Efficient synthesis of CN2097 using in situ activation of sulfhydryl group.
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| Title: | Efficient synthesis of CN2097 using in situ activation of sulfhydryl group. |
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| Authors: | Darwish, Shaban1,2, Parang, Keykavous1, Marshall, John3, Goebel, Dennis J.4, Tiwari, Rakesh1 tiwari@chapman.edu |
| Source: | Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry. Aug2017, Vol. 58 Issue 31, p3053-3056. 4p. |
| Subjects: | Sulfhydryl group, Peptidomimetics, Brain injuries, Angelman syndrome, Disulfides |
| Abstract: | CN2097 (R 7 Cs-sCYK[KTE(β-Ala)]V) is a rationally designed peptidomimetic that shows effectiveness in preclinical models for the treatment of neurological disorders, such as Angelman syndrome, traumatic brain injury (TBI), and stroke. Because of its potential therapeutic activity for the treatment of human CNS disorders, there was an urgent need to develop an efficient strategy for large-scale synthesis of CN2097. The synthesis of CN2097 was accomplished using Fmoc/tBu solid phase chemistry in multiple steps. Two different peptide fragments (activated polyarginine peptide Npys-sCR 7 and CYK[KTE(β-Ala)]V) were synthesized, followed by solution phase coupling in water. Activation of the polyarginine (CR 7 ) was achieved in situ during cleavage of protected peptide (C(Trt)R(Pbf) 7 ) from the Rink amide resin using 5 equiv. of 2,2-dithopyridine in TFA:TIS:H 2 O (95:2.5:2.5, v/v/v) for 4 h. The disulfide coupling was efficient which provided a 60% yield. [ABSTRACT FROM AUTHOR] |
| Copyright of Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 124113451 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Efficient synthesis of CN2097 using in situ activation of sulfhydryl group. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Darwish%2C+Shaban%22">Darwish, Shaban</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Parang%2C+Keykavous%22">Parang, Keykavous</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Marshall%2C+John%22">Marshall, John</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Goebel%2C+Dennis+J%2E%22">Goebel, Dennis J.</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Tiwari%2C+Rakesh%22">Tiwari, Rakesh</searchLink><relatesTo>1</relatesTo><i> tiwari@chapman.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Tetrahedron+Letters%3A+International+Organ+for+the+Rapid+Publication+of+Preliminary+Communications+in+Organic+Chemistry%22">Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry</searchLink>. Aug2017, Vol. 58 Issue 31, p3053-3056. 4p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Sulfhydryl+group%22">Sulfhydryl group</searchLink><br /><searchLink fieldCode="DE" term="%22Peptidomimetics%22">Peptidomimetics</searchLink><br /><searchLink fieldCode="DE" term="%22Brain+injuries%22">Brain injuries</searchLink><br /><searchLink fieldCode="DE" term="%22Angelman+syndrome%22">Angelman syndrome</searchLink><br /><searchLink fieldCode="DE" term="%22Disulfides%22">Disulfides</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: CN2097 (R 7 Cs-sCYK[KTE(β-Ala)]V) is a rationally designed peptidomimetic that shows effectiveness in preclinical models for the treatment of neurological disorders, such as Angelman syndrome, traumatic brain injury (TBI), and stroke. Because of its potential therapeutic activity for the treatment of human CNS disorders, there was an urgent need to develop an efficient strategy for large-scale synthesis of CN2097. The synthesis of CN2097 was accomplished using Fmoc/tBu solid phase chemistry in multiple steps. Two different peptide fragments (activated polyarginine peptide Npys-sCR 7 and CYK[KTE(β-Ala)]V) were synthesized, followed by solution phase coupling in water. Activation of the polyarginine (CR 7 ) was achieved in situ during cleavage of protected peptide (C(Trt)R(Pbf) 7 ) from the Rink amide resin using 5 equiv. of 2,2-dithopyridine in TFA:TIS:H 2 O (95:2.5:2.5, v/v/v) for 4 h. The disulfide coupling was efficient which provided a 60% yield. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.tetlet.2017.06.066 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 4 StartPage: 3053 Subjects: – SubjectFull: Sulfhydryl group Type: general – SubjectFull: Peptidomimetics Type: general – SubjectFull: Brain injuries Type: general – SubjectFull: Angelman syndrome Type: general – SubjectFull: Disulfides Type: general Titles: – TitleFull: Efficient synthesis of CN2097 using in situ activation of sulfhydryl group. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Darwish, Shaban – PersonEntity: Name: NameFull: Parang, Keykavous – PersonEntity: Name: NameFull: Marshall, John – PersonEntity: Name: NameFull: Goebel, Dennis J. – PersonEntity: Name: NameFull: Tiwari, Rakesh IsPartOfRelationships: – BibEntity: Dates: – D: 02 M: 08 Text: Aug2017 Type: published Y: 2017 Identifiers: – Type: issn-print Value: 00404039 Numbering: – Type: volume Value: 58 – Type: issue Value: 31 Titles: – TitleFull: Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry Type: main |
| ResultId | 1 |
