Designed enediynes

In spite of the fact that few cycloalkynes occur naturally, they gained recent attention when it was discovered that some of them hold promise as anticancer drugs. (See the boxed essay Natural and Designed Enediyne Antibiotics following this section.)... 

Nicolaou KC, Smith AL, Yue EW. (1993) Chemistry and biology of natural and designed enediynes. Proc Natl Acad Sci USA 90 5881-5888. 

Jones GB, Fouad FS (2002) Designed Enediyne Antitumor Agents. Curr Pharm Design 8 2415... 

Another important feature of designed enediyne prodrugs is the presence of attachment points to be used for joining DNA-complexing substructures. The dramatic importance of the delivery unit in calicheamicin indicates that it is probably very difficult to achieve nanomolar potencies without a fitting DNA-complexing agent. 

Nicolaou, K.C. Liu, A. Zeng, Z. McComb, S. Redox-controlled Bergman cycloaromatizations. Designed enediynes with DNA-cleaving properties and antitumor activity. J. Am. Chem. Soc. 1992, 114, 9T19-91 1. 

Scheme 7-7S Designed enediynes with novel triggering devices and tempered reactivity (Nicolaou et al.).

Table 7-5 Cytotoxicities of designed enediyne 357 against a panel of 21 tumor cell lines (top group) and four normal cell lines (bottom group)...

Table 7-6 Cytotoxicities (IC50/M) of designed enediynes containing [>-sulfone triggers (Nicolaou et a/.)...

Nicolaou KC, Stabila P, Esmaeli-Azad B, Wrasidlo W, Hiatt A (1993) Cell-specific regulation of apoptosis by designed enediynes. Proc Natl Acad Sci U S A 90 3142-3146... 

Based on 38 and the results from other laboratories involving diaryl enediynes, we wished to design enediyne systems where alkyne termini could be derivatized with variable functionality, and the photoactivity of the Bergman cycloaromatization could be tuned both in terms of electronics and strain energy. Specifically, since most photoactivated enediynes studied to date have the vinyl moiety embedded in an arene, we wished to design a family of differentially capped alicyclic enediynes 41 and investigate their photochemical activation to diyls 42 as a function of these effects (Scheme 11). 

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