Formycin 7- -, preparation

The formycin analog 902 was prepared from 901 (84JHC505). It was inactive against HSV-1 and HSV-2. 

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). 

In a similar manner, the / -D-xylofuronoxyl analogue could be prepared <84T119, 86JCS(P1)1267>. Several other derivatives of formycin have been prepared from C-glycosylaminopyrazole carboxylic acids <8iMi 712-01). 

Formycin B (528) is prepared from the pyrazole (529) by treatment similar to that reported for the synthesis of formycin A (54a) from (523) (72CCC2786). 

Figure 10.13 HPLC of FoA and its metabolites produced by activities present in an S-30 fraction prepared from rat liver FoB is a formycin analog of inosine. Operating conditions mobile phase, 0.1 M KH2P04 adjusted to pH 5.5 with NaOH with 10% methanol flow rate, 2 mL/min room temperature Qg /xBondapak column packing fluorescence, excitation at 300 nm, emission about 320 nm. (A) Chromatogram obtained with standards as indicated at approximately 10 /xg of each. Sensitivity of fluorescence detection, 0.5 AUFS units full scale. (B) Chromatogram obtained immediately after addition of S-30 to a reaction mixture containing FoA and ATP. (C and D) Chromatograms obtained after 8 and 16 minutes of incubation, respectively. [From Dye and Rossomando, 1982. Reprinted by permission from Bioscience Reports, 2 229-234 (1982).]...

Formycin B (387) was prepared [71JCS(CC)986] from the 5-carbam-oyl-4-hydrazinocarbonyl-3-/3-D-ribofuranosylpyrazole 407 (70TL4611 ... 

Many modifications were performed on the heterocyclic system of for-mycin and formycin B, which included the preparation of 451-453... 

Formycin and formycin B with modified sugar subunits have also been prepared using, mostly, the nucleoside-nucleoside approach. In one instance, however, 2 -deoxyformycin B (458) was prepared by regio- and stereospecific palladium-mediated C—C bond formation between the fu-ranoid glycal 454 and protected 3-iodopyrazolo[4,3-d]pyrimidine. The C-nucleoside 455 having an unsaturated sugar moiety was subsequently elaborated to 458 (92JOC4690) (Scheme 125). 

Deoxyformycin (463) was prepared as a sole product from formycin (386) by protection of 03 and 05 followed by introduction and reductive removal of a 2 -0-phenoxythiocarbonyl group (85JMC1096 89MI3) (Scheme 127). 2 -Deoxyformycin B was also prepared from formycin B according to the latter route (89MI3). 

The acyclo analog of formycin B 496, however, was synthesized by annula-tion of the pyrimidinone ring onto the pyrazole ring of 494, as explained in Scheme 134. Acyclo analogs of formycin and 5-aminoformycin B were also prepared according to this approach [85JCS(P1)2087). 

The most commonly used strategy for the synthesis of this class of C-nucleosides was the annulation of the 1,3,5-triazine ring onto suitably substituted pyrazol-4-yl C-nucleosides. Thus, the C-nucleosides 836, related to adenosine and formycin, was prepared by reacting the 3-aminopyrazol-... 

Prepared by similar reactions was the 8-()3-D-ribofuranosyl)pyrazolo[l,5-a]l,3 5-triazin-4-one (840) related to inosine and formycin. In one route 832 reacted with iV-ethoxycarbonylformimidate (76JHC1305), and in the other the 3-amino-2-carbamoylpyrazol-4-yl C-nucleoside 839 reacted with triethyl orthoformate (80JHC1435) or l,3-dimethyl-l,3,5-triazine-2,6-dione in the presence of sodium ethoxide (86JHC349) (Scheme 219). 

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