ORGN 29 |
| Edyta M. Brzostowska and Alexander Greer. Department of Chemistry and The Graduate Center, The City University of New York (CUNY), Brooklyn College, Brooklyn, NY 11210 |
| This study represents an effort to explore the mechanism of sulfur bond-making and bond-breaking of varacin and other pentathiepin natural products. The naturally-occurring polysulfanes varacin and calicheamicin exhibit antitumor antibiotic activity and give rise to DNA cleavage. An interesting aspect is that both natural product polysulfanes possess an amine functionality that provides an enhancement of the bioactivity. Without these amine attachments the biological activities are decreased. Evidence suggests that breakdown of pentathiepin is of importance in S-S cleavage and the generation of an activated sulfuration fragment, S3, which may control the toxic effects of the natural product varacin. Potential parallels were considered between the polysulfanes varacin and calicheamicin and much is known about 1,4-didehydroarene (p-benzyne) biochemistry in the enediyne class of antitumor agents. The biochemical reactivity of p-benzyne is established; however, the production of o-benzyne in vivo remains unknown. A benzyne-pentathiepin reaction immediately came to mind and we present work in this area. Based on information from mechanistic studies we suggest an inability for pentathiepin to decompose to yield 1,2-didehydroarene (o-benzyne) and believe it can be ruled out. The intermediacy of o-benzyne was studied with the idea that some marine organisms developed chemical pathways to use elemental sulfur in small molecule biosynthesis. Pentathiepins are proposed to be developed by some organisms from dopamine precursors. A new concept is presented here that connects aspects of o-benzyne chemistry to factors related to the biogenesis of pentathiepin natural substances. Since biochemical studies have established the existence of p-benyzne, we thought that a physical-organic study could add confidence to the suggestion that dopamine may lose hydrogen to yield 1,2-didehydroarene, which serves as an acceptor of sulfur to generate varacin. |
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Physical Organic Chemistry: Calculations, Mechanisms, Photochemistry and High Energy Species
8:00 AM-12:00 PM, Sunday, September 7, 2003 Sheraton New York -- Royal Ballroom A, Oral
Division of Organic Chemistry |