Oligonucleotide synthesis under mild deprotection conditions

Chillar, Komal; Eriyagama, Dhananjani; Yin, Yipeng; Shahsavari, Shahien; Halami, Bhaskar; Apostle, Alexander; Fang, Shiyue

doi:10.1039/d2nj03845e

Cited by 3 publications

(13 citation statements)

References 23 publications

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“…The meDmoc group was chosen over Dmoc because its deprotection does not need a scavenger. 8 c ,9 All the syntheses were planned to be carried out using linker 3 , which allows ODN cleavage under the same non-nucleophilic conditions for Dmoc deprotection. Thus, the plan required monomers 1a–c , 2a–c and linker 3 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The synthesis of 2a–c and 3 has been reported earlier. 7,9 For the synthesis of 1a–c , the PEGylation agent 4 was needed (Scheme 1). Commercial 5 was reacted with HO(PEG) 4 OMe ( 6 ) to give 7 , which upon treating with an acid gave 8 .…”

Section: Resultsmentioning

confidence: 99%

“…For the synthesis of 1a (Scheme 2), cytidine nucleoside derivative 11 9 was treated with 2 equivalents LDA and 1 equivalent 4 to give the pDmoc protected dC 12 . This condition for the introduction of carbamate groups to arylamines was known.…”

Section: Resultsmentioning

confidence: 99%

“…11 The pDmoc dA phosphoramidite 1b was synthesized under similar conditions. For the synthesis of pDmoc dG phosphoramidite 1c , the procedure was similar except that 21 , of which the lactam of the nucleobase was protected with a TBDPS group, 9 was used as the starting material. Good to excellent yields were obtained for the steps for the synthesis of 1a–b .…”

Section: Resultsmentioning

confidence: 99%

“…8 However, the longest ODN that could be synthesized is a 23-mer. 9 In this paper, we report the use of PEGylated Dmoc (pDmoc) phosphoramidites for sensitive ODN synthesis. Our hypothesis was that the limited length of ODNs that could be synthesized using the Dmoc methods was due to the hydrophobicity of the Dmoc group.…”

Section: Introductionmentioning

confidence: 99%

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PEGylated Dmoc phosphoramidites for sensitive oligodeoxynucleotide synthesis

Chillar,

Yin,

Apostle

et al. 2023

Org. Biomol. Chem.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PEGylated Dmoc phosphoramidites for sensitive oligodeoxynucleotide synthesis

Chillar,

Yin,

Apostle

et al. 2023

Org. Biomol. Chem.

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Oligodeoxynucleotide Synthesis Under Non‐Nucleophilic Deprotection Conditions

Fang,

Chillar,

Yin

et al. 2024

Current Protocols

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This protocol describes a method for the incorporation of sensitive functional groups into oligodeoxynucleotides (ODNs). The nucleophile‐sensitive epigenetic N4‐acetyldeoxycytosine (4acC) DNA modification is used as an example, but other sensitive groups can also be incorporated, e.g., alkyl halide, α‐haloamide, alkyl ester, aryl ester, thioester, and chloropurine groups, all of which are unstable under the basic and nucleophilic deprotection and cleavage conditions used in standard ODN synthesis methods. The method uses a 1,3‐dithian‐2‐yl‐methoxycarbonyl (Dmoc) group that carries a methyl group at the carbon of the methoxy moiety (meDmoc) for the protection of exo‐amines of nucleobases. The growing ODN is anchored to a solid support via a Dmoc linker. With these protecting and linking strategies, ODN deprotection and cleavage are achieved without using any strong bases and nucleophiles. Instead, they can be carried out under nearly neutral non‐nucleophilic oxidative conditions. To increase the length of ODNs that can be synthesized using the meDmoc method, the protocol also describes the synthesis of a PEGylated Dmoc (pDmoc) phosphoramidite. With some of the nucleotides being incorporated with pDmoc‐CE phosphoramidite, the growing ODN on the solid support carries PEG moieties and becomes more soluble, thus enabling longer ODN synthesis. The ODN synthesis method described in this protocol is expected to make many sensitive ODNs that are difficult to synthesize accessible to researchers in multiple areas, such as epigenetics, nanopore sequencing, nucleic acid‐protein interactions, antisense drug development, DNA alkylation carcinogenesis, and DNA nanotechnology. © 2024 Wiley Periodicals LLC.Basic Protocol: Sensitive ODN synthesisSupport Protocol 1: Synthesis of meDmoc‐CE phosphoramiditesSupport Protocol 2: Synthesis of a pDmoc‐CE phosphoramidite

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Trendbericht Organische Chemie 2024

Breugst,

Andexer,

Barra

et al. 2024

Nachr Chem

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Unter anderem das hat die Organik im letzten Jahr bewegt: milde Oxidation mit Elektrochemie, Oxidation zu enantiomerenreinen Sulfonylverbindungen, Flüssigkristallphasen erkennen mit maschinellem Lernen, CO2 reagiert zu Succinat und Carbamaten, eine Alternative zu Bisphenol A, Subporphyrine, photoschaltbare Spinmaterialien, photochemische Thiophen‐Ringerweiterung, und Peptide werden mit Bor versehen und cyclisiert. Die Zusammenstellung des Trendberichts koordiniert hat Martin Breugst, Universität Chemnitz.

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Oligonucleotide synthesis under mild deprotection conditions

Abstract: Over a hundred non-canonical nucleotides have been found in DNA and RNA. Many of them are sensitive toward nucleophiles. Because known oligonucleotide synthesis technologies require nucleophilic conditions for deprotection, currently...

Cited by 3 publications

References 23 publications

PEGylated Dmoc phosphoramidites for sensitive oligodeoxynucleotide synthesis

PEGylated Dmoc phosphoramidites for sensitive oligodeoxynucleotide synthesis

Oligodeoxynucleotide Synthesis Under Non‐Nucleophilic Deprotection Conditions

Trendbericht Organische Chemie 2024

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