An expanded framework toward improving the detritylation reaction in solid-phase oligonucleotide syntheses - filling
Quanjian Li1, Yogesh S Sanghvi2, Hongbin Yan1
1Department of Chemistry, Brock University, St. Catharines, ON, Canada.
Nucleosides, Nucleotides & Nucleic Acids
|August 9, 2024
Summary
Understanding detritylation reactions in solid-phase oligonucleotide synthesis (SPOS) is crucial. Methanol is reactive but incompatible with acids, impacting deblock solutions for large-scale SPOS.
Area of Science:
- Chemical Synthesis
- Oligonucleotide Chemistry
- Process Optimization
Background:
- Solid-phase oligonucleotide synthesis (SPOS) relies on efficient detritylation.
- Interactions involving solvents, acids, and scavengers can impact reaction efficiency.
- Optimizing detritylation is key for successful large-scale SPOS.
Purpose of the Study:
- To evaluate the reactivity of common trityl cation scavengers.
- To investigate the interaction of scavengers with acids during detritylation.
- To provide insights for optimizing detritylation in SPOS.
Main Methods:
- Utilized a stopped-flow setup for kinetic analysis.
- Screened various scavengers including methanol, thioanisole, and silanes.
- Assessed scavenger reactivity towards tritylium hexafluorophosphate.
Main Results:
- Methanol exhibited the highest reactivity, while thioanisole showed the least.
- Methanol reacts with trichloroacetic acid, precluding its use in pre-mixed deblock solutions.
- Scavenger-acid interactions are a critical consideration.
Conclusions:
- The choice of scavenger and solvent is critical for detritylation efficiency in SPOS.
- Methanol's reactivity with acids necessitates careful handling in deblock solutions.
- Comprehensive consideration of all interactions is vital for optimizing large-scale SPOS.
Related Concept Videos
00:53Olefin Metathesis Polymerization: Acyclic Diene Metathesis (ADMET)
1.9K
Acyclic diene metathesis polymerization or ADMET polymerization involves cross-metathesis of terminal dienes, such as 1,8-nonadiene, to give linear unsaturated polymer and ethylene. As ADMET is a reversible process, the formed ethylene gas must be removed from the reaction mixture to complete the polymerization process.
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
Similar to cross-metathesis, ADMET also involves the formation of metallacyclobutane intermediate by [2+2] cycloaddition of one of the double bonds of a terminal diene with...
1.9K
01:27Aldol Condensation with β-Diesters: Knoevenagel Condensation
3.0K
The Knoevenagel condensation is an aldol-type reaction involving the condensation of aldehydes or ketones with active methylene compounds such as β-diesters to produce substituted olefins.
3.0K
02:44Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
10.0K
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
10.0K
01:38Preparation of Alcohols via Substitution Reactions
5.8K
Overview
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
5.8K
01:24Diels–Alder Reaction: Characteristics of Dienophiles
6.0K
In a Diels–Alder reaction, the diene is usually an electron-rich system and acts as a nucleophile, whereas the dienophile is electron-deficient and functions as an electrophile. Much like the diene, the nature of the dienophile significantly impacts the outcome of the reaction.
Characteristics of Dienophiles
Generally, the best dienophiles are alkenes containing electron-withdrawing substituents such as carbonyl, nitrile, and nitro groups. The feasibility of a Diels–Alder reaction depends...
Characteristics of Dienophiles
Generally, the best dienophiles are alkenes containing electron-withdrawing substituents such as carbonyl, nitrile, and nitro groups. The feasibility of a Diels–Alder reaction depends...
6.0K
02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
5.7K
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
5.7K