Solid-phase synthesis of structurally diverse heterocycles by an amide-ketone condensation/N-acyliminium Pictet-Spengler sequence
An efficient approach for the solid-phase synthesis of structurally diverse heterocyclic compounds is presented. Under acidic reaction conditions, peptidic levulinamides undergo intramolecular ketone–amide condensation reactions to form cyclic N-acyliminium intermediates. In the presence of a tether...
| Main Authors: | , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2013
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| Online Access: | https://hdl.handle.net/10356/99417 http://hdl.handle.net/10220/13003 |
| _version_ | 1811693864125202432 |
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| author | Givskov, Michael Komnatnyy, Vitaly V. Nielsen, Thomas E. |
| author_facet | Givskov, Michael Komnatnyy, Vitaly V. Nielsen, Thomas E. |
| author_sort | Givskov, Michael |
| collection | NTU |
| description | An efficient approach for the solid-phase synthesis of structurally diverse heterocyclic compounds is presented. Under acidic reaction conditions, peptidic levulinamides undergo intramolecular ketone–amide condensation reactions to form cyclic N-acyliminium intermediates. In the presence of a tethered nucleophile, a second cyclization reaction results in the formation of a fused bicyclic ring system. The scope of the methodology was demonstrated by several combinations of substituted ketones and nucleophiles, the latter conveniently originating from amino acids with functionalized side chains, such as tryptophan, substituted phenylalanines, and cysteine. The cyclization sequence provides diastereomerically pure products in high yields. In one extension of the methodology, the resulting relative stereochemistry of the products enables the formation of bridged ring systems by a unique cyclative release mechanism. |
| first_indexed | 2024-10-01T06:58:27Z |
| format | Journal Article |
| id | ntu-10356/99417 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:58:27Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/994172020-03-07T12:47:10Z Solid-phase synthesis of structurally diverse heterocycles by an amide-ketone condensation/N-acyliminium Pictet-Spengler sequence Givskov, Michael Komnatnyy, Vitaly V. Nielsen, Thomas E. An efficient approach for the solid-phase synthesis of structurally diverse heterocyclic compounds is presented. Under acidic reaction conditions, peptidic levulinamides undergo intramolecular ketone–amide condensation reactions to form cyclic N-acyliminium intermediates. In the presence of a tethered nucleophile, a second cyclization reaction results in the formation of a fused bicyclic ring system. The scope of the methodology was demonstrated by several combinations of substituted ketones and nucleophiles, the latter conveniently originating from amino acids with functionalized side chains, such as tryptophan, substituted phenylalanines, and cysteine. The cyclization sequence provides diastereomerically pure products in high yields. In one extension of the methodology, the resulting relative stereochemistry of the products enables the formation of bridged ring systems by a unique cyclative release mechanism. 2013-08-05T06:00:40Z 2019-12-06T20:06:58Z 2013-08-05T06:00:40Z 2019-12-06T20:06:58Z 2012 2012 Journal Article Komnatnyy, V. V., Givskov, M.,& Nielsen, T. E. (2012). Solid-Phase Synthesis of Structurally Diverse Heterocycles by an Amide-Ketone Condensation/N-Acyliminium Pictet-Spengler Sequence. Chemistry - A European Journal, 18(52), 16793-16800. 0947-6539 https://hdl.handle.net/10356/99417 http://hdl.handle.net/10220/13003 10.1002/chem.201202745 en Chemistry - a European journal |
| spellingShingle | Givskov, Michael Komnatnyy, Vitaly V. Nielsen, Thomas E. Solid-phase synthesis of structurally diverse heterocycles by an amide-ketone condensation/N-acyliminium Pictet-Spengler sequence |
| title | Solid-phase synthesis of structurally diverse heterocycles by an amide-ketone condensation/N-acyliminium Pictet-Spengler sequence |
| title_full | Solid-phase synthesis of structurally diverse heterocycles by an amide-ketone condensation/N-acyliminium Pictet-Spengler sequence |
| title_fullStr | Solid-phase synthesis of structurally diverse heterocycles by an amide-ketone condensation/N-acyliminium Pictet-Spengler sequence |
| title_full_unstemmed | Solid-phase synthesis of structurally diverse heterocycles by an amide-ketone condensation/N-acyliminium Pictet-Spengler sequence |
| title_short | Solid-phase synthesis of structurally diverse heterocycles by an amide-ketone condensation/N-acyliminium Pictet-Spengler sequence |
| title_sort | solid phase synthesis of structurally diverse heterocycles by an amide ketone condensation n acyliminium pictet spengler sequence |
| url | https://hdl.handle.net/10356/99417 http://hdl.handle.net/10220/13003 |
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