Pyrazofurin synthesis

Although no recent activity has been reported in this field, it remains possible that more potent inhibitors of this enzyme have potential applications as anticancer therapeutics. It is also possible that the combination of salvage uridine-cytidine monophosphate synthesis inhibitors with inhibitors of de novo uridine-cytidine monophosphate synthesis (such as PALA or pyrazofurin) may result in more efficacious cancer therapeutics. 

Interest continues to be shown in the photodecomposition of diazonium salts,and aryldiazonium tetrafluoroborates have been recommended as potential photoaffinity labelling reagents for proteins.The key step in a recent synthesis of pyrazofurin involves the photodecomposition of the diazopyrazole (158) to give the hydroxypyrazole (159). ° 2-Azahypoxanthine (160) is the major... 

The first published synthesis of pyrazofurin was that accomplished by Farkas, Fleglova, and Sorm (72TL2279) by condensation of the C-ribofura-nosyl a-ketoester 45 with 1-benzylhydrazinoacetic acid to give the corresponding hydrazone 248, followed by cyclization, amidation, and debenzyla-tion to 7 (Scheme 55). 

Further data concerning the mechanism of action of 2-g-D-ribofuran-osylthiazole- carboxamide 2 (tiazofurin), in comparison with ribavirin and pyrazofurin have appeared. Marked inhibition of DNA and RNA synthesis by 2 was noted. Synthesis of the selenium analog of 2 was also reported. This compound, 3, was <5 fold more potent than 2 in cell tissue culture (P388, L1210 cells) and showed good Lewis Lung Carcinoma (LLC)... 

The synthesis of pyrazomycin (pyrazofurin) (33) from the corresponding 4-amino-5-cyano-3-ribofuranosyl-pyrazole has been reported. The biosynthesis of pyrazomycin and formycin has been investigated using a mixture of [5- H]-ribose and [l- C]ribose as substrates with S. candidus intact and specific incorporation of ribose into pyrazomycin was demonstrated from n.m.r. analysis of the labelled product, and a similar route for formycin was strongly suggested. 

The synthesis of pyrazofurin A (the 4-hydroxy analogue of (17)) and its a-anomer pyrazofurin B by a Wittig condensation on a ribose derivative is mentioned in Chapter 3 (ref. 183). Further references to antibiotic C-nucleosides occur in Chapter 18. C-Nucleosides of indoles have been prepared by glycosylation using ribosyl chloride derivatives. ... 

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