Catalytic Enantioselective Synthesis of a Pyrrolizidine-Alkaloid-Inspired Compound Collection with Antiplasmodial Activity

Zhi Jun Jia; Hiroshi Takayama; Yushi Futamura; Harumi Aono; Jonathan O. Bauer; Carsten Strohmann; Andrey P. Antonchick; Hiroyuki Osada; Herbert Waldmann

doi:10.1021/acs.joc.7b03202

Catalytic Enantioselective Synthesis of a Pyrrolizidine-Alkaloid-Inspired Compound Collection with Antiplasmodial Activity

Zhi Jun Jia, Hiroshi Takayama, Yushi Futamura, Harumi Aono, Jonathan O. Bauer, Carsten Strohmann, Andrey P. Antonchick^*, Hiroyuki Osada, Herbert Waldmann

^*Corresponding author for this work

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

9 Citations (Scopus)

Abstract

A novel enantioselective approach to the synthesis of a compound collection inspired by natural pyrrolizidine alkaloids was developed, employing an enantioselectively catalyzed 1,3-dipolar cycloaddition as the key step. The cycloadducts were obtained with excellent enantio- and diastereoselectivity. Biological evaluation of the resulting compound collection revealed that the compound class has multiple bioactivities, including activity against Plasmodium falciparum 3D7 and inhibition of Hedgehog signaling.

Original language	English
Pages (from-to)	7033-7041
Number of pages	9
Journal	Journal of Organic Chemistry
Volume	83
Issue number	13
DOIs	https://doi.org/10.1021/acs.joc.7b03202
Publication status	Published - 2018 Jul 6
Externally published	Yes

ASJC Scopus subject areas

Organic Chemistry

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title = "Catalytic Enantioselective Synthesis of a Pyrrolizidine-Alkaloid-Inspired Compound Collection with Antiplasmodial Activity",

abstract = "A novel enantioselective approach to the synthesis of a compound collection inspired by natural pyrrolizidine alkaloids was developed, employing an enantioselectively catalyzed 1,3-dipolar cycloaddition as the key step. The cycloadducts were obtained with excellent enantio- and diastereoselectivity. Biological evaluation of the resulting compound collection revealed that the compound class has multiple bioactivities, including activity against Plasmodium falciparum 3D7 and inhibition of Hedgehog signaling.",

author = "Jia, {Zhi Jun} and Hiroshi Takayama and Yushi Futamura and Harumi Aono and Bauer, {Jonathan O.} and Carsten Strohmann and Antonchick, {Andrey P.} and Hiroyuki Osada and Herbert Waldmann",

note = "Funding Information: Z.-J.J. thanks the International Max-Planck-Research School in Chemical and Molecular Biology for a fellowship. This research was supported by the European Research Council under the Seventh Framework Programme of the European Union (FP7/2007-2013; ERC Grant 268309 to H.W.) and by the Max Planck Society. We thank Dr. Sonja Sievers and the compound management and screening center (COMAS) for compound screening. We thank Dr. Fuyu Ito, Ms. Naoko Morita, and Ms. Yasuko\ Hirata (RIKEN) for performing the antiproliferative activity tests. Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",

year = "2018",

month = jul,

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doi = "10.1021/acs.joc.7b03202",

language = "English",

volume = "83",

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journal = "Journal of Organic Chemistry",

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T1 - Catalytic Enantioselective Synthesis of a Pyrrolizidine-Alkaloid-Inspired Compound Collection with Antiplasmodial Activity

AU - Jia, Zhi Jun

AU - Takayama, Hiroshi

AU - Futamura, Yushi

AU - Aono, Harumi

AU - Bauer, Jonathan O.

AU - Strohmann, Carsten

AU - Antonchick, Andrey P.

AU - Osada, Hiroyuki

AU - Waldmann, Herbert

N1 - Funding Information: Z.-J.J. thanks the International Max-Planck-Research School in Chemical and Molecular Biology for a fellowship. This research was supported by the European Research Council under the Seventh Framework Programme of the European Union (FP7/2007-2013; ERC Grant 268309 to H.W.) and by the Max Planck Society. We thank Dr. Sonja Sievers and the compound management and screening center (COMAS) for compound screening. We thank Dr. Fuyu Ito, Ms. Naoko Morita, and Ms. Yasuko\ Hirata (RIKEN) for performing the antiproliferative activity tests. Publisher Copyright: © 2018 American Chemical Society.

PY - 2018/7/6

Y1 - 2018/7/6

N2 - A novel enantioselective approach to the synthesis of a compound collection inspired by natural pyrrolizidine alkaloids was developed, employing an enantioselectively catalyzed 1,3-dipolar cycloaddition as the key step. The cycloadducts were obtained with excellent enantio- and diastereoselectivity. Biological evaluation of the resulting compound collection revealed that the compound class has multiple bioactivities, including activity against Plasmodium falciparum 3D7 and inhibition of Hedgehog signaling.

AB - A novel enantioselective approach to the synthesis of a compound collection inspired by natural pyrrolizidine alkaloids was developed, employing an enantioselectively catalyzed 1,3-dipolar cycloaddition as the key step. The cycloadducts were obtained with excellent enantio- and diastereoselectivity. Biological evaluation of the resulting compound collection revealed that the compound class has multiple bioactivities, including activity against Plasmodium falciparum 3D7 and inhibition of Hedgehog signaling.

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Catalytic Enantioselective Synthesis of a Pyrrolizidine-Alkaloid-Inspired Compound Collection with Antiplasmodial Activity

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