Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug
The construction of duocarmycin-like compounds is often associated with lengthy synthetic routes. Presented herein is the development of a short and convenient synthesis of a type of duocarmycin prodrug. The 1,2,3,6-tetrahydropyrrolo[3,2-<i>e</i>]indole-containing core is here constructe...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/12/4818 |
| _version_ | 1827736148466728960 |
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| author | Christoffer Bengtsson Ylva Gravenfors |
| author_facet | Christoffer Bengtsson Ylva Gravenfors |
| author_sort | Christoffer Bengtsson |
| collection | DOAJ |
| description | The construction of duocarmycin-like compounds is often associated with lengthy synthetic routes. Presented herein is the development of a short and convenient synthesis of a type of duocarmycin prodrug. The 1,2,3,6-tetrahydropyrrolo[3,2-<i>e</i>]indole-containing core is here constructed from commercially available Boc-5-bromoindole in four steps and 23% overall yield, utilizing a Buchwald–Hartwig amination followed by a sodium hydride-induced regioselective bromination. In addition, protocols for selective mono- and di-halogenations of positions 3 and 4 were also developed, which could be useful for further exploration of this scaffold. |
| first_indexed | 2024-03-11T02:05:56Z |
| format | Article |
| id | doaj.art-0d5e4ca584234c7a8cad35fabbee579a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T02:05:56Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0d5e4ca584234c7a8cad35fabbee579a2023-11-18T11:50:45ZengMDPI AGMolecules1420-30492023-06-012812481810.3390/molecules28124818Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like ProdrugChristoffer Bengtsson0Ylva Gravenfors1Drug Discovery & Development Platform, Science for Life Laboratory, Department of Organic Chemistry, Stockholm University, Tomtebodavägen 23a, 17165 Solna, SwedenDrug Discovery & Development Platform, Science for Life Laboratory, Department of Organic Chemistry, Stockholm University, Tomtebodavägen 23a, 17165 Solna, SwedenThe construction of duocarmycin-like compounds is often associated with lengthy synthetic routes. Presented herein is the development of a short and convenient synthesis of a type of duocarmycin prodrug. The 1,2,3,6-tetrahydropyrrolo[3,2-<i>e</i>]indole-containing core is here constructed from commercially available Boc-5-bromoindole in four steps and 23% overall yield, utilizing a Buchwald–Hartwig amination followed by a sodium hydride-induced regioselective bromination. In addition, protocols for selective mono- and di-halogenations of positions 3 and 4 were also developed, which could be useful for further exploration of this scaffold.https://www.mdpi.com/1420-3049/28/12/4818duocarmycinprodrugselective halogenation1,2,3,6-tetrahydropyrrolo[3,2-<i>e</i>]indole |
| spellingShingle | Christoffer Bengtsson Ylva Gravenfors Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug Molecules duocarmycin prodrug selective halogenation 1,2,3,6-tetrahydropyrrolo[3,2-<i>e</i>]indole |
| title | Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug |
| title_full | Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug |
| title_fullStr | Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug |
| title_full_unstemmed | Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug |
| title_short | Rapid Construction of a Chloromethyl-Substituted Duocarmycin-like Prodrug |
| title_sort | rapid construction of a chloromethyl substituted duocarmycin like prodrug |
| topic | duocarmycin prodrug selective halogenation 1,2,3,6-tetrahydropyrrolo[3,2-<i>e</i>]indole |
| url | https://www.mdpi.com/1420-3049/28/12/4818 |
| work_keys_str_mv | AT christofferbengtsson rapidconstructionofachloromethylsubstitutedduocarmycinlikeprodrug AT ylvagravenfors rapidconstructionofachloromethylsubstitutedduocarmycinlikeprodrug |