Intramolecular ester exchange of potent cytotoxic kulokekahilide-2

Masahiro Umehara, Yuuki Takada, Youichi Nakao, Junji Kimura

    Research output: Contribution to journalArticle

    9 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 languageEnglish
    Pages (from-to)840-843
    Number of pages4
    JournalTetrahedron Letters
    Volume50
    Issue number7
    DOIs
    Publication statusPublished - 2009 Feb 18

    Fingerprint

    Depsipeptides
    Cytotoxicity
    Esters
    HeLa Cells
    Amides
    Isomers
    Inhibitory Concentration 50
    Nuclear magnetic resonance
    kulokekahilide-2
    N-dodecyl-L-lysine amide
    3-(5-nitrofuryl)-7-(5-nitrofurfurylidene)-3,3a,4,5,6,7-hexahydro-2H-indazole

    Keywords

    • 24-membered cyclic depsipeptide
    • Cytotoxicity
    • Ester exchange
    • Kulokekahilide-2

    ASJC Scopus subject areas

    • Biochemistry
    • Organic Chemistry
    • Drug Discovery

    Cite this

    Intramolecular ester exchange of potent cytotoxic kulokekahilide-2. / Umehara, Masahiro; Takada, Yuuki; Nakao, Youichi; Kimura, Junji.

    In: Tetrahedron Letters, Vol. 50, No. 7, 18.02.2009, p. 840-843.

    Research output: Contribution to journalArticle

    Umehara, Masahiro ; Takada, Yuuki ; Nakao, Youichi ; Kimura, Junji. / Intramolecular ester exchange of potent cytotoxic kulokekahilide-2. In: Tetrahedron Letters. 2009 ; Vol. 50, No. 7. pp. 840-843.
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