Applications of Mechanochemistry for the Synthesis of DNA on Ionic Liquid Supports

Johnston, Christopher; Hardacre, Christopher; Migaud, Marie E.

doi:10.1002/cmtd.202100002

Cited by 5 publications

(3 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, while the challenges of achieving good isolated yields following chromatography purifications still remain, we observed that conditions where nucleosides and nucleotides could be exhaustively dried offered better outcomes. We had made similar observations when handling P(III) reagents with nucleosides [ 43 , 44 ]. Yet, when we applied this synthetic approach to isotopically labeled NAD nucleoside precursors, we were able to generate an NAD isotopologue in good isolated yields; in quantities that would be well suited to inform on exogenous NAD turn-over, including NAD’s use by sirtuins, PARP enzymes, glycohydrolases, as well as reductases, in cell based-assays by mass spectrometry.…”

Section: Resultsmentioning

confidence: 82%

Synthesis of Mixed Dinucleotides by Mechanochemistry

et al. 2022

Self Cite

View full text Add to dashboard Cite

We report the synthesis of vitamin B1, B2, and B3 derived nucleotides and dinucleotides generated either through mechanochemical or solution phase chemistry. Under the explored conditions, adenosine and thiamine proved to be particularly amenable to milling conditions. Following optimization of the chemistry related to the formation pyrophosphate bonds, mixed dinucleotides of adenine and thiamine (vitamin B1), riboflavin (vitamin B2), nicotinamide riboside and 3-carboxamide 4-pyridone riboside (both vitamin B3 derivatives) were generated in good yields. Furthermore, we report an efficient synthesis of the MW+4 isotopologue of NAD+ for which deuterium incorporation is present on either side of the dinucleotidic linkage, poised for isotopic tracing experiments by mass spectrometry. Many of these mixed species are novel and present unexplored possibilities to simultaneously enhance or modulate cofactor transporters and enzymes of independent biosynthetic pathways.

show abstract

Section: Resultsmentioning

confidence: 82%

Synthesis of Mixed Dinucleotides by Mechanochemistry

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…In order to reduce solvent usage, in 2021 Migaud and co-workers demonstrated the concept of using an ionic liquid support in combination with liquid-assisted mechanochemistry for various aspects of oligonucleotide synthesis (Scheme 29 ). 125…”

Section: Salient Developments In the Mechanochemical Activation Of Sy...mentioning

confidence: 99%

Salient Achievements in Synthetic Organic Chemistry Enabled by Mechanochemical Activation

Juaristi

Avila‐Ortiz

2023

Synthesis

View full text Add to dashboard Cite

Although known for millenia, it is only recently that mechanochemistry has caught serious attention by many chemists. Indeed, during the past 15 years an extraordinary number of reports concerning solid-state chemical transformations through grinding and milling techniques has been recorded. This short review discusses the circumstances that led to such renaissance, highlighting the present intense interest in so-called green chemistry, the enabling capacity of mechanochemistry to handle insoluble substrates, and the finding of the profound influence that additives can have on mechanochemically activated reactions. The core of this account focuses on salient developments in synthetic organic chemistry, especially in amino acid and peptide mechanosynthesis, the successful employment of mechanochemical activation in combination with asymmetric organocatalysis, the promising combination of mechanochemical activation with enzymatic and whole cell biocatalysis, and the remarkable achievement of multicomponent selective reactions via complex, multistep reaction pathways. The final section is dedicated to comment on some pending tasks in the area, such as scaling-up of milling processes to be of practical use in the chemical industry, the requirement of easier and more efficient control of reaction parameters and monitoring devices, and consequently the careful analysis of additional procedures for a proper understanding of mechanochemical phenomena.

show abstract

“…In order to overcome this issue, we turned to mechanochemistry. Protocols in which reagents are subjected to intimate mixing and grinding using ball mills have become increasingly popular in recent years, affording reaction products that cannot be obtained using traditional solution-based methods. − Additionally, the use of mechanochemistry obviates the need for solvent and can give short reaction times, good scalability, and even opportunities for in situ reaction monitoring. , Mechanochemical P-centered nucleophilic substitution has been applied to build P–O(N) bonds in small molecules − and functional polymers. , …”

mentioning

confidence: 99%

Sustainable Production of Reduced Phosphorus Compounds: Mechanochemical Hydride Phosphorylation Using Condensed Phosphates as a Route to Phosphite

et al. 2022

View full text Add to dashboard Cite

In pursuit of a more sustainable production of phosphorous acid (H 3 PO 3 ), a versatile chemical with phosphorus in the +3 oxidation state, we herein report that condensed phosphates can be employed to phosphorylate hydride reagents under solvent-free mechanochemical conditions to furnish phosphite (HPO 3 2– ). Using potassium hydride as the hydride source, sodium trimetaphosphate (Na 3 P 3 O 9 ), triphosphate (Na 5 P 3 O 10 ), pyrophosphate (Na 4 P 2 O 7 ), fluorophosphate (Na 2 PO 3 F), and polyphosphate (“(NaPO 3 ) n ”) engendered phosphite in optimized yields of 44, 58, 44, 84, and 55% based on total P content, respectively. Formation of overreduced products including hypophosphite (H 2 PO 2 – ) was identified as a competing process, and mechanistic investigations revealed that hydride attack on in-situ-generated phosphorylated phosphite species is a potent pathway for overreduction. The phosphite generated from our method was easily isolated in the form of barium phosphite, a useful intermediate for production of phosphorous acid. This method circumvents the need to pass through white phosphorus (P 4 ) as a high-energy intermediate and mitigates involvement of environmentally hazardous chemicals. A bioproduced polyphosphate was found to be a viable starting material for the production of phosphite. These results demonstrate the possibility of accessing reduced phosphorus compounds in a more sustainable manner and, more importantly, a means to close the modern phosphorus cycle.

show abstract

Applications of Mechanochemistry for the Synthesis of DNA on Ionic Liquid Supports

Cited by 5 publications

References 36 publications

Synthesis of Mixed Dinucleotides by Mechanochemistry

Synthesis of Mixed Dinucleotides by Mechanochemistry

Salient Achievements in Synthetic Organic Chemistry Enabled by Mechanochemical Activation

Sustainable Production of Reduced Phosphorus Compounds: Mechanochemical Hydride Phosphorylation Using Condensed Phosphates as a Route to Phosphite

Contact Info

Product

Resources

About