Blasticidin synthesis

T. Kondo, H. Nakai, and T. Goto, Synthesis of cytosinine, the nucleoside component of antibiotic blasticidin S, Tetrahedron, 29 (1973) 1801-1806. 

There are numerous examples of the inhibition of biosynthesis by fungicides. Some fungicidal secondary metabolites, like cyclohexi-mide and blasticidine, interfere with synthesis of peptide bonds at the ribosomal site (2). Another, kasugamycine, influences aminoacyl-t-RNA/ribosome interactions (3). Finally, another mechanism inhibiting protein biosynthesis is realized on the DNA/RNA- level by the... 

The activity of blasticidin S involves primarily the inhibition of fungal protein synthesis. In the presence of blasticidin S, the incorporation of amino acids into protein is reduced by 80-90% (Gottlieb et al., 19SS Misato et al., 1%1 Huang et al.. 1964a). It was foimd that blasticidin S reduces the formation of aminoacyl-tRNA. Hence the next step, the incorporation of the amino acid, is also block. The site of primary action is not yet known. 

The mode of action of kasugamycin is similar to that of blasticidin S. It inhibits protein synthesis in fungi and bacteria. It inhibits binding of the aminoacyl-tRNA complex to the ribosome (Tanaka et al., 1966), but does not disturb the synthesis of nucleic acids. The inhibitory effect is considerably lower in the liver tissue of rats. The selectivity of toxicity may be due to the particular sensitivity to kasugamycin of the ribosomes of each type of organism. This may also explain the relatively rapid development of resistance to kasugamycin. 

Diels-Alder reactions of glyoxylates have recently found application in natural product total synthesis. For example, Schmidt and Wagner used such a cycloaddition as a key step in synthesis of uracinine derivative 3, a component of the nucleoside antibiotic blasticidin S (Scheme 4-II).13 Interestingly, when unsymmetrical diene 1 undergoes [4 + 2] cycloaddition with a glyoxylate, only one series of regioisomers is produced, which has the incorrect orientation for synthesis of 3.14 However, if the o-benzoyl... 

The Fukuyama amine synthesis has seen wide application in the context of natural product synthesis. Complex polyamine natural products that highlight the orthogonal nature of the nosyl protecting group, such as lipogrammistin-A12 and various spider toxins,13 have been efficiently synthesized. This protocol has also been used in the context of medicinal chemistry,14 glucosylamines,15 and blasticidin amino acids.16... 

Although blasticidin S has played a major role in the control of P. oryzoe infections of rice, it is toxic to this plant at higher concentrations (118). Blasticidin S has been used to study plant protein synthesis under a variety of stress conditions. Examples include effects on the production of the [4rytoa1exin glyceollin, and related compounds, in soy-bean (119,120), of furanoterpenes in sweet potato (121), and of avenalumin in oats (122). 

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