TY - JOUR
T1 - Novel designed enediynes
T2 - Molecular design, chemical synthesis, mode of cycloaromatization and guanine-specific DNA cleavage
AU - Toshima, Kazunobu
AU - Ohta, Kazumi
AU - Kano, Takaaki
AU - Nakamura, Takatsugu
AU - Nakata, Masaya
AU - Kinoshita, Mitsuhiro
AU - Matsumura, Shuichi
N1 - Funding Information:
The authorss incerelyt hank Messrs TatsuyaO htake and Koji Yanagawafo r theire arlyc ontributiotno this project.F inancials upportb y a Grant-in-Aidf rom Amano Institute of Technology is gratefully acknowledged.
PY - 1996/1
Y1 - 1996/1
N2 - 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.
AB - 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.
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U2 - 10.1016/0968-0896(95)00170-0
DO - 10.1016/0968-0896(95)00170-0
M3 - Article
C2 - 8689230
AN - SCOPUS:0029964457
SN - 0968-0896
VL - 4
SP - 105
EP - 113
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 1
ER -