[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 |
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| Authors: | Rebecca L. Grange Dr. Michael J. Gallen Dr. Heiko Schill Dr. Jenny P. Johns Lin Dong Dr. Peter G. Parsons Dr. Paul W. Reddell Dr. Victoria A. Gordon Dr. Paul V. Bernhardt Dr. Craig M. Williams Dr. |
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| Affiliation: | 1. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, 4072, Queensland (Australia), Fax: (+61)?7‐3365‐4299;2. Queensland Institute of Medical Research, P O Royal Brisbane Hospital, Brisbane, 4029, Queensland (Australia);3. EcoBiotics Limited, PO Box 1, Yungaburra, 4884, Queensland (Australia) |
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| Abstract: | 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. |
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| Keywords: | antitumor agents bicyclo compounds cycloaddition cyclooctatetraene diazo compounds Diels– Alder reaction |
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