Enediyne mechanism studies

The previously known kedarcidin chromophore (7) is revised to CCC (7559), and the mechanism of action of this enediyne has been studied (1560). The new maduropeptin chromophore 1601 was isolated from Actinomadura madurae, which is associated with a protein of 14 amino acids (1561-1563). The non-protein associated enediyne N1999A2 (1602) was characterized from Streptomyces sp. AJ 9493 (1564), and confirmed by synthesis (1565,1566). 

Because of the DNA-cleaving ability and antitumor properties of such naturally occurring diyl precursors as calicheamicin, there has been a great deal of study directed toward the mechanism of diyl formation [32]. The rate of diradical formation has been found to depend on many factors, including (1) the distance between the two alkyne subunits (2) concentration of the trapping agent (3) substituent effects and (4) the difference in strain energy between the enediyne and the cycliza-tion transition state. 

Work in this area has been dominated by studies on the enediyne class of anticancer antibiotics which bind to the minor groove and cleave DNA through the generation of a diradical intermediate. A genoul review on the chemistry and mechanism of action of these antibiotics has appeared together with two more focused reviews on neocarzinostatin (2S7) and the... 

This useful synthetic methodology can be applied for the construction of not only the triarylethene framework but also CF3-containing enediyne derivatives, which can be used to study the mechanism for their function in antitumor antibiotics, such as dynemicin, neocarzinostatin, and esper-amicin as well as to synthesize oligoenynes, oligoene-diynes, and / -conjugated polymers for electronic and photonic applications. As shown in Scheme 26.58,... 

Many of these reactions have attracted the attention of researchers due to the fact that these processes occur in the body during the application of anticancer drugs containing an enediyne block. Chapter 3 is devoted mainly to the analysis of papers related to the study of the cyclization mechanism. Chapter 4 includes additional material on cycloaddition with acetylenic units or those sourced from acetylenic compounds, leading to the formation of carbo- and heterocycles of different structures. The concluding Chapter 5 includes some recent results. 

To reveal a better understanding of the reaction mechanism, the effect of the amino group on the formation of 2,3-dihydrobenzo[/] isoindoles was studied including the importance of the structure of the amino acid side branch. The results showed that amino acids with different side chains alter considerably the reactivity of the very unstable enediyne system, as seen from the comparison of the data of DSC. 

The mechanisms of action of the enediyne systems and their design have been studied since the time of their discovery, but along with these... 

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