Novel designed enediynes: Molecular design, chemical synthesis, mode of cycloaromatization and guanine-specific DNA cleavage

Kazunobu Toshima, Kazumi Ohta, Takaaki Kano, Takatsugu Nakamura, Masaya Nakata, Mitsuhiro Kinoshita, Shuichi Matsumura

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The molecular design and chemical synthesis of novel enediyne molecules related to the neocarzinostatin chromophore (1), and their chemical and DNA cleaving properties are described. The 10-membered enediyne triols 16-18 were effectively synthesized from xylitol (10) in a short step, and found to be quite stable when handled at room temperature. The representative and acylated enediyne 16 was cycloaromatized by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in cyclohexa-1,4-diene-benzene to give the benzenoid product 21 through a radical pathway. On the other hand, the enediyne 16 was cycloaromatized by diethylamine in dimethyl sulfoxide-Tris-HCl, pH 8.5 buffer to afford another benzenoid product 22 as a diethylamine adduct through a polar pathway. Furthermore, the enediynes 16-18 were found to exhibit guanine-specific DNA cleavage under weakly basic conditions with no additive.

Original languageEnglish
Pages (from-to)105-113
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume4
Issue number1
DOIs
Publication statusPublished - 1996

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Enediynes
DNA Cleavage
Guanine
DNA
Xylitol
Dimethyl Sulfoxide
Benzene
Buffers
Molecules
Temperature

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Novel designed enediynes : Molecular design, chemical synthesis, mode of cycloaromatization and guanine-specific DNA cleavage. / Toshima, Kazunobu; Ohta, Kazumi; Kano, Takaaki; Nakamura, Takatsugu; Nakata, Masaya; Kinoshita, Mitsuhiro; Matsumura, Shuichi.

In: Bioorganic and Medicinal Chemistry, Vol. 4, No. 1, 1996, p. 105-113.

Research output: Contribution to journalArticle

Toshima, Kazunobu ; Ohta, Kazumi ; Kano, Takaaki ; Nakamura, Takatsugu ; Nakata, Masaya ; Kinoshita, Mitsuhiro ; Matsumura, Shuichi. / Novel designed enediynes : Molecular design, chemical synthesis, mode of cycloaromatization and guanine-specific DNA cleavage. In: Bioorganic and Medicinal Chemistry. 1996 ; Vol. 4, No. 1. pp. 105-113.
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