Synthesis of an Epoxide‐ and Carbonate‐Containing 6‐/10‐Membered Bicyclodienediyne Analogue of the Neocarzinostaitin Chromophore

Abstract

AbstractThe monocyclo‐diendiyne → bicyclo‐trienediyne strategy for obtaining dienediyne models of the antitumor antibiotic neocarzinostatin chromophore (1) was extended from generating 6‐/11‐membered bicyclotrienediynes (e.g. 2 → 4) to generating the 6‐/10‐membered bicyclotrienediyne 5. In the preparatory steps (Scheme 2), the bistriflate 10 was successively coupled with alkynes 9 and 11. Via the dienediynediol and its subsequent oxidation with the Dess‐Martin periodinane, we obtained the monocyclic dienediyne keto aldehyde 13. Cyclization of 13 with low‐valent titanium afforded the bicyclotrienediyne 5 in 42% yield (Scheme 3). Compound 5 was converted in five steps – namely ketal cleavage, monosilylation of the resulting diol 14, asymmetric Sharpless epoxidation, desilylation and carbonate formation – into the dienediyne epoxycarbonate 3. The structure of the latter is more closely related to the neocarzinostatin chromophore than our earlier analogues.