Catalytic Asymmetric Synthesis of the anti‐COVID‐19 Drug Remdesivir
The catalytic asymmetric synthesis of the anti‐COVID‐19 drug Remdesivir has been realized by the coupling of the P‐racemic phosphoryl chloride with protected nucleoside GS441524. The chiral bicyclic imidazole catalyst used is crucial for the dynamic kinetic asymmetric transformation (DyKAT) to proce...
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| Veröffentlicht in: | Angewandte Chemie 2020-11, Vol.132 (47), p.21000-21005 |
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| creator | Wang, Mo Zhang, Lu Huo, Xiaohong Zhang, Zhenfeng Yuan, Qianjia Li, Panpan Chen, Jianzhong Zou, Yashi Wu, Zhengxing Zhang, Wanbin |
| description | The catalytic asymmetric synthesis of the anti‐COVID‐19 drug Remdesivir has been realized by the coupling of the P‐racemic phosphoryl chloride with protected nucleoside GS441524. The chiral bicyclic imidazole catalyst used is crucial for the dynamic kinetic asymmetric transformation (DyKAT) to proceed smoothly with high reactivity and excellent stereoselectivity (96 % conv., 22:1 SP:RP). Mechanistic studies showed that this DyKAT is a first‐order visual kinetic reaction dependent on the catalyst concentration. The unique chiral bicyclic imidazole skeleton and carbamate substituent of the catalyst are both required for the racemization process, involving the phosphoryl chloride, and subsequent stereodiscriminating step. A 10 gram scale reaction was also conducted with comparably excellent results, showing its potential for industrial application.
The first catalytic asymmetric synthesis of Remdesivir by the coupling of the P‐racemic phosphoryl chloride with protected nucleoside GS441524 has been realized using a chiral bicyclic imidazole catalyst, which is crucial for the racemization process involving the phosphoryl chloride and subsequent stereodiscriminating step (96 % conv., 22:1 SP:RP). Furthermore, a 10 gram scale reaction was successfully realized, showing its potential for industrial application. |
| doi_str_mv | 10.1002/ange.202011527 |
| format | Article |
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The first catalytic asymmetric synthesis of Remdesivir by the coupling of the P‐racemic phosphoryl chloride with protected nucleoside GS441524 has been realized using a chiral bicyclic imidazole catalyst, which is crucial for the racemization process involving the phosphoryl chloride and subsequent stereodiscriminating step (96 % conv., 22:1 SP:RP). Furthermore, a 10 gram scale reaction was successfully realized, showing its potential for industrial application.</description><identifier>ISSN: 0044-8249</identifier><identifier>EISSN: 1521-3757</identifier><identifier>DOI: 10.1002/ange.202011527</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>asymmetric catalysis ; Asymmetric synthesis ; Asymmetry ; Catalysts ; Chemical synthesis ; Chemistry ; Chlorides ; COVID-19 ; drug design ; Imidazole ; Industrial applications ; organocatalysis ; phosphoramidates ; Racemization ; Stereoselectivity ; synthetic methods</subject><ispartof>Angewandte Chemie, 2020-11, Vol.132 (47), p.21000-21005</ispartof><rights>2020 Wiley‐VCH GmbH</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2027-e2a82355502a26278fb2fd1a0079c47b152b1202ce37d65148542945f82833383</citedby><cites>FETCH-LOGICAL-c2027-e2a82355502a26278fb2fd1a0079c47b152b1202ce37d65148542945f82833383</cites><orcidid>0000-0002-4788-4195</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fange.202011527$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fange.202011527$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Wang, Mo</creatorcontrib><creatorcontrib>Zhang, Lu</creatorcontrib><creatorcontrib>Huo, Xiaohong</creatorcontrib><creatorcontrib>Zhang, Zhenfeng</creatorcontrib><creatorcontrib>Yuan, Qianjia</creatorcontrib><creatorcontrib>Li, Panpan</creatorcontrib><creatorcontrib>Chen, Jianzhong</creatorcontrib><creatorcontrib>Zou, Yashi</creatorcontrib><creatorcontrib>Wu, Zhengxing</creatorcontrib><creatorcontrib>Zhang, Wanbin</creatorcontrib><title>Catalytic