Bleomycin chemistry

A. Umezawa, H. Natural and Artificial Bleomycins Chemistry and Antitumor Activities. Pure and Applied Chem. 28, 665 (1971). 

Petering, D. Xiao, J. Nyayapati, S. Fulmer, P. Antholine, W. Oxidation Damage by Bleomycin, Adriamycin and Other Cytotoxic Agents that Require Iron or Copper Farrell, N., Ed. The Royal Society of Chemistry Cambridge,... 

Bleomycin A2 (32) is a complex molecule, and its synthesis involves many steps 7-10 To conform to space limitations, in this description of bleomycin synthesis coverage will be limited to key reactions exhibiting innovative chemistry or important stereochemical outcomes. 

Since H202 is easier to handle than 02, we will focus on the use of the former. Many metals can be used for this transformation [50]. Among them, iron compounds are of interest as mimics of naturally occurring non-heme catalysts such as methane monooxygenase (MMO) [51a] or the non-heme anti-tumor drug bleomycin [51b]. Epoxidation catalysts should meet several requirements in order to be suitable for this transformation [50]. Most importantly they must activate the oxidant without formation of radicals as this would lead to Fenton-type chemistry and catalyst decomposition. Instead, heterolytic cleavage of the 0—0 bond is desired. In some cases, alkene oxidation furnishes not only epoxides but also diols. The latter transformation will be the topic of the following section. 

Absalon MJ, Krishnamoorthy CR, McGall G, Kozarich JW, Stubbe J (1992) Bleomycin mediated degradation of DNA-RNA hybrids does not involve C-1 chemistry. Nucleic Acids Res 20 4179-4185... 

Dabrowiak JC (1980) The coordination chemistry of bleomycin a review. J Inorg Biochem 13 317-337... 

Rashid R, Langfinger D, Wagner R, Schuchmann H-P, von Sonntag C (1999) Bleomycin vs. OH-radi-cal-induced malonaldehydic-product formation in DNA. Int J Radiat Biol 75 110-109 Razskazovskiy Y (2003) Radiation-activated nuclease activity of o,o -diphenyleneiodonium cations (DPI) a reductively initiated chain reaction involving the Cl chemistry. Radiat Res... 

Drugs, such as bleomycin, aclacinomycin and deoxyspergualin, were discovered by the Umezawa group at the Institute of Microbial Chemistry in Japan and developed in collaboration with the NCI a number of the agents currently in advanced precUnical development at the NCI, such as UCN-01, and quinocarmycin and spicamycin analogs (Fig. 4), are the result of collaborations between Japanese companies, such as Kyowa Hakko Kogyo, Fujisawa Pharmaceutical Co. Ltd, and IQrin Brewery Ltd, and the NCI. ... 

Rather than discuss other anticancer examples in this chapter, interested readers are referred to a book with data on recent advances in the medicinal chemistry of such agents, including the anthracyclines, the bleomycins,the... 

Moreover, Sumio Umezawa had broad interests in the chemistry of other sugar-containing antibiotics. Bleomycins are useful antitumor agents discovered by Hamao Umezawa and co-workers in 1966 and are glycopeptides composed of a novel hexapeptide, a terminal amine, and a disaccharide. Collaboration with Hamao s group led to elucidation of the stmctnre of the disaccharide portion common to the bleomycins. For this work Shoji Omoto (Meiji Seika Kaisha) received his Ph.D., and Umezawa, with Tsuchiya and Miyake, synthesized the disaccharide. Later, he and co-workers successfully achieved the first total synthesis of bleomycin A2 in collaboration with the groups of Hamao Umezawa and Masaji Ohno (Professor of the University of Tokyo). 

Uller E, Demleitner B, Bemt I, Saalfrank RW (2000) Synergistic Effect of Serendipity and Rational Design in Supramolecular Chemistry. 96 149-176 Umezawa H, Takita T (1980) The Bleomycins Antitumor Copper-Binding Antibiotics. 40 ... 

Chemistry at the 4 -position of 2 -deoxyribose has been extensively studied due to the availability of reagents producing radical formation at this site (bleomycin, calicheamicin, peroxynitrite, and Fe2+-EDTA) [25-28]. 4 -Free radical formation... 

Although the coordination and orientation of the metal complex are still not understood, extensive studies have been conducted concerning the remarkable chemistry of this species. The overall mechanism of action is described in Figure 8.19. In the presence of oxygen, the Fe(II) O2 species is formed and is likely rapidly converted to a ferric superoxide species. The one-electron reduction of this species, using either an organic reductant or another equivalent of Fe(II)-bleomycin, leads formally to an Fe(III)-peroxide, which then undergoes... 

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