A new route to 10-membered ring analogues of neocarzinostatin chromophore

✍ Scribed by Thomas Wehlage; Adolf Krebs; Thorsten Link

• Publisher: Elsevier Science
• Year: 1990
• Tongue: French
• Weight: 226 KB
• Volume: 31
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)97131-4

✦ Synopsis

l7le synthcse of new I&d& cyc~ne co?npo& neoc&statin chrmwphore 1 by innmnolcculor aihl type cycl~m are described. doted to During the past two years the highly unusual structures of cycloaknediyne antibiotics such as neotxzinostatin chromophore (NCS Chrom),' eqeramicin, za calicheamicin %nddynemicinA,3 have attracted considerable atta~tion due to their outstanding biological activity. NCS Chrom, the most strained member in this series, consists of a structurally unprecedented epoxybicyclo[7.3.O]dode&@x&yne system. 4 The proposed mechanism of DNA damage by NCS Chrom is based on binding to double stranded DNA via interc&tion of its naphthoate moiety into the minor groove. Upon nucleophilic activation with thiol, NCS Chrom generates a highly reactive biradii which abstracts a hydrogen from C-5' of the DNA backbone to produce DNA strand breaks under aerobic conditions (Pathway A). 5 Very recently Hii and coworkers suggested an alternative mode of cyclization to form the biological active biradical under anaexobic conditions (Pathway B) 6 shown in Scheme 1. scheme 1 0 -'0