(R)-2,4-Dihydroxybutyramide seco-Pseudonucleosides:  New Versatile Homochiral Synthons for Synthesis of Modified Oligonucleotides

Abstract

Two series of seco-pseudonucleoside synthons were synthesized from (R)-(+)-r-hydroxy-γ-butyrolactone and (R)-(−)-pantolactone by aminolysis, side-chain protection, dimethoxytritylation, and phosphitylation or solid-phase attachment. The phosphoramidites and solid supports were used in automated DNA synthesis to prepare oligonucleotides modified with one or more 2,4-dihydroxybutyramide units bearing side-chain reporter groups. These new oligonucleotide modification reagents allow the introduction of a label into any desired position within an oligonucleotide chain during solid-phase assembly.Synthetic nonisotopically labeled oligonucleotide probes have found widespread application in molecular biology and various nucleic acids-based assays in medicine. 1 The most expeditious way to obtain these materials is machine-assisted solid-phase synthesis. Despite significant progress made over the last two decades in the area of oligonucleotide technology, 2 there is still a need to develop new modified reagents for oligonucleotide labeling during solid-phase assembly, which may allow introduction of various reporter groups into any predetermined position of a nucleic acid chain.A number of nonnucleoside reagents have been suggested to allow site-specific incorporation of various functional groups and nonradioactive labels into an oligonucleotide chain during solid-phase synthesis. [4][5][6][7][8][9][10][11] Frequently, the precursors were shaped to be spatial surrogates of nucleo-

Efficient stabilization of oligonucleotide duplexes through terpyridine metal complexes

“…To allow structural studies, we chose to use a pantolactone-based ribose mimic developed by Dioubankova et al (2). This synthetic route was used to extend our studies on metal-assisted hybridization of oligonucleotides, providing an easy way to increase nucleic acid duplex stability.…”

Enantioselective Synthesis of Functionalized Quaternary Stereocenters

“…α,γ‐Dihydroxy acids and amides such as 27 and 28 are precursors of β,β‐disubstituted γ‐butyrolactones that are analogs of pantolactone 14. Such lactones provide synthetic pantothenamides ( N ‐modified α,γ‐dihydroxy amides) by aminolysis 15. Recent studies16 have shown that the biological activity of pantothenamides depends on the substitution at, and the configuration of, the quaternary carbon atom.…”

Design and Properties of Ligand-Conjugated Guanine Oligonucleotides for Recovery of Mutated G-Quadruplexes

“…CPG supports for solid-phase oligonucleotide synthesis loaded with the corresponding ligand-containing linkers PyS (96.1 µmol/g), PyL (60.1 µmol/g), PEPy (44.1 µmol/g), BPEA (35.0 µmol/g), and Per (29.9 µmol/g) were obtained according to guidelines in the literature [24]. The PyS linker (N-(1-pyrenemethyl)-( S )-2,4-dihydroxybutyramide) was synthesized as described previously [17,25]. The PyL linker was prepared as described in reference [18].…”