A new antimitotic substance, FR182877. III. Structure determination.

During the course of screening for novel cell cycle inhibitors, FR182877 was isolated from the fermentation broth of Streptomyces sp. No.9885. During the NMR measurements, FR182877 decomposed so much that the structure elucidation of FR182877 itself was difficult. Then, combinations of chemical correlations and spectroscopic methods clarified that FR182877 possesses an unprecedented multi-ring system including the strained double bond, which was unexpectedly epoxidized by molecular oxygen. FR182877 showed broad antitumor activities in vitro and promoted assemblies of tublins in vitro as well as taxol. It is noteworthy that epoxidation of the distorted double bond resulted in significant decrease in antitumor activities.