STRATEGY FOR THE SYNTHESIS OF EPOXIDE-CONTAINING AND CARBONATE-CONTAINING DIENEDIYNE MODELS OF THE NEOCARZINOSTATIN CHROMOPHORE - APPLICATION TO THE 6-RING 11-RING CASE/

A novel synthetic strategy leading to bicyclic dienediyne models of th e chromophore 1 of the anti-tumor antibiotic neocarzinostatin is descr ibed. Its key step is a ring-closing McMurry reaction of the dienediyn e keto aldehydes 17 or 23. It leads to dienediynediols (compounds 19 a nd 24, respectively) or to trienediynes (compounds 18 and 25, respecti vely). Low temperatures favor the formation of dienediynediols while h igh temperatures favor the formation of trienediynes, so that the McMu rry reactions of keto aldehyde 23 show an almost perfect temperature-d ependent chemoselectivity (Scheme 6). The trienediyne 25 contains a ke tal group which was removed by acid-catalyzed methanolysis (Scheme 8). The resulting diol 31 was mono-tert-butylsilylated to provide the all yl alcohol 36 (Scheme 10). It was epoxidized regio- and stereoselectiv ely with Sharpless' asymmetric epoxidation reagent. The resulting epox ide 37 was converted into the dienediyne epoxycarbonate syn-33 in the final step of a sequence totaling seven steps and 5% yield starting fr om the bistriflate 3b; 3b itself is accessible from 2-formylcyclohexan one in two steps and 47% overall yield. The dienediyne epoxycarbonate syn-33 is the first synthetic congener of the neocarzinostatin chromop hore furnished both with the - correctly configured - epoxide and carb onate rings.