Chemistry of Natural and Photoswitchable Cyclic Enediynes

Abstract

The cyclic enediynes, a relatively new class of antitumor antibiotics are strong DNA cleavage agents and exhibit remarkable antitumor activities both in vitro and in vivo. Naturally occurring enediyne antitumor antibiotics are divided into two groups according to the 9- or 10-membered ring core structure. The first enediyne antibiotic, neocarzinostatin (NCS) consisting of 1:1 mixture of an apoprotein and a chromophoric molecule (shown inFigure 1.1), was isolated from Streptomyces carzinostaticus in 1965. However, the structure of the NCS chromophorewas determined twenty years later. Following the disclosure of the unprecedented molecular structure of neocarzinostatin, two families of 10-membered ring enediynes were discovered in 1987, as represented by calicheamicin from Micromonospora echinospora and esperamicin-A 1 from Actinomadura verrucospora.