4-Amino-3-(2,3,5-tri-O-benzyl-beta-D-ribofuranosyl)-5-pyrazole-carb oni trile. Synthesis and conversion into a sugar-blocked 5,7-disubstituted formycin analog.
The title compound, a potential intermediate to protected C-nucleoside analogs related to formycin A, was synthesized via a new route wherein 2,3,5-tri-O-benzyl-1-O-p-nitrophenyl)-D-ribofuranose was converted to 2,5-anhydro-3,4,6-tri-O-benzyl-D-allonic acid, and further transformed into 4-(tert-butyloxycarbonyl)-5-ethoxycarbonyl-3-(2,3,5-tri-O-benzyl-beta-D- ribofuranosyl)pyrazole. After amidation and dehydration to form the 4-(tert-butyloxycarbonyl)-5-pyrazolecarbonitrile, acidolysis followed by a Curtius-type sequence afforded the 4-amino-5-pyrazole-carbonitrile nucleoside. Treatment of the latter with nitrous acid and copper chloride in a Sandmeyer-type reaction gave a diazonitrile rather than a chloronitrile. Attempts to convert either the aminonitrile or the diazonitrile to 5,7-diamino-3-(2,3,5-tri-O-benzyl-beta-D-ribofuranosyl)pyrazolo[4,3-d] pyrimidine (5-aminoformycin A) by condensation with guanidine or N,N-dimethylguanidine were unsuccessful. Condensation of the aminonitrile with carbon disulfide in pyridine provided access to the formycin system in the form of 3-(2,3,5-tri-O-benzyl-beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine-5,7 - dithione.
Rosowsky
A
A
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Ghoshal
M
M
Solan
V C
VC
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D005573:Formycins / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009705:Nucleosides; D011720:Pyrazoles; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D005573:Formycins; D007202:Indicators and Reagents; D009705:Nucleosides; D011720:Pyrazoles; C056882:5-aminoformycin A; C056881:4-amino-3-(2,3,5-tri-O-benzyl-beta-ribofuranosyl)-5-pyrazole carbonitrile