2021 Fiscal Year Research-status Report
The Development of Direct Vinylogous Michael Addition of Butenolides to Chromones and Its Application to the Total Synthesis of Natural Products
| Project/Area Number |
20K15966
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| Research Institution | Microbial Chemistry Research Foundation |
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Principal Investigator |
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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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | vinylogous addition / chromone / enolates / total synthesis / natural product |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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| Remarks |
微生物化学研究所HP
https://www.bikaken.or.jp/
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