Calculations, synthesis, and kinetics of a series of cyclic rings containing a 1,5-diyne-3-ene unit; synthesis and reactivity of a water-soluble cyclodeca-1,5-diyne-3-ene; studies intopH-dependent DNA alkylating agents
Abstract
Computational studies were carried out to develop a hypothesis for the occurrence of room temperature Bergman reactions. This hypothesis was then tested by the synthesis and kinetic study of a series of cyclic molecules containing an enediyne unit. The results showed that for simple cases the hypothesis was valid. Further work into these cyclic enediynes, led to the synthesis and study of a cyclic enediyne diol, 1, as a potential DNA cleaving agent. The synthesis of this molecule was performed in twelve steps with 3.2% overall yield. Studies then showed that the molecule was able to affect DNA strand scission efficiently, through the probable intermediacy of a para-benzyne diradical.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) Work was also performed in order to elucidate the mechanism of DNA strand scission by bis propargylic sulfones. Although, at first, the mechanism was thought to involve a diradical species, further investigation showed that the strand scission goes by way of alkylation of the DNA. Part of these investigations involved the synthesis and study of a number of sulfones.
Subject Area
Organic chemistry
Recommended Citation
Zuccarello, Guido, "Calculations, synthesis, and kinetics of a series of cyclic rings containing a 1,5-diyne-3-ene unit; synthesis and reactivity of a water-soluble cyclodeca-1,5-diyne-3-ene; studies intopH-dependent DNA alkylating agents" (1990). Dissertations available from ProQuest. AAI9026676.
https://repository.upenn.edu/dissertations/AAI9026676