Intramolecular ester exchange of potent cytotoxic kulokekahilide-2

Masahiro Umehara; Yuuki Takada; Yoichi Nakao; Junji Kimura

doi:10.1016/j.tetlet.2008.12.018

Intramolecular ester exchange of potent cytotoxic kulokekahilide-2

Masahiro Umehara, Yuuki Takada, Yoichi Nakao, Junji Kimura^*

^*Corresponding author for this work

School of Advanced Science and Engineering

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

10 Citations (Scopus)

Abstract

Kulokekahilide-2 is a 26-membered cyclic depsipeptide that exhibits potent cytotoxicity against HeLa and P388 cells with IC₅₀ values of 3.2 and 16 ng/mL, respectively. We have achieved a total synthesis of natural kulokekahilide-2, the NMR spectra of which showed complex signals because of trans and cis conformers at the amide bond. Besides, the spectra revealed that a mixture of 26- and 24-membered cyclic depsipeptides had been produced due to intramolecular ester exchange. The isolated 24-membered compound was transformed into the 26-membered compound over a period of several days. The two isomers have been shown to be in equilibrium and to display almost the same cytotoxicity.

Original language	English
Pages (from-to)	840-843
Number of pages	4
Journal	Tetrahedron Letters
Volume	50
Issue number	7
DOIs	https://doi.org/10.1016/j.tetlet.2008.12.018
Publication status	Published - 2009 Feb 18

Keywords

24-membered cyclic depsipeptide
Cytotoxicity
Ester exchange
Kulokekahilide-2

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tetlet.2008.12.018

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title = "Intramolecular ester exchange of potent cytotoxic kulokekahilide-2",

abstract = "Kulokekahilide-2 is a 26-membered cyclic depsipeptide that exhibits potent cytotoxicity against HeLa and P388 cells with IC50 values of 3.2 and 16 ng/mL, respectively. We have achieved a total synthesis of natural kulokekahilide-2, the NMR spectra of which showed complex signals because of trans and cis conformers at the amide bond. Besides, the spectra revealed that a mixture of 26- and 24-membered cyclic depsipeptides had been produced due to intramolecular ester exchange. The isolated 24-membered compound was transformed into the 26-membered compound over a period of several days. The two isomers have been shown to be in equilibrium and to display almost the same cytotoxicity.",

keywords = "24-membered cyclic depsipeptide, Cytotoxicity, Ester exchange, Kulokekahilide-2",

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T1 - Intramolecular ester exchange of potent cytotoxic kulokekahilide-2

AU - Umehara, Masahiro

AU - Takada, Yuuki

AU - Nakao, Yoichi

AU - Kimura, Junji

PY - 2009/2/18

Y1 - 2009/2/18

N2 - Kulokekahilide-2 is a 26-membered cyclic depsipeptide that exhibits potent cytotoxicity against HeLa and P388 cells with IC50 values of 3.2 and 16 ng/mL, respectively. We have achieved a total synthesis of natural kulokekahilide-2, the NMR spectra of which showed complex signals because of trans and cis conformers at the amide bond. Besides, the spectra revealed that a mixture of 26- and 24-membered cyclic depsipeptides had been produced due to intramolecular ester exchange. The isolated 24-membered compound was transformed into the 26-membered compound over a period of several days. The two isomers have been shown to be in equilibrium and to display almost the same cytotoxicity.

AB - Kulokekahilide-2 is a 26-membered cyclic depsipeptide that exhibits potent cytotoxicity against HeLa and P388 cells with IC50 values of 3.2 and 16 ng/mL, respectively. We have achieved a total synthesis of natural kulokekahilide-2, the NMR spectra of which showed complex signals because of trans and cis conformers at the amide bond. Besides, the spectra revealed that a mixture of 26- and 24-membered cyclic depsipeptides had been produced due to intramolecular ester exchange. The isolated 24-membered compound was transformed into the 26-membered compound over a period of several days. The two isomers have been shown to be in equilibrium and to display almost the same cytotoxicity.

KW - 24-membered cyclic depsipeptide

KW - Cytotoxicity

KW - Ester exchange

KW - Kulokekahilide-2

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JO - Tetrahedron Letters

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Intramolecular ester exchange of potent cytotoxic kulokekahilide-2

Abstract

Keywords

ASJC Scopus subject areas

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