Molecular design, chemical synthesis, and study of novel enediyne-sulfide systems related to the neocarzinostatin chromophore

Kazunobu Toshima, K. Ohta, A. Ohashi, T. Nakamura, M. Nakata, K. Tatsuta, S. Matsumura

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The design and synthesis of the novel monocyclic enediyne-sulfide systems and their chemical and DNA cleavage properties are described. The parent enediyne-sulfide 6 possessing a hydroxy group at the allylic position was effectively synthesized via the cross-coupling of the cis-vinyl iodide 11 and the acetylene derivative 12 using a Pd(0)-Cu(I) catalyst and the cyclization reaction of the acyclic dibromide 20 employing sodium sulfide as the key steps. In addition, the esterifications of 6 using appropriate procedures provided a series of its simple derivatives 21-29 and the hybrids 38-44 containing naturally occurring intercalators, all of which are quite stable when handled at ambient temperature. The representative enediyne-sulfide 22 was smoothly aromatized by 1,8-diazabicyclo[5.4.0]undec-7-ene in cyclohexa-1,4-diene through radical pathways and by a hydroxy anion in dimethyl sulfoxide-Tris-HCl, pH 8.5 buffer through a polar pathway. Furthermore, it was clearly found that all enediyne-sulfides cleaved DNA under alkaline conditions without any additive and the hybrids 38 and 44, each of which has the aromatic moiety of the neocarzinostatin chromophore and manzamins, respectively, exhibited the strongest DNA cleaving abilities with the identical high purine base (G > A) selectivity.

Original languageEnglish
Pages (from-to)4822-4831
Number of pages10
JournalJournal of the American Chemical Society
Volume117
Issue number17
Publication statusPublished - 1995

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Enediynes
Sulfides
Chromophores
DNA
Intercalating Agents
Derivatives
Acetylene
DNA Cleavage
Esterification
Cyclization
Dimethyl Sulfoxide
Dimethyl sulfoxide
Anions
Buffers
Negative ions
Catalysts
Temperature
Sodium
neocarzinostatin chromophore

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Molecular design, chemical synthesis, and study of novel enediyne-sulfide systems related to the neocarzinostatin chromophore. / Toshima, Kazunobu; Ohta, K.; Ohashi, A.; Nakamura, T.; Nakata, M.; Tatsuta, K.; Matsumura, S.

In: Journal of the American Chemical Society, Vol. 117, No. 17, 1995, p. 4822-4831.

Research output: Contribution to journalArticle

Toshima, Kazunobu ; Ohta, K. ; Ohashi, A. ; Nakamura, T. ; Nakata, M. ; Tatsuta, K. ; Matsumura, S. / Molecular design, chemical synthesis, and study of novel enediyne-sulfide systems related to the neocarzinostatin chromophore. In: Journal of the American Chemical Society. 1995 ; Vol. 117, No. 17. pp. 4822-4831.
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