[4+2] cycloaddition reactions between 1,8-disubstituted cyclooctatetraenes and diazo dienophiles: stereoelectronic effects, anticancer properties and application to the synthesis of 7,8-substituted bicyclo[4.2.0]octa-2,4-dienes.
A detailed examination of [4+2] cycloaddition reactions between 1,8-disubstituted cyclooctatetraenes and diazo compounds revealed that 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) reacts to form either 2,3- or 3,4-disubstituted adducts. The product distribution can be controlled by modulating the electron density of the cyclooctatetraene. Unprecedented [4+2] cycloadditions between diisopropyl azodicarboxylate (DIAD) and 1,8-disubstituted cyclooctatetraenes are also described and further manipulation of a resulting cycloadduct uncovered a new pathway to the synthetically challenging bicyclo[4.2.0]octa-2,4-diene family. Variation of the substituents resulted in a range of compounds displaying selective action against different human tumour cell types.
Grange
Rebecca L
RL
School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, 4072, Queensland, Australia.
Gallen
Michael J
MJ
Schill
Heiko
H
Johns
Jenny P
JP
Dong
Lin
L
Parsons
Peter G
PG
Reddell
Paul W
PW
Gordon
Victoria A
VA
Bernhardt
Paul V
PV
Williams
Craig M
CM
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001391:Azo Compounds / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D004224:Diterpenes / Q000138:chemical synthesis*; D006801:Humans; D008872:Microwaves; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry
D000970:Antineoplastic Agents; D001391:Azo Compounds; D001643:Bridged Bicyclo Compounds; D004224:Diterpenes; D014230:Triazoles; C053540:4-phenyl-1,2,4-triazoline-3,5-dione