A Divergent Enantioselective Strategy for the Synthesis of Griseusins

Yinan Zhang; Qing Ye; Xiachang Wang; Qing Bai She; Jon S. Thorson

doi:10.1002/anie.201505022

A Divergent Enantioselective Strategy for the Synthesis of Griseusins

Yinan Zhang, Qing Ye, Xiachang Wang, Qing Bai She, Jon S. Thorson

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

The first enantioselective total synthesis of griseusin A, griseusin C, 4′-deacetyl-griseusin A, and two non-native counterparts in 11–14 steps is reported. This strategy highlights a key hydroxy-directed CH olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. Colorectal cancer cell cytotoxicities of the final products highlight the impact of the griseusin tetrahydro-spiropyran ring on bioactivity. As the first divergent enantioselective synthesis, the strategy put forth sets the stage for further griseusin mechanism-of-action and SAR studies.

Original language	English
Pages (from-to)	11219-11222
Number of pages	4
Journal	Angewandte Chemie - International Edition
Volume	54
Issue number	38
DOIs	https://doi.org/10.1002/anie.201505022
State	Published - Sep 14 2015

Bibliographical note

Funding Information:
This work was supported, in part, by the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, National Institutes of Health grant CA175105 (Q.‐B. She), and the National Center for Advancing Translational Sciences (UL1TR000117).

Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

CH activation
aromatic polyketides
natural products
pyranonaphthoquinones
total synthesis

ASJC Scopus subject areas

Catalysis
Chemistry (all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/anie.201505022

Cite this

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title = "A Divergent Enantioselective Strategy for the Synthesis of Griseusins",

abstract = "The first enantioselective total synthesis of griseusin A, griseusin C, 4′-deacetyl-griseusin A, and two non-native counterparts in 11–14 steps is reported. This strategy highlights a key hydroxy-directed CH olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. Colorectal cancer cell cytotoxicities of the final products highlight the impact of the griseusin tetrahydro-spiropyran ring on bioactivity. As the first divergent enantioselective synthesis, the strategy put forth sets the stage for further griseusin mechanism-of-action and SAR studies.",

keywords = "CH activation, aromatic polyketides, natural products, pyranonaphthoquinones, total synthesis",

author = "Yinan Zhang and Qing Ye and Xiachang Wang and She, {Qing Bai} and Thorson, {Jon S.}",

note = "Funding Information: This work was supported, in part, by the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, National Institutes of Health grant CA175105 (Q.‐B. She), and the National Center for Advancing Translational Sciences (UL1TR000117). Publisher Copyright: {\textcopyright} 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

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doi = "10.1002/anie.201505022",

language = "English",

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AU - Ye, Qing

AU - Wang, Xiachang

AU - She, Qing Bai

AU - Thorson, Jon S.

N1 - Funding Information: This work was supported, in part, by the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, National Institutes of Health grant CA175105 (Q.‐B. She), and the National Center for Advancing Translational Sciences (UL1TR000117). Publisher Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2015/9/14

Y1 - 2015/9/14

N2 - The first enantioselective total synthesis of griseusin A, griseusin C, 4′-deacetyl-griseusin A, and two non-native counterparts in 11–14 steps is reported. This strategy highlights a key hydroxy-directed CH olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. Colorectal cancer cell cytotoxicities of the final products highlight the impact of the griseusin tetrahydro-spiropyran ring on bioactivity. As the first divergent enantioselective synthesis, the strategy put forth sets the stage for further griseusin mechanism-of-action and SAR studies.

AB - The first enantioselective total synthesis of griseusin A, griseusin C, 4′-deacetyl-griseusin A, and two non-native counterparts in 11–14 steps is reported. This strategy highlights a key hydroxy-directed CH olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. Colorectal cancer cell cytotoxicities of the final products highlight the impact of the griseusin tetrahydro-spiropyran ring on bioactivity. As the first divergent enantioselective synthesis, the strategy put forth sets the stage for further griseusin mechanism-of-action and SAR studies.

KW - CH activation

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KW - natural products

KW - pyranonaphthoquinones

KW - total synthesis

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A Divergent Enantioselective Strategy for the Synthesis of Griseusins

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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