Diels-Alder Reaction-Aromatization Approach toward Functionalized Ring C Allocolchicinoids. Enantioselective Total Synthesis of (-)-7S-Allocolchicine.
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| Title: | Diels-Alder Reaction-Aromatization Approach toward Functionalized Ring C Allocolchicinoids. Enantioselective Total Synthesis of (-)-7S-Allocolchicine. |
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| Authors: | Vorogushin, Andrei V., Predeus, Alexander V., Wulff, William D., Hansen, Hans-Jürgen |
| Source: | Journal of Organic Chemistry. 7/25/2003, Vol. 68 Issue 15, p5826. 6p. 10 Diagrams, 1 Chart. |
| Subjects: | Colchicine, Antimitotic agents, Biosynthesis |
| Abstract: | Allocolchicinoids are analogues of the important antimitotic compound (-)-colchicine 1. A strategy is reported for the synthesis of ring C functionalized allocolchicinoids, which is based on a DielsAlder reaction-aromatization sequence. This route is complementary to the previously disclosed benzannulation approach involving Fischer carbene complexes and alkynes. Dienes 12 and 14 incorporate the natural substitution pattern on ring A and undergo Diels-Alder reactions with various dienophiles. Subsequent aromatization affords the set of differently functionalized ring C allocolchicinoids 15-19, 23, and 25, with high regioselectively and in moderate to good yields. An intramolecular Diels-Alder reaction-aromatization sequence allows for access to allocolchicinoids with reversed regiochemical introduction of ring C substituents. The equilibria of the atropisomers of 15 and 19 are studied in three NMR solvents. Reactions of the dienes 12 and 14 with DMAD lead to the corresponding cycloadducts, but the subsequent aromatization is complicated. A regioselective Diels-Alder reaction-aromatization sequence is utilized as the key step in the first stereoselective total synthesis of (-)-allocolchicine 2. Asymmetric introduction of hydroxy group at C7 is achieved by the enantioselective reduction of ketone 29. The correct stereochemistry is then established by Mitsunobu inversion reaction using Zn(N[sub 3])[sub 2]-2Py. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Organic Chemistry is the property of American Chemical Society 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: 10433127 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Diels-Alder Reaction-Aromatization Approach toward Functionalized Ring C Allocolchicinoids. Enantioselective Total Synthesis of (-)-7S-Allocolchicine. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Vorogushin%2C+Andrei+V%2E%22">Vorogushin, Andrei V.</searchLink><br /><searchLink fieldCode="AR" term="%22Predeus%2C+Alexander+V%2E%22">Predeus, Alexander V.</searchLink><br /><searchLink fieldCode="AR" term="%22Wulff%2C+William+D%2E%22">Wulff, William D.</searchLink><br /><searchLink fieldCode="AR" term="%22Hansen%2C+Hans-Jürgen%22">Hansen, Hans-Jürgen</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Organic+Chemistry%22">Journal of Organic Chemistry</searchLink>. 7/25/2003, Vol. 68 Issue 15, p5826. 6p. 10 Diagrams, 1 Chart. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Colchicine%22">Colchicine</searchLink><br /><searchLink fieldCode="DE" term="%22Antimitotic+agents%22">Antimitotic agents</searchLink><br /><searchLink fieldCode="DE" term="%22Biosynthesis%22">Biosynthesis</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Allocolchicinoids are analogues of the important antimitotic compound (-)-colchicine 1. A strategy is reported for the synthesis of ring C functionalized allocolchicinoids, which is based on a DielsAlder reaction-aromatization sequence. This route is complementary to the previously disclosed benzannulation approach involving Fischer carbene complexes and alkynes. Dienes 12 and 14 incorporate the natural substitution pattern on ring A and undergo Diels-Alder reactions with various dienophiles. Subsequent aromatization affords the set of differently functionalized ring C allocolchicinoids 15-19, 23, and 25, with high regioselectively and in moderate to good yields. An intramolecular Diels-Alder reaction-aromatization sequence allows for access to allocolchicinoids with reversed regiochemical introduction of ring C substituents. The equilibria of the atropisomers of 15 and 19 are studied in three NMR solvents. Reactions of the dienes 12 and 14 with DMAD lead to the corresponding cycloadducts, but the subsequent aromatization is complicated. A regioselective Diels-Alder reaction-aromatization sequence is utilized as the key step in the first stereoselective total synthesis of (-)-allocolchicine 2. Asymmetric introduction of hydroxy group at C7 is achieved by the enantioselective reduction of ketone 29. The correct stereochemistry is then established by Mitsunobu inversion reaction using Zn(N[sub 3])[sub 2]-2Py. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Organic Chemistry is the property of American Chemical Society 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: 10.1021/jo034420t Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 6 StartPage: 5826 Subjects: – SubjectFull: Colchicine Type: general – SubjectFull: Antimitotic agents Type: general – SubjectFull: Biosynthesis Type: general Titles: – TitleFull: Diels-Alder Reaction-Aromatization Approach toward Functionalized Ring C Allocolchicinoids. Enantioselective Total Synthesis of (-)-7S-Allocolchicine. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Vorogushin, Andrei V. – PersonEntity: Name: NameFull: Predeus, Alexander V. – PersonEntity: Name: NameFull: Wulff, William D. – PersonEntity: Name: NameFull: Hansen, Hans-Jürgen IsPartOfRelationships: – BibEntity: Dates: – D: 25 M: 07 Text: 7/25/2003 Type: published Y: 2003 Identifiers: – Type: issn-print Value: 00223263 Numbering: – Type: volume Value: 68 – Type: issue Value: 15 Titles: – TitleFull: Journal of Organic Chemistry Type: main |
| ResultId | 1 |
