Hydroxylation of eleuthoside synthetic intermediates by P450BM3 (CYP102A1)
A seven‐step synthesis of the first tricyclic intermediate in Danishefsky's total synthesis of eleutherobin is reported with Wittig homologation and sequential additions of metallated furan derivatives to aldehydes as key steps. Aiming to prepare hydroxylated eleutherobin analogues for cytotoxi...
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| Format: | Journal article |
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Wiley
2018
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| _version_ | 1797079922572787712 |
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| author | Syntrivanis, L Wong, L Robertson, J |
| author_facet | Syntrivanis, L Wong, L Robertson, J |
| author_sort | Syntrivanis, L |
| collection | OXFORD |
| description | A seven‐step synthesis of the first tricyclic intermediate in Danishefsky's total synthesis of eleutherobin is reported with Wittig homologation and sequential additions of metallated furan derivatives to aldehydes as key steps. Aiming to prepare hydroxylated eleutherobin analogues for cytotoxicity screening, the furan diol epimers 6 and precursors 1 and 2 were exposed to a 48‐member panel of engineered cytochrome P450BM3 variants. Both furan‐containing substrates reacted solely at the furan ring, one resulting in overall biocatalytic Achmatowicz reaction. Selective hydroxylation at four separate sp3 C–H centres was achieved in the substrates lacking the furan component. P450BM3‐catalysed hydroxylation of racemic substrates can proceed with kinetic resolution; in the case reported here, the 2°‐allylic alcohol product 10 was generated with an 82:18 enantiomeric ratio. |
| first_indexed | 2024-03-07T00:52:47Z |
| format | Journal article |
| id | oxford-uuid:86f6209b-7e5c-4267-a81b-9488c2bb00f9 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:52:47Z |
| publishDate | 2018 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:86f6209b-7e5c-4267-a81b-9488c2bb00f92022-03-26T22:07:39ZHydroxylation of eleuthoside synthetic intermediates by P450BM3 (CYP102A1)Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:86f6209b-7e5c-4267-a81b-9488c2bb00f9Symplectic Elements at OxfordWiley2018Syntrivanis, LWong, LRobertson, JA seven‐step synthesis of the first tricyclic intermediate in Danishefsky's total synthesis of eleutherobin is reported with Wittig homologation and sequential additions of metallated furan derivatives to aldehydes as key steps. Aiming to prepare hydroxylated eleutherobin analogues for cytotoxicity screening, the furan diol epimers 6 and precursors 1 and 2 were exposed to a 48‐member panel of engineered cytochrome P450BM3 variants. Both furan‐containing substrates reacted solely at the furan ring, one resulting in overall biocatalytic Achmatowicz reaction. Selective hydroxylation at four separate sp3 C–H centres was achieved in the substrates lacking the furan component. P450BM3‐catalysed hydroxylation of racemic substrates can proceed with kinetic resolution; in the case reported here, the 2°‐allylic alcohol product 10 was generated with an 82:18 enantiomeric ratio. |
| spellingShingle | Syntrivanis, L Wong, L Robertson, J Hydroxylation of eleuthoside synthetic intermediates by P450BM3 (CYP102A1) |
| title | Hydroxylation of eleuthoside synthetic intermediates by P450BM3 (CYP102A1) |
| title_full | Hydroxylation of eleuthoside synthetic intermediates by P450BM3 (CYP102A1) |
| title_fullStr | Hydroxylation of eleuthoside synthetic intermediates by P450BM3 (CYP102A1) |
| title_full_unstemmed | Hydroxylation of eleuthoside synthetic intermediates by P450BM3 (CYP102A1) |
| title_short | Hydroxylation of eleuthoside synthetic intermediates by P450BM3 (CYP102A1) |
| title_sort | hydroxylation of eleuthoside synthetic intermediates by p450bm3 cyp102a1 |
| work_keys_str_mv | AT syntrivanisl hydroxylationofeleuthosidesyntheticintermediatesbyp450bm3cyp102a1 AT wongl hydroxylationofeleuthosidesyntheticintermediatesbyp450bm3cyp102a1 AT robertsonj hydroxylationofeleuthosidesyntheticintermediatesbyp450bm3cyp102a1 |