Access to 1′-Amino Carbocyclic Phosphoramidite to Enable Postsynthetic Functionalization of Oligonucleotides

Rydzik, Anna M.; Balk, Regina C.; Koegler, Martin; Steinle, Tobias; Riether, Doris; Gottschling, Dirk

doi:10.1021/acs.orglett.1c02302

Cited by 3 publications

(3 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another approach involves an aminocyclopenta(e)ne, synthesized from (±)-2-azabicyclo[2.2.1]hept-5-en-3-one, also known as the Vince lactam . The racemic lactam can readily be converted to the optically pure intermediate, which has the same configuration as the carbocyclic nucleosides, through enzymatic resolution, and this intermediate can serve as the precursor for various carbocyclic nucleosides …”

mentioning

confidence: 99%

“…19 The racemic lactam can readily be converted to the optically pure intermediate, which has the same configuration as the carbocyclic nucleosides, through enzymatic resolution, 20 and this intermediate can serve as the precursor for various carbocyclic nucleosides. 21 As depicted in Scheme 1, the synthesis of car-RNA uridine started from aminocyclopentene 7. 19,22 The olefin 7 was coupled with 3-methoxyacryloyl isocyanate, prepared in situ from 3-methoxyacrylic acid, and cyclized under acidic conditions to afford uridine derivative 8 as described.…”

mentioning

confidence: 99%

See 1 more Smart Citation

RNAs Containing Carbocyclic Ribonucleotides

et al. 2021

View full text Add to dashboard Cite

Toward the goal of evaluation of carbocyclic ribonucleoside-containing oligonucleotide therapeutics, we developed convenient, scalable syntheses of all four carbocyclic ribonucleotide phosphoramidites and the uridine solid-support building block. Crystallographic analysis confirmed configuration and stereochemistry of these building blocks. Duplexes with carbocyclic RNA (car-RNA) modifications in one strand were less thermodynamically stable than duplexes with unmodified RNA. However, circular dichroism spectroscopy indicated that global conformations of the duplexes containing car-RNAs were similar to those in the unmodified duplexes.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

RNAs Containing Carbocyclic Ribonucleotides

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The Fmoc group is a commonly used amine protecting group, especially in peptide synthesis, and it is readily removable by treatment with a weak base, such as 20% piperidine in DMF [ 28 , 29 , 30 ]. Moreover, phosphoramidites bearing an Fmoc-protected amino group have been used for oligonucleotide synthesis [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Therefore, we designed Fmoc-based phosphoramidite reagents ( Figure 1 B) and applied them to oligonucleotide synthesis.…”

Section: Introductionmentioning

confidence: 99%

Development of Phosphoramidite Reagents for the Synthesis of Base-Labile Oligonucleotides Modified with a Linear Aminoalkyl and Amino-PEG Linker at the 3′-End

2022

View full text Add to dashboard Cite

Oligonucleotides with an amino linker at the 3′-end are useful for the preparation of conjugated oligonucleotides. However, chemically modified nucleosides, which are unstable under basic conditions, cannot be incorporated into oligonucleotides using the conventional method entailing the preparation of oligonucleotides bearing a 3′-amino linker. Therefore, we designed Fmoc-protected phosphoramidites for the synthesis of base-labile oligonucleotides modified with a 3′-amino linker. The resultant phosphoramidites were then successfully incorporated into oligonucleotides bearing a 3′-amino linker. Various basic solutions were investigated for protecting group removal. All the protecting groups were removed by treating the oligonucleotides with 40% aqueous methylamine at room temperature for 2 h. Thus, the deprotection time and temperature were significantly reduced compared to the conventional conditions (28% NH3 aq., 55 °C, 17 h). In addition, the oligonucleotide protecting groups could be removed using a mild base (e.g., 50 mM potassium carbonate methanol solution). Furthermore, base-labile oligonucleotides bearing an amino linker at the 3′-end were successfully synthesized using the developed phosphoramidite reagents, highlighting the utility of our strategy.

show abstract

Nicotinamide Riboside: What It Takes to Incorporate It into RNA

Wenzek,

Biallas,

Müller

2024

Molecules

View full text Add to dashboard Cite

Nicotinamide is an important functional compound and, in the form of nicotinamide adenine dinucleotide (NAD), is used as a co-factor by protein-based enzymes to catalyze redox reactions. In the context of the RNA world hypothesis, it is therefore reasonable to assume that ancestral ribozymes could have used co-factors such as NAD or its simpler analog nicotinamide riboside (NAR) to catalyze redox reactions. The only described example of such an engineered ribozyme uses a nicotinamide moiety bound to the ribozyme through non-covalent interactions. Covalent attachment of NAR to RNA could be advantageous, but the demonstration of such scenarios to date has suffered from the chemical instability of both NAR and its reduced form, NARH, making their use in oligonucleotide synthesis less straightforward. Here, we review the literature describing the chemical properties of the oxidized and reduced species of NAR, their synthesis, and previous attempts to incorporate either species into RNA. We discuss how to overcome the stability problem and succeed in generating RNA structures incorporating NAR.

show abstract

Access to 1′-Amino Carbocyclic Phosphoramidite to Enable Postsynthetic Functionalization of Oligonucleotides

Cited by 3 publications

References 22 publications

RNAs Containing Carbocyclic Ribonucleotides

RNAs Containing Carbocyclic Ribonucleotides

Development of Phosphoramidite Reagents for the Synthesis of Base-Labile Oligonucleotides Modified with a Linear Aminoalkyl and Amino-PEG Linker at the 3′-End

Nicotinamide Riboside: What It Takes to Incorporate It into RNA

Contact Info

Product

Resources

About