Synthesis and biological activities of the 3,5-disubstituted indolizidine poison frog alkaloid 239Q and its congeners

Xu Wang; Hiroshi Tsuneki; Noriko Urata; Yasuhiro Tezuka; Tsutomu Wada; Toshiyasu Sasaoka; Hideki Sakai; Ralph A. Saporito; Naoki Toyooka

doi:10.1002/ejoc.201200974

Synthesis and biological activities of the 3,5-disubstituted indolizidine poison frog alkaloid 239Q and its congeners

Xu Wang, Hiroshi Tsuneki^*, Noriko Urata, Yasuhiro Tezuka, Tsutomu Wada, Toshiyasu Sasaoka, Hideki Sakai, Ralph A. Saporito, Naoki Toyooka

^*Corresponding author for this work

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

15 Scopus citations

Abstract

The first total synthesis of the 3,5-disubstituted indolizidine toad alkaloid 239Q from the known pyrrolidine 1 has been achieved, in seven steps with a 35 % overall yield. The relative stereochemistry of natural 239Q was determined unambiguously by comparison of GC-FTIR spectra of synthetic material with the skin extracts of the toad Melanophryniscus cupreuscapularis. The C7 congeners at the 5-position (12 and 13) showed strong antagonist activities on the α4β2 nicotinic acetylcholine receptors.

Original language	English
Pages (from-to)	7082-7092
Number of pages	11
Journal	European Journal of Organic Chemistry
Issue number	36
DOIs	https://doi.org/10.1002/ejoc.201200974
State	Published - 2012/12

Keywords

Alkaloids
Medicinal chemistry
Melanophryniscus cupreuscapularis
Melanophryniscus klappenbachi
Natural products
Total synthesis

ASJC Scopus subject areas

Physical and Theoretical Chemistry
Organic Chemistry

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10.1002/ejoc.201200974

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title = "Synthesis and biological activities of the 3,5-disubstituted indolizidine poison frog alkaloid 239Q and its congeners",

abstract = "The first total synthesis of the 3,5-disubstituted indolizidine toad alkaloid 239Q from the known pyrrolidine 1 has been achieved, in seven steps with a 35 % overall yield. The relative stereochemistry of natural 239Q was determined unambiguously by comparison of GC-FTIR spectra of synthetic material with the skin extracts of the toad Melanophryniscus cupreuscapularis. The C7 congeners at the 5-position (12 and 13) showed strong antagonist activities on the α4β2 nicotinic acetylcholine receptors.",

keywords = "Alkaloids, Medicinal chemistry, Melanophryniscus cupreuscapularis, Melanophryniscus klappenbachi, Natural products, Total synthesis",

author = "Xu Wang and Hiroshi Tsuneki and Noriko Urata and Yasuhiro Tezuka and Tsutomu Wada and Toshiyasu Sasaoka and Hideki Sakai and Saporito, {Ralph A.} and Naoki Toyooka",

year = "2012",

month = dec,

doi = "10.1002/ejoc.201200974",

language = "英語",

pages = "7082--7092",

journal = "European Journal of Organic Chemistry",

issn = "1434-193X",

publisher = "Wiley-VCH Verlag",

number = "36",

}

TY - JOUR

T1 - Synthesis and biological activities of the 3,5-disubstituted indolizidine poison frog alkaloid 239Q and its congeners

AU - Wang, Xu

AU - Tsuneki, Hiroshi

AU - Urata, Noriko

AU - Tezuka, Yasuhiro

AU - Wada, Tsutomu

AU - Sasaoka, Toshiyasu

AU - Sakai, Hideki

AU - Saporito, Ralph A.

AU - Toyooka, Naoki

PY - 2012/12

Y1 - 2012/12

N2 - The first total synthesis of the 3,5-disubstituted indolizidine toad alkaloid 239Q from the known pyrrolidine 1 has been achieved, in seven steps with a 35 % overall yield. The relative stereochemistry of natural 239Q was determined unambiguously by comparison of GC-FTIR spectra of synthetic material with the skin extracts of the toad Melanophryniscus cupreuscapularis. The C7 congeners at the 5-position (12 and 13) showed strong antagonist activities on the α4β2 nicotinic acetylcholine receptors.

AB - The first total synthesis of the 3,5-disubstituted indolizidine toad alkaloid 239Q from the known pyrrolidine 1 has been achieved, in seven steps with a 35 % overall yield. The relative stereochemistry of natural 239Q was determined unambiguously by comparison of GC-FTIR spectra of synthetic material with the skin extracts of the toad Melanophryniscus cupreuscapularis. The C7 congeners at the 5-position (12 and 13) showed strong antagonist activities on the α4β2 nicotinic acetylcholine receptors.

KW - Alkaloids

KW - Medicinal chemistry

KW - Melanophryniscus cupreuscapularis

KW - Melanophryniscus klappenbachi

KW - Natural products

KW - Total synthesis

UR - http://www.scopus.com/inward/record.url?scp=84870593253&partnerID=8YFLogxK

U2 - 10.1002/ejoc.201200974

DO - 10.1002/ejoc.201200974

M3 - 学術論文

AN - SCOPUS:84870593253

SN - 1434-193X

SP - 7082

EP - 7092

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

IS - 36

ER -

Synthesis and biological activities of the 3,5-disubstituted indolizidine poison frog alkaloid 239Q and its congeners

Abstract

Keywords

ASJC Scopus subject areas

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