Total synthesis of isoprekinamycin: structural evidence for enhanced diazonium ion character and growth inhibitory activity toward cancer cells.
The structurally novel diazobenzo[a]fluorene antibiotic isoprekinamycin (IPK) has been synthesized for the first time employing a Suzuki coupling of a brominated AB ring synthon with a boronate ester representing the D ring, followed by anionic cyclization and appropriate functional group manipulations. The first indication that the diazobenzo[a]fluorene system exhibits in vitro anticancer activity is provided and X-ray crystallographic evidence for enhancement of diazonium ion character as a consequence of intramolecular H-bonding is described.
Liu
Wei
W
Department of Chemistry, University of Waterloo, Waterloo, Ontario, Canada.
Buck
Matthew
M
Chen
Nan
N
Shang
Muhong
M
Taylor
Nicholas J
NJ
Asoud
Jalil
J
Wu
Xing
X
Hasinoff
Brian B
BB
Dmitrienko
Gary I
GI
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D003500:Cyclization; D003979:Diazonium Compounds / Q000737:chemistry*; D005449:Fluorenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D015394:Molecular Structure
D000970:Antineoplastic Agents; D003979:Diazonium Compounds; D005449:Fluorenes; C523171:isoprekinamycin