A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component Condensation
Pasireotide is a multi-receptor ligand somatostatin analogue approved for medical treatment of Cushing’s disease and acromegaly. The liquid-phase total synthesis of pasireotide-a 18-membered cyclic hexapeptide-was achieved by the 3 + 2 + 1 strategy, and the Pro<sup>1</sup>-Phe&...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/11/2185 |
| _version_ | 1830416151720493056 |
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| author | Chunying Ma Miao Chen Weiming Chu Jiayi Tao Delong Kong Mengmeng Zhang Wenhua Feng |
| author_facet | Chunying Ma Miao Chen Weiming Chu Jiayi Tao Delong Kong Mengmeng Zhang Wenhua Feng |
| author_sort | Chunying Ma |
| collection | DOAJ |
| description | Pasireotide is a multi-receptor ligand somatostatin analogue approved for medical treatment of Cushing’s disease and acromegaly. The liquid-phase total synthesis of pasireotide-a 18-membered cyclic hexapeptide-was achieved by the 3 + 2 + 1 strategy, and the Pro<sup>1</sup>-Phe<sup>6</sup> peptide bond was selected as the final cyclization position. Two key fragments were simply synthesized using <i>N</i>,<i>O</i>-bis(trimethylsilyl)acetamide/<i>N</i>-hydroxysuccinimide ester (BSA/NHS) as coupling agents, and processes of the two key fragments were simple without any chromatographic purification. The current synthesis method is easily scalable and produces the target peptide with an overall yield of 15%. |
| first_indexed | 2024-12-20T21:19:35Z |
| format | Article |
| id | doaj.art-ac06bf5eb1584fc1814708a19a455e81 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-20T21:19:35Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ac06bf5eb1584fc1814708a19a455e812022-12-21T19:26:19ZengMDPI AGMolecules1420-30492019-06-012411218510.3390/molecules24112185molecules24112185A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component CondensationChunying Ma0Miao Chen1Weiming Chu2Jiayi Tao3Delong Kong4Mengmeng Zhang5Wenhua Feng6Department of New Drug Research and Development, Institute of Materia Medical, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaDepartment of New Drug Research and Development, Institute of Materia Medical, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaDepartment of New Drug Research and Development, Institute of Materia Medical, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaDepartment of New Drug Research and Development, Institute of Materia Medical, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaDepartment of New Drug Research and Development, Institute of Materia Medical, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaDepartment of New Drug Research and Development, Institute of Materia Medical, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaDepartment of New Drug Research and Development, Institute of Materia Medical, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaPasireotide is a multi-receptor ligand somatostatin analogue approved for medical treatment of Cushing’s disease and acromegaly. The liquid-phase total synthesis of pasireotide-a 18-membered cyclic hexapeptide-was achieved by the 3 + 2 + 1 strategy, and the Pro<sup>1</sup>-Phe<sup>6</sup> peptide bond was selected as the final cyclization position. Two key fragments were simply synthesized using <i>N</i>,<i>O</i>-bis(trimethylsilyl)acetamide/<i>N</i>-hydroxysuccinimide ester (BSA/NHS) as coupling agents, and processes of the two key fragments were simple without any chromatographic purification. The current synthesis method is easily scalable and produces the target peptide with an overall yield of 15%.https://www.mdpi.com/1420-3049/24/11/2185pasireotideliquid-phasesynthesisBSA/NHScyclic hexapeptide |
| spellingShingle | Chunying Ma Miao Chen Weiming Chu Jiayi Tao Delong Kong Mengmeng Zhang Wenhua Feng A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component Condensation Molecules pasireotide liquid-phase synthesis BSA/NHS cyclic hexapeptide |
| title | A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component Condensation |
| title_full | A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component Condensation |
| title_fullStr | A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component Condensation |
| title_full_unstemmed | A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component Condensation |
| title_short | A Practical and Total Synthesis of Pasireotide: Synthesis of Cyclic Hexapeptide via a Three-Component Condensation |
| title_sort | practical and total synthesis of pasireotide synthesis of cyclic hexapeptide via a three component condensation |
| topic | pasireotide liquid-phase synthesis BSA/NHS cyclic hexapeptide |
| url | https://www.mdpi.com/1420-3049/24/11/2185 |
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