Enediyne compound

Gredicak, M., Jeric, I. Enediyne Compounds New Promises in Anticancer Therapy. Acta Pharm. 2007, 57, 133-150. 

Finally, a not trivial issue is the stability in the dry state. It is actually known that, often, enediyne compounds tend to undergo radical polimer-ization in the dry state. It is clear that, for potential development as a drug, full stability is essential. 

Nicolaou, K.C. Dai, W.-M. Wendebom. S.V. Smith. A.L. Torisawa, Y. Maligres, P. Hwang, C.-K. Enediyne compounds equipped with acid-, base, and photo-sensitive triggering devices. Chemical simulation of the dynemicin A reaction cascade. Angew. Chem., Int. Ed. Engl. 1991. 30. 1032-1036. 

Unno, R. Michishita, H. Inagaki. H. Baba. Y. Jomori, T. Nishikawa, T. Isobe, M. Synthesis and biological evaluation of novel cyclic enediyne compounds related to dynemicin A as antitumor agents. Chem. Pharm. Bull. 

Xi Z, Goldberg IH. DNA-damaging enediyne compounds. In Kool ET, ed. Comprehensive Natural Products Chemistry. Amsterdam Elsevier 1999 553—592. 

Expanded details of an earlier paper (see Vol. 26, p. 155, ref 10) on the preparation of a sugar enediyne compound has been reported. ... 

The delicate enediyne compound 45 has been obtained from a Streptomyces globosporus Cl027 broth filtrate. On treatment with such mild reagents as methanol or dioxane it aromatizes to give compound 46 which has been analysed by n.m.r. methods. The absolute configuration was not determined. ... 

Xi, Z. and Goldberg, I.H. (1999) DNA-damaging enediyne compounds, in Comprehensive Natural Products Chemistry, vol. 7 (eds D.H.R. Barton, K. Nakanishi and O.Meth Cohn), Pergamon Press, New York, pp. 553-592. 

Beginning in the 1980s, research directed toward the isolation of new drugs derived from natural sources identified a family of tumor-inhibitory antibiotic substances characterized by novel structures containing a C=C—C=C—C=C unit as part of a nine- orten-membered ring. With one double bond and two triple bonds (-ene + di- + -yne), these compounds soon became known as enediyne antibiotics. The simplest member of the class is dynemicin A most of the other enediynes have even more complicated structures. 

Upon heating the enediyne la rearranges reversibly to the 1,4-benzenediyl diradical 2a, which in its turn can rearrange to the enediyne lb or—in the presence of a hydrogen donor (e.g. cyclohexa-1,4-diene)—react to the aromatic compound 3a. 

The chemistry of enediynes, enyne allenes and related compounds ... 

The anticancer activity of complex natural products having a cyclodecenediyne system [for a review see <96MI93>] has prompted the synthesis of 54 (X = CH2 and OCH2) <96CC749> and 55 (R = a-OH and p-OH) <95AG(E)2393> on the basis that such compounds are expected to develop anticancer activity as the P-lactam ring opens. This is because cycloaromatization can only occur in the monocyclic enediyne and the diradical intermediate in the cyclization is thought to be the cytotoxic species. 

Many compounds that damage DNA via radical intermediates have been identified. Some of the agents, such as bleomycin and the enediynes, damage DNA primarily through abstraction of hydrogen atoms. ° In these cases, chemical reactions are directed to certain positions on the DNA backbone by noncovalent binding that places the reactive intermediates in close proximity to particular deoxyribose sugar residues. Similar to the reactions of HO described above, small radicals, such as... 

The Pd°-catalyzed transformation of enediynes represents a highly efficient and effective approach for the synthesis of polycyclic compounds, with different ring sizes being obtained by a variation of the tether [129]. In this respect, reaction of 6/1-270 led to the tricyclic product 6/1-271 as a single diastereomer. The initial step is a chemoselective hydropalladation of the propargylic ester moiety in 6/1-270 to give an alkenyl-Pd-species, according to the mechanism depicted in Scheme 6.71. A hexatriene is formed as a byproduct. 

A general synthetic route to p-lactam-fused enediynes (Scheme 2.321) has been successfully developed (848). When nitrone (771) was subjected to Kin-ugasa reaction conditions, two p-lactam containing products were obtained the elimination product (772) and the trans fused compound (773). 

To date, few carbohydrate interactions with DNA have involved interactions within the major groove. Among the classes of compounds known to exhibit DNA binding are enediyne antibiotics, anthracydines, pluramycins, indolocar-bazoles, and aureolic acids. Of the limited number of carbohydrates known for DNA binding, only a select few have displayed major groove contacts. These... 

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