UC San Diego

The cytotoxicity and anti-tumor potential of the naturally occurring enediynes has generated a flurry of activity in the scientific community since their discovery in the 1980s. Much research has been conducted towards gaining increased control over the triggering of this cycloaromatization reaction, usually with the aim of making it better suited for medicinal applications. Less emphasis has been placed on the merits of the so-called "Bergman cycloaromatization" as a synthetic tool, due in part to the high temperatures required to trigger cyclization, as well as the frequently low product yields as a result of competing polymerization. Our research has explored both of these aspects of enediyne chemistry. First, we describe the preparation of ferrocenyl enediynes I and II, which are extremely photosensitive; when exposed to sunlight in the presence of "Triphos," each undergoes ring-slippage of the iron from the functionalized Cp ring to form III and IV, respectively. Crystal structures and absorption profiles of I-IV are provided and discussed. The challenging synthesis of ferrocenyl enediynes V and VI, which also undergo iron dissociation upon photolysis, is also described. The light sensitivity of these six compounds is examined in detail with respect to previous work involving ferrocenyl enediynes by our group and others. In another area of enediyne chemistry, strained enediyne VII was heated to 37oC in the presence of halide salts (LiCl, LiBr, LiI) and found to generate halogen- substituted arene products VIII. This is a new reaction, never before explored. Extensive kinetic studies of this reaction are provided, a mechanism is proposed, and the implications thereof are discussed