Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis
A scalable four-step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile, and acetone. Isolation and purificati...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
American Chemical Society (ACS)
2022
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| Online Access: | https://hdl.handle.net/1721.1/141084 |
| _version_ | 1826216146832982016 |
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| author | Gopalsamuthiram, Vijayagopal Kadam, Appasaheb L Noble, Jeffrey K Snead, David R Williams, Corshai Jamison, Timothy F Senanayake, Chris Yadaw, Ajay K Roy, Sarabindu Sirasani, Gopal Gupton, B Frank Burns, Justina Cook, Daniel W Stringham, Rodger W Ahmad, Saeed Krack, Rudy |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Gopalsamuthiram, Vijayagopal Kadam, Appasaheb L Noble, Jeffrey K Snead, David R Williams, Corshai Jamison, Timothy F Senanayake, Chris Yadaw, Ajay K Roy, Sarabindu Sirasani, Gopal Gupton, B Frank Burns, Justina Cook, Daniel W Stringham, Rodger W Ahmad, Saeed Krack, Rudy |
| author_sort | Gopalsamuthiram, Vijayagopal |
| collection | MIT |
| description | A scalable four-step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile, and acetone. Isolation and purification procedures are improved in comparison to our earlier study as all intermediates can be isolated via recrystallization. The key steps in the synthesis, namely, ester formation, hydroxyamination, and deprotection were carried out on a multigram scale to afford molnupiravir in 36-41% yield with an average purity of 98 wt % by qNMR and 99 area% by HPLC. |
| first_indexed | 2024-09-23T16:43:01Z |
| format | Article |
| id | mit-1721.1/141084 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:43:01Z |
| publishDate | 2022 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1410842023-01-25T20:35:08Z Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis Gopalsamuthiram, Vijayagopal Kadam, Appasaheb L Noble, Jeffrey K Snead, David R Williams, Corshai Jamison, Timothy F Senanayake, Chris Yadaw, Ajay K Roy, Sarabindu Sirasani, Gopal Gupton, B Frank Burns, Justina Cook, Daniel W Stringham, Rodger W Ahmad, Saeed Krack, Rudy Massachusetts Institute of Technology. Department of Chemistry A scalable four-step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile, and acetone. Isolation and purification procedures are improved in comparison to our earlier study as all intermediates can be isolated via recrystallization. The key steps in the synthesis, namely, ester formation, hydroxyamination, and deprotection were carried out on a multigram scale to afford molnupiravir in 36-41% yield with an average purity of 98 wt % by qNMR and 99 area% by HPLC. 2022-03-09T15:41:12Z 2022-03-09T15:41:12Z 2021-12-17 2022-03-09T15:35:58Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141084 Gopalsamuthiram, Vijayagopal, Kadam, Appasaheb L, Noble, Jeffrey K, Snead, David R, Williams, Corshai et al. 2021. "Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis." Organic Process Research & Development, 25 (12). en 10.1021/acs.oprd.1c00219 Organic Process Research & Development Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf American Chemical Society (ACS) ACS |
| spellingShingle | Gopalsamuthiram, Vijayagopal Kadam, Appasaheb L Noble, Jeffrey K Snead, David R Williams, Corshai Jamison, Timothy F Senanayake, Chris Yadaw, Ajay K Roy, Sarabindu Sirasani, Gopal Gupton, B Frank Burns, Justina Cook, Daniel W Stringham, Rodger W Ahmad, Saeed Krack, Rudy Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis |
| title | Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis |
| title_full | Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis |
| title_fullStr | Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis |
| title_full_unstemmed | Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis |
| title_short | Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis |
| title_sort | toward a practical nonenzymatic process for investigational covid 19 antiviral molnupiravir from cytidine supply centered synthesis |
| url | https://hdl.handle.net/1721.1/141084 |
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