| 研究課題/領域番号 |
20K15966
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| 研究機関 | 公益財団法人微生物化学研究会 |
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研究代表者 |
崔 進 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (20839120)
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| 研究期間 (年度) |
2020-04-01 – 2023-03-31
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| キーワード | vinylogous addition / chromone / enolates / total synthesis / natural product |
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| 研究実績の概要 |
In this study, a novel and stereodivergent approach to chromanone lactones has been developed through copper-catalyzed asymmetric vinylogous addition of siloxyfurans to 2-ester-substituted chromones. The current catalytic system features the use of chiral ligands to control the diastereo- and enantioselective addition of copper vinylogous enolate to 2-ester-substituted chromones, with suppression of undesired retro-addition pathways by silyl additives. Mechanism studies indicated that the use of (EtO)2Si(OAc)2 as additive is crucial to achieve high stereoselectivities by trapping the reversible intermediate. The reaction proceeds smoothly with a variety of unactivated 2-ester-substituted chromones bearing diverse substituents and provides natural product analogs with outstanding diastereo- and enantioselectivities. The dr and ee for anti-type adduct is up to >99% ee and >19:1 dr; the dr and ee for syn-type adduct is up to 96% ee and >25:1 dr. The developed method was applied for the total synthesis of ent-blennolide B with precise stereochemical control. Based on the reported method, the formal synthesis of secalonic acid A could also be realized using ent-blennolide B as the intermediate.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
The project is progressing better than expected. By screening different reaction conditions, a novel and robust catalytic system which could deliver desired adducts using 2-ester-substituted chromones as substrates for total synthesis of natural products has been found. The developed approach allowed for the efficient synthesis of (-)-blennolide B with precise stereochemical control, which provides a formal synthesis of secalonic acid A.
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| 今後の研究の推進方策 |
A comprehensive study of current results will be performed, including the understanding of reaction mechanism and origin of stereoselectivities, and further application for the synthesis of natural products.
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| 備考 |
微生物化学研究所HP
https://www.bikaken.or.jp/
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