Pyrazofurin

The syn-anti conformational problem of a- and /3-pyrazofurins (756 one of the rare naturally occurring pyrazole compounds, see Section 4.04.4.4.3), which involves a rotation around a pyrazolic sp carbon atom and a sugar sp carbon atom, has been studied theoretically using the PCILO method (81MI40403). In agreement with the experimental observations, the /3 anomer is energetically more favourable than the a anomer, the preferred conformations being anti and syn, respectively. 

In this fashion, an a-ketoester was utilized as a means of studying the antiviral and antitumor activity of thiophene derivatives of pyrazofurin 14." Reactions between dimethylthiodiglycolate and 15 provided intermediate 16, which was elaborated to 17 and 18 for comparisons with the antitumor activity of the C-nucleoside pyrazofurin 14. 

The complex substitution of 1,4-dinitropyrazoles to afford 4-nitro-3(5)-substituted pyrazoles has been used to prepare the antibiotics formycin and pyrazofurin (91JCS(P1)1077). 

Scheme 6 Formation of pyrazofurin (24) and oxazinomycin (26) from labelled acetates...

The triazole ribofuranoside ribavirin (101) has been used clinically against influenza, parainfluenza and herpes infections with varying results, and imidazole ribofuranosides are active in vitro. The antibiotic pyrazofurin (102) inhibits the replication of many viruses and has also been tried as an anticancer drug. 

The naturally occurring nucleoside antibiotic pyrazofurine, CsiHnNsOs (38), shows broad-spectrum antiviral activity and a broad safety margin against boili RNA and DNA viruses in vitro. 

These compounds are inferior to pyrazofurin [97AHC(68)223] as antitumor agents against P388 and L1210 leukemia cells or Lewis lung carcinoma (85JOC1741) (Scheme 148). 

Considering the number of naturally occurring C-glycosides known, we cannot ignore the specific class of C-nucleosides. This class of compounds is particularly important due to the antibacterial, antiviral, and antitumor properties of many of these molecules. Some examples of naturally occurring C-nucleosides are shown in Figure 1.3.6 and include pyrazofurin, showdomycin, oxazinomycin, formycin, and formycin B.17>18... 

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. 

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