Tetrahydroxy 10-membered cyclic enediynes.
The preparation of cyclic 10-membered tetrahydroxy enediynes is reported. The synthesis starts from tartaric acid and allows the control of the relative stereochemistry. Acetal protection of the 2,3-hydroxy groups stabilizes the enediyne during synthesis. Removal of the cyclic protecting group with EtSH/TFA transforms the stable compounds into reactive enediynes, and the rate constants of their cyclization were determined in benzene and water. The cytoxicity of the activated compounds was assayed against tumor cells in vitro, but the growth inhibitory effect was weak compared to cisplatin.
Klein
Michael
M
Institut für Organische Chemie, Universität Regensburg, D-93040 Regensburg, Germany. burkhard.koenig@chemie.uni-regensburg.de
Zabel
Manfred
M
Bernhardt
Günther
G
König
Burkhard
B
D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003500:Cyclization; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008956:Models, Chemical; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013644:Tartrates / Q000737:chemistry*
D006841:Hydrocarbons, Aromatic; D013644:Tartrates; D002945:Cisplatin; C029768:tartaric acid