Synthesis of a Coumarin-Based Analogue of Schweinfurthin F

Chloe M Schroeder; Patrick N Dey; John A Beutler; David F Wiemer

doi:10.1021/acs.joc.1c02046

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Synthesis of a Coumarin-Based Analogue of Schweinfurthin F

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Synthesis of a Coumarin-Based Analogue of Schweinfurthin F

Chloe M Schroeder, Patrick N Dey, John A Beutler and David F Wiemer

Journal of organic chemistry, Vol.86(23), pp.16824-16833

12/03/2021

DOI: 10.1021/acs.joc.1c02046

PMCID: PMC8650015

PMID: 34714084

Appears in UI Libraries Support Open Access

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Abstract

The natural schweinfurthins are stilbenes with significant antiproliferative activity and an uncertain mechanism of action. To obtain a fluorescent analogue with minimal deviation from the natural structure, a coumarin ring system was annulated to the D-ring, creating a new analogue of schweinfurthin F. This stilbene was prepared through a convergent synthesis, with a Horner–Wadsworth–Emmons condensation employed to form the central stilbene olefin. After preparation of a tricyclic phosphonate via a recent and more efficient modification of the classic Arbuzov reaction, condensation was attempted with an appropriately substituted bicyclic aldehyde but the coumarin system did not survive the reaction conditions. When olefin formation preceded generation of the coumarin, the stilbene formation proceeded smoothly and ultimately allowed access to the targeted coumarin-based schweinfurthin analogue. This analogue displayed the desired fluorescence properties along with significant biological activity in the National Cancer Institute’s 60-cell line bioassay, and the pattern of this biological activity mirrored that of the natural product schweinfurthin F. This approach gives facile access to new fluorescent analogues of the natural schweinfurthins and should be applicable to other natural stilbenes as well.

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Details

Title: Subtitle: Synthesis of a Coumarin-Based Analogue of Schweinfurthin F
Creators: Chloe M Schroeder - University of Iowa
Patrick N Dey - University of Iowa
John A Beutler - Molecular Targets Program, Center for Cancer Research
David F Wiemer - University of Iowa
Resource Type: Journal article
Publication Details: Journal of organic chemistry, Vol.86(23), pp.16824-16833
DOI: 10.1021/acs.joc.1c02046
PMID: 34714084
PMCID: PMC8650015
NLM abbreviation: J Org Chem
ISSN: 0022-3263
eISSN: 1520-6904
Publisher: American Chemical Society
Grant note: DOI: 10.13039/100000054, name: National Cancer Institute; DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust, award: 01-224
Language: English
Date published: 12/03/2021
Academic Unit: Neuroscience and Pharmacology; Chemistry
Record Identifier: 9984217460102771

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