Synthesis of the core enediyne structure of esperamicin-calichemicin class of antitumor antibiotics

✍ Scribed by Kiyoshi Tomioka; Hitoshi Fujita; Kenji Koga

• Book ID: 104233077
• Publisher: Elsevier Science
• Year: 1989
• Tongue: French
• Weight: 285 KB
• Volume: 30
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)80634-1

✦ Synopsis

The core structure of esperamicin-calichemicin series, bicyclo[7.3.l]enediyne 2, was synthesized in 9% overall yield in eight steps from cycbhexane-I ,2-dione and was shown to be stable at room temperature. The heart of esperamicin-calichemicin class of novel antitumor antibiotics (e.g., 1) is a bicyclol7.3.lltridecane system that combines a methyl trisulfide group, an endocyclic @-unsaturated ketone, and double and triple bonds in a 3-ene-1,5-diyne relationships.2-4 Enzymatic reduction of a trisulfide to a thiol triggers intramolecular Michael addition of the thiol to the enone, and subsequent Bergman enediyne cyclization to a phenylene diradical which can abstract protons from deoxyribose units in deoxyribonucleic acid resulting DNA strand breakage. Inspired by these fascinating structures, much efforts have been devoted toward design, synthesis, and evaluation of simple structures that might mimic the biological action of natural products.5