Solid-phase synthesis of P-boronated oligonucleotides by the H-boranophosphonate method.
Sho Uehara1, Shingo Hiura, Renpei Higashida
1Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo , Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan .
The Journal of Organic Chemistry
|April 1, 2014
Summary
Researchers developed a novel H-boranophosphonate oligonucleotide. This versatile precursor can be used to create various P-boronated oligonucleotides, including those with enhanced affinity for therapeutic applications.
Area of Science:
- Oligonucleotide Chemistry
- Medicinal Chemistry
- Biotechnology
Background:
- P-boronated oligonucleotides are gaining attention as potential therapeutic agents.
- Developing versatile precursors for novel oligonucleotide analogs is crucial for advancing nucleic acid therapeutics.
Purpose of the Study:
- To develop a novel H-boranophosphonate oligonucleotide.
- To demonstrate its utility as a versatile precursor for various P-boronated oligonucleotides.
- To synthesize and evaluate a locked nucleic acid-modified boranophosphate oligonucleotide.
Main Methods:
- Synthesis of H-boranophosphonate oligonucleotide.
- Conversion of the precursor to boranophosphate, boranophosphorothioate, and boranophosphoramidate derivatives.
- Synthesis of locked nucleic acid-modified boranophosphate oligonucleotide.
Main Results:
- Successfully developed H-boranophosphonate oligonucleotide.
- Demonstrated its versatility as a precursor for multiple P-boronated oligonucleotide types.
- Synthesized a locked nucleic acid-modified boranophosphate oligonucleotide with significantly improved binding affinity.
Conclusions:
- H-boranophosphonate oligonucleotides serve as versatile precursors for diverse P-boronated oligonucleotide synthesis.
- This approach enables the creation of modified oligonucleotides with enhanced properties, such as increased affinity.
- The developed method holds promise for the advancement of oligonucleotide-based therapeutics.
More Related Videos
08:46Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides
Published on: July 26, 2018
8.2K
08:46Preparation and Reactivity of a Triphosphenium Bromide Salt: A Convenient and Stable Source of PhosphorusI
Published on: November 22, 2016
7.3K
Related Concept Videos
03:08Hydroboration-Oxidation of Alkenes
10.1K
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
10.1K
02:36Regioselectivity and Stereochemistry of Hydroboration
7.8K
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn...
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn...
7.8K
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
19.8K
Introduction
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
19.8K
00:57Cationic Chain-Growth Polymerization: Mechanism
2.1K
The cationic polymerization mechanism consists of three steps: initiation, propagation, and termination. In the initiation step of the polymerization process, the π bond of a monomer gets protonated by the Lewis acid catalyst, which is formed from boron trifluoride and water. The protonation of the π bond generates a carbocation stabilized by the electron‐donating group. In the propagation step, the π bond of the second monomer acts as a nucleophile and attacks the...
2.1K
01:01Phosphodiester Linkages
99.1K
Overview
Phosphodiester bond forms when a phosphoric acid molecule (H3PO4) links with two hydroxyl groups (–OH) of two other molecules, forming two ester bonds. Two water molecules are released in this process. The phosphodiester bond is commonly found in nucleic acids (DNA and RNA) and plays a critical role in their structure and function.
Phosphodiester Bonds Link Nucleotides Together
DNA and RNA are polynucleotides or long chains of nucleotides that are linked together. A nucleotide is...
Phosphodiester bond forms when a phosphoric acid molecule (H3PO4) links with two hydroxyl groups (–OH) of two other molecules, forming two ester bonds. Two water molecules are released in this process. The phosphodiester bond is commonly found in nucleic acids (DNA and RNA) and plays a critical role in their structure and function.
Phosphodiester Bonds Link Nucleotides Together
DNA and RNA are polynucleotides or long chains of nucleotides that are linked together. A nucleotide is...
99.1K
03:24Hybridization of Atomic Orbitals I
51.7K
The mathematical expression known as the wave function, ψ, contains information about each orbital and the wavelike properties of electrons in an isolated atom. When atoms are bound together in a molecule, the wave functions combine to produce new mathematical descriptions that have different shapes. This process of combining the wave functions for atomic orbitals is called hybridization and is mathematically accomplished by the linear combination of atomic orbitals. The new orbitals that...
51.7K