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On-demand synthesis of phosphoramidites

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On-demand synthesis of phosphoramidites. / Sandahl, Alexander F.; Nguyen, Thuy J.D.; Hansen, Rikke A. et al.

In: Nature Communications, Vol. 12, 2760, 12.2021.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Vancouver

Sandahl AF, Nguyen TJD, Hansen RA, Johansen MB, Skrydstrup T , Gothelf KV. On-demand synthesis of phosphoramidites. Nature Communications. 2021 Dec;12:2760. doi: 10.1038/s41467-021-22945-z

Author

Sandahl, Alexander F. ; Nguyen, Thuy J.D. ; Hansen, Rikke A. et al. / On-demand synthesis of phosphoramidites. In: Nature Communications. 2021 ; Vol. 12.

Bibtex

@article{ce482dd5d18d4897836e9076398cde24,

title = "On-demand synthesis of phosphoramidites",

abstract = "Automated chemical synthesis of oligonucleotides is of fundamental importance for the production of primers for the polymerase chain reaction (PCR), for oligonucleotide-based drugs, and for numerous other medical and biotechnological applications. The highly optimised automised chemical oligonucleotide synthesis relies upon phosphoramidites as the phosphate precursors and one of the drawbacks of this technology is the poor bench stability of phosphoramidites. Here, we report on the development of an on-demand flow synthesis of phosphoramidites from their corresponding alcohols, which is accomplished with short reaction times, near-quantitative yields and without the need of purification before being submitted directly to automated oligonucleotide synthesis. Sterically hindered as well as redox unstable phosphoramidites are synthesised using this methodology and the subsequent couplings are near-quantitative for all substrates. The vision for this technology is direct integration into DNA synthesisers thereby omitting manual synthesis and storage of phosphoramidites.",

author = "Sandahl, {Alexander F.} and Nguyen, {Thuy J.D.} and Hansen, {Rikke A.} and Johansen, {Martin B.} and Troels Skrydstrup and Gothelf, {Kurt V.}",

year = "2021",

month = dec,

doi = "10.1038/s41467-021-22945-z",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - On-demand synthesis of phosphoramidites

AU - Sandahl, Alexander F.

AU - Nguyen, Thuy J.D.

AU - Hansen, Rikke A.

AU - Johansen, Martin B.

AU - Skrydstrup, Troels

AU - Gothelf, Kurt V.

PY - 2021/12

Y1 - 2021/12

N2 - Automated chemical synthesis of oligonucleotides is of fundamental importance for the production of primers for the polymerase chain reaction (PCR), for oligonucleotide-based drugs, and for numerous other medical and biotechnological applications. The highly optimised automised chemical oligonucleotide synthesis relies upon phosphoramidites as the phosphate precursors and one of the drawbacks of this technology is the poor bench stability of phosphoramidites. Here, we report on the development of an on-demand flow synthesis of phosphoramidites from their corresponding alcohols, which is accomplished with short reaction times, near-quantitative yields and without the need of purification before being submitted directly to automated oligonucleotide synthesis. Sterically hindered as well as redox unstable phosphoramidites are synthesised using this methodology and the subsequent couplings are near-quantitative for all substrates. The vision for this technology is direct integration into DNA synthesisers thereby omitting manual synthesis and storage of phosphoramidites.

AB - Automated chemical synthesis of oligonucleotides is of fundamental importance for the production of primers for the polymerase chain reaction (PCR), for oligonucleotide-based drugs, and for numerous other medical and biotechnological applications. The highly optimised automised chemical oligonucleotide synthesis relies upon phosphoramidites as the phosphate precursors and one of the drawbacks of this technology is the poor bench stability of phosphoramidites. Here, we report on the development of an on-demand flow synthesis of phosphoramidites from their corresponding alcohols, which is accomplished with short reaction times, near-quantitative yields and without the need of purification before being submitted directly to automated oligonucleotide synthesis. Sterically hindered as well as redox unstable phosphoramidites are synthesised using this methodology and the subsequent couplings are near-quantitative for all substrates. The vision for this technology is direct integration into DNA synthesisers thereby omitting manual synthesis and storage of phosphoramidites.

UR - http://www.scopus.com/inward/record.url?scp=85105190442&partnerID=8YFLogxK

UR - https://www.nature.com/articles/s41467-021-22945-z

U2 - 10.1038/s41467-021-22945-z

DO - 10.1038/s41467-021-22945-z

M3 - Journal article

C2 - 33958587

AN - SCOPUS:85105190442

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 2760

ER -