Catalytic prenyl conjugate additions for synthesis of enantiomerically enriched PPAPs

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of >400 natural products with a broad spectrum of bioactivity, ranging from antidepressant and antimicrobial to anti-obesity and anticancer activity. Here, we present a scalable, regio-, site-, and enantioselective catalytic method for synthesis of cyclic β-prenyl ketones, compounds that can be used for efficient syntheses of many PPAPs in high enantiomeric purity. The transformation is prenyl conjugate addition to cyclic β-ketoesters promoted by a readily accessible chiral copper catalyst and involving an easy-to-prepare and isolable organoborate reagent. Reactions reach completion in just a few minutes at room temperature. The importance of this advance is highlighted by the enantioselective preparation of intermediates previously used to generate racemic PPAPs. We also present the enantioselective synthesis of nemorosonol (14 steps, 20% yield) and its one-step conversion to another PPAP, garcibracteatone (52% yield).

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Publication Details

Journal
Science
Published
2024-10-10
DOI
https://doi.org/10.1126/science.adr8612
Citations
13
Primary Topic
Synthesis of Indole Derivatives
Type
article
Field-Weighted Citation Impact
3.25

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article

Catalytic prenyl conjugate additions for synthesis of enantiomerically enriched PPAPs

Can Qin, Shawn Voon Hwee Ng, Peng Liu, Yuebiao Zhou et al.
13 citations
Science
Synthesis of Indole Derivatives
3.25
article

Catalytic prenyl conjugate additions for synthesis of enantiomerically enriched PPAPs

Can Qin, Shawn Voon Hwee Ng, Peng Liu, Yuebiao Zhou, Casey Howshall, Amir H. Hoveyda, Binh Khanh Mai, Filippo Romiti, Kai Ze Tee, T. Ho
article en
13 citations

Abstract

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of >400 natural products with a broad spectrum of bioactivity, ranging from antidepressant and antimicrobial to anti-obesity and anticancer activity. Here, we present a scalable, regio-, site-, and enantioselective catalytic method for synthesis of cyclic β-prenyl ketones, compounds that can be used for efficient syntheses of many PPAPs in high enantiomeric purity. The transformation is prenyl conjugate addition to cyclic β-ketoesters promoted by a readily accessible chiral copper catalyst and involving an easy-to-prepare and isolable organoborate reagent. Reactions reach completion in just a few minutes at room temperature. The importance of this advance is highlighted by the enantioselective preparation of intermediates previously used to generate racemic PPAPs. We also present the enantioselective synthesis of nemorosonol (14 steps, 20% yield) and its one-step conversion to another PPAP, garcibracteatone (52% yield).

ScienceVol. 386(6718)
Boston College (US), The University of Texas at Dallas (US), University of Pittsburgh (US), Institut de Science et d'Ingénierie Supramoléculaires (FR)
National Science Foundation, Cancer Prevention and Research Institute of Texas, Boston College, University of Texas Southwestern Medical Center, University of Pittsburgh, European Commission, National Institutes of Health, National Cancer Institute, Office of Advanced Cyberinfrastructure, Division of Chemistry
Openalex Percentile: Top 7%
Synthesis of Indole Derivatives
3.25
DOIOpen Access PDFOpenAlex
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