Asymmetric Synthesis of the anti‐COVID‐19 Drug Remdesivir</title><title>Angewandte Chemie</title><description>The catalytic asymmetric synthesis of the anti‐COVID‐19 drug Remdesivir has been realized by the coupling of the P‐racemic phosphoryl chloride with protected nucleoside GS441524. The chiral bicyclic imidazole catalyst used is crucial for the dynamic kinetic asymmetric transformation (DyKAT) to proceed smoothly with high reactivity and excellent stereoselectivity (96 % conv., 22:1 SP:RP). Mechanistic studies showed that this DyKAT is a first‐order visual kinetic reaction dependent on the catalyst concentration. The unique chiral bicyclic imidazole skeleton and carbamate substituent of the catalyst are both required for the racemization process, involving the phosphoryl chloride, and subsequent stereodiscriminating step. A 10 gram scale reaction was also conducted with comparably excellent results, showing its potential for industrial application.
The first catalytic asymmetric synthesis of Remdesivir by the coupling of the P‐racemic phosphoryl chloride with protected nucleoside GS441524 has been realized using a chiral bicyclic imidazole catalyst, which is crucial for the racemization process involving the phosphoryl chloride and subsequent stereodiscriminating step (96 % conv., 22:1 SP:RP). Furthermore, a 10 gram scale reaction was successfully realized, showing its potential for industrial application.</description><subject>asymmetric catalysis</subject><subject>Asymmetric synthesis</subject><subject>Asymmetry</subject><subject>Catalysts</subject><subject>Chemical synthesis</subject><subject>Chemistry</subject><subject>Chlorides</subject><subject>COVID-19</subject><subject>drug design</subject><subject>Imidazole</subject><subject>Industrial applications</subject><subject>organocatalysis</subject><subject>phosphoramidates</subject><subject>Racemization</subject><subject>Stereoselectivity</subject><subject>synthetic methods</subject><issn>0044-8249</issn><issn>1521-3757</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkM1OwzAQhC0EEqVw5RyJc8p6bdfOsUpLqFRRib-r5aZOSdUkxU5BufEIPCNPgqsiOHKaOXyzOxpCLikMKABem3plBwgIlAqUR6QXhMZMCnlMegCcxwp5ckrOvF8DwBBl0iNZalqz6doyj0a-qyrbumAfurp9sb70UVNEwUWmbsuvj890_jwdB6VJNHa7VXRvq2XA3kp3Tk4Ks_H24kf75Olm8pjexrN5Nk1HszgPzWRs0ShkQghAg6GBKhZYLKkBkEnO5SJUXtBA5pbJ5VBQrgTHhItCoWKMKdYnV4e7W9e87qxv9brZuTq81MiFkjhUUgRqcKBy13jvbKG3rqyM6zQFvR9L78fSv2OFQHIIvJcb2_1D69FdNvnLfgOOLWyW</recordid><startdate>20201116</startdate><enddate>20201116</enddate><creator>Wang, Mo</creator><creator>Zhang, Lu</creator><creator>Huo, Xiaohong</creator><creator>Zhang, Zhenfeng</creator><creator>Yuan, Qianjia</creator><creator>Li, Panpan</creator><creator>Chen, Jianzhong</creator><creator>Zou, Yashi</creator><creator>Wu, Zhengxing</creator><creator>Zhang, Wanbin</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0002-4788-4195</orcidid></search><sort><creationdate>20201116</creationdate><title>Catalytic Asymmetric Synthesis of the anti‐COVID‐19 Drug Remdesivir</title><author>Wang, Mo ; Zhang, Lu ; Huo, Xiaohong ; Zhang, Zhenfeng ; Yuan, Qianjia ; Li, Panpan ; Chen, Jianzhong ; Zou, Yashi ; Wu, Zhengxing ; Zhang, Wanbin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2027-e2a82355502a26278fb2fd1a0079c47b152b1202ce37d65148542945f82833383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>asymmetric catalysis</topic><topic>Asymmetric synthesis</topic><topic>Asymmetry</topic><topic>Catalysts</topic><topic>Chemical synthesis</topic><topic>Chemistry</topic><topic>Chlorides</topic><topic>COVID-19</topic><topic>drug design</topic><topic>Imidazole</topic><topic>Industrial applications</topic><topic>organocatalysis</topic><topic>phosphoramidates</topic><topic>Racemization</topic><topic>Stereoselectivity</topic><topic>synthetic methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Mo</creatorcontrib><creatorcontrib>Zhang, Lu</creatorcontrib><creatorcontrib>Huo, Xiaohong</creatorcontrib><creatorcontrib>Zhang, Zhenfeng</creatorcontrib><creatorcontrib>Yuan, Qianjia</creatorcontrib><creatorcontrib>Li, Panpan</creatorcontrib><creatorcontrib>Chen, Jianzhong</creatorcontrib><creatorcontrib>Zou, Yashi</creatorcontrib><creatorcontrib>Wu, Zhengxing</creatorcontrib><creatorcontrib>Zhang, Wanbin</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Angewandte Chemie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Mo</au><au>Zhang, Lu</au><au>Huo, Xiaohong</au><au>Zhang, Zhenfeng</au><au>Yuan, Qianjia</au><au>Li, Panpan</au><au>Chen, Jianzhong</au><au>Zou, Yashi</au><au>Wu, Zhengxing</au><au>Zhang, Wanbin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Catalytic Asymmetric Synthesis of the anti‐COVID‐19 Drug Remdesivir</atitle><jtitle>Angewandte Chemie</jtitle><date>2020-11-16</date><risdate>2020</risdate><volume>132</volume><issue>47</issue><spage>21000</spage><epage>21005</epage><pages>21000-21005</pages><issn>0044-8249</issn><eissn>1521-3757</eissn><abstract>The catalytic asymmetric synthesis of the anti‐COVID‐19 drug Remdesivir has been realized by the coupling of the P‐racemic phosphoryl chloride with protected nucleoside GS441524. The chiral bicyclic imidazole catalyst used is crucial for the dynamic kinetic asymmetric transformation (DyKAT) to proceed smoothly with high reactivity and excellent stereoselectivity (96 % conv., 22:1 SP:RP). Mechanistic studies showed that this DyKAT is a first‐order visual kinetic reaction dependent on the catalyst concentration. The unique chiral bicyclic imidazole skeleton and carbamate substituent of the catalyst are both required for the racemization process, involving the phosphoryl chloride, and subsequent stereodiscriminating step. A 10 gram scale reaction was also conducted with comparably excellent results, showing its potential for industrial application.
The first catalytic asymmetric synthesis of Remdesivir by the coupling of the P‐racemic phosphoryl chloride with protected nucleoside GS441524 has been realized using a chiral bicyclic imidazole catalyst, which is crucial for the racemization process involving the phosphoryl chloride and subsequent stereodiscriminating step (96 % conv., 22:1 SP:RP). Furthermore, a 10 gram scale reaction was successfully realized, showing its potential for industrial application.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/ange.202011527</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-4788-4195</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | asymmetric catalysis Asymmetric synthesis Asymmetry Catalysts Chemical synthesis Chemistry Chlorides COVID-19 drug design Imidazole Industrial applications organocatalysis phosphoramidates Racemization Stereoselectivity synthetic methods |
| title | Catalytic Asymmetric Synthesis of the anti‐COVID‐19 Drug Remdesivir |
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