recent and more general approaches involve the use of the corresponding nucleosid-5'-al (CH 2 (5')OH replaced by CH(5')O) as starting materials, to which the 5'-C-substituents were added either via organometallic reagents [2] [3] or via aldol-type chemistry [4] [5]. A radical approach has been used to prepare 5'-C-allylated nucleosides starting from 5'-selenonucleosides [6].…”

Surface modification and in vitro blood compatibilities of polyurethanes containing z‐lysine segments in the main chain

“…Concerning the thermal stability of the resulting duplexes, a penalty is paid in all cases, probably due to a combination of slight sterical disturbance and a distortion of the duplex hydration. Small 5′‐ C ‐substituents, like methyl, hydroxymethyl and others, have earlier demonstrated relatively small but unavoidable decreases in duplex stabilities (Δ T m values of 1 – 3 °C for each incorporation),21–23 and these thermal penalties seem to increase with the sterical bulk of the substituent. Leumann and co‐workers inserted hydrophobic butyl and isopentyl substituents and observed decreases of around 2 – 3 °C 24.…”

Synthesis and Incorporation of C(5′)‐Ethynylated Uracil‐Derived Phosphoramidites into RNA.

“…Their availability leads to the question about the influence of the ethynyl substituents at C(5') on the conformation and pairing of RNA analogues derived from these monomers (Fig. Only a few nucleosides modified at C(5') 2 ) were incorporated into RNA or DNA, and had either little effect on duplex stability [35] [36] or destabilized it [18] [37] [38] (compare [28] [39] [40]). Information about the influence of substituents at C(5') in DNA and RNA analogues on pairing is of interest in the context of antisense or antigene therapy [5 ± 14] and in view of preparing RNA analogues possessing new functional properties [15 ± 18].…”