Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (-)-Preussin B, and 3-Deoxy-(+)-preussin B.
Efficient de novo asymmetric syntheses of (+)-preussin B, the C(2)-epimer of (-)-preussin B, and 3-deoxy-(+)-preussin B have been developed, using the diastereoselective conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl 4-phenylbut-2-enoate and diastereoselective reduc...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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American Chemical Society
2016
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| _version_ | 1797067744170999808 |
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| author | Buchman, M Csatayová, K Davies, S Fletcher, A Houlsby, I Roberts, P Rowe, S Thomson, J |
| author_facet | Buchman, M Csatayová, K Davies, S Fletcher, A Houlsby, I Roberts, P Rowe, S Thomson, J |
| author_sort | Buchman, M |
| collection | OXFORD |
| description | Efficient de novo asymmetric syntheses of (+)-preussin B, the C(2)-epimer of (-)-preussin B, and 3-deoxy-(+)-preussin B have been developed, using the diastereoselective conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl 4-phenylbut-2-enoate and diastereoselective reductive cyclizations of γ-amino ketones as the key steps to set the stereochemistry. Conjugate addition followed by enolate protonation generated the corresponding β-amino ester. Homologation using the ester functionality as a synthetic handle gave the corresponding γ-amino ketone. Hydrogenolytic N-debenzylation was accompanied by diastereoselective reductive cyclization in situ; reductive N-methylation then gave 3-deoxy-(+)-preussin B as the major diastereoisomeric product. Meanwhile, the same conjugate addition but followed by enolate oxidation with (+)-camphorsulfonyloxaziridine gave the corresponding anti-α-hydroxy-β-amino ester. α-Epimerization by oxidation and diastereoselective reduction then gave access to the corresponding syn-α-hydroxy-β-amino ester. Homologation of both of these diastereoisomeric α-hydroxy-β-amino esters gave the corresponding β-hydroxy-γ-amino ketones. N-Debenzylation and concomitant diastereoselective reductive cyclization, followed by reductive N-methylation, provided the C(2)-epimer of (-)-preussin B and (+)-preussin B as the major diastereoisomeric products, respectively. The overall yields (from phenylacetaldehyde) were 19% for 3-deoxy-(+)-preussin B over seven steps, 8% for the C(2)-epimer of (-)-preussin B over nine steps, and 7% for (+)-preussin B over eleven steps. |
| first_indexed | 2024-03-06T22:00:42Z |
| format | Journal article |
| id | oxford-uuid:4e7c4fb6-ebe7-4bea-b8ee-fe94772250fd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:00:42Z |
| publishDate | 2016 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:4e7c4fb6-ebe7-4bea-b8ee-fe94772250fd2022-03-26T16:01:24ZAsymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (-)-Preussin B, and 3-Deoxy-(+)-preussin B.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4e7c4fb6-ebe7-4bea-b8ee-fe94772250fdEnglishSymplectic Elements at OxfordAmerican Chemical Society2016Buchman, MCsatayová, KDavies, SFletcher, AHoulsby, IRoberts, PRowe, SThomson, JEfficient de novo asymmetric syntheses of (+)-preussin B, the C(2)-epimer of (-)-preussin B, and 3-deoxy-(+)-preussin B have been developed, using the diastereoselective conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl 4-phenylbut-2-enoate and diastereoselective reductive cyclizations of γ-amino ketones as the key steps to set the stereochemistry. Conjugate addition followed by enolate protonation generated the corresponding β-amino ester. Homologation using the ester functionality as a synthetic handle gave the corresponding γ-amino ketone. Hydrogenolytic N-debenzylation was accompanied by diastereoselective reductive cyclization in situ; reductive N-methylation then gave 3-deoxy-(+)-preussin B as the major diastereoisomeric product. Meanwhile, the same conjugate addition but followed by enolate oxidation with (+)-camphorsulfonyloxaziridine gave the corresponding anti-α-hydroxy-β-amino ester. α-Epimerization by oxidation and diastereoselective reduction then gave access to the corresponding syn-α-hydroxy-β-amino ester. Homologation of both of these diastereoisomeric α-hydroxy-β-amino esters gave the corresponding β-hydroxy-γ-amino ketones. N-Debenzylation and concomitant diastereoselective reductive cyclization, followed by reductive N-methylation, provided the C(2)-epimer of (-)-preussin B and (+)-preussin B as the major diastereoisomeric products, respectively. The overall yields (from phenylacetaldehyde) were 19% for 3-deoxy-(+)-preussin B over seven steps, 8% for the C(2)-epimer of (-)-preussin B over nine steps, and 7% for (+)-preussin B over eleven steps. |
| spellingShingle | Buchman, M Csatayová, K Davies, S Fletcher, A Houlsby, I Roberts, P Rowe, S Thomson, J Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (-)-Preussin B, and 3-Deoxy-(+)-preussin B. |
| title | Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (-)-Preussin B, and 3-Deoxy-(+)-preussin B. |
| title_full | Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (-)-Preussin B, and 3-Deoxy-(+)-preussin B. |
| title_fullStr | Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (-)-Preussin B, and 3-Deoxy-(+)-preussin B. |
| title_full_unstemmed | Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (-)-Preussin B, and 3-Deoxy-(+)-preussin B. |
| title_short | Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (-)-Preussin B, and 3-Deoxy-(+)-preussin B. |
| title_sort | asymmetric syntheses of preussin b the c 2 epimer of preussin b and 3 deoxy preussin b |
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