Novel designed enediynes: molecular design, chemical synthesis, mode of cycloaromatization and guanine-specific DNA cleavage.
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.
Toshima
K
K
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Ohta
K
K
Kano
T
T
Nakamura
T
T
Nakata
M
M
Kinoshita
M
M
Matsumura
S
S
D000480:Alkynes; D000900:Anti-Bacterial Agents / Q000737:chemistry; D000903:Antibiotics, Antineoplastic; D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D053281:Enediynes; D006147:Guanine / Q000737:chemistry*; D010455:Peptides; D013329:Structure-Activity Relationship; D009353:Zinostatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*
C100561:1-(benzoyloxy)-2-cyclodecene-4,9-diyne-6,7,8-triol; D000480:Alkynes; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D001565:Benzoates; D053281:Enediynes; D010455:Peptides; D006147:Guanine; C032372:neocarzinostatin chromophore; D004247:DNA; D009353:Zinostatin