Tautomerism formycin

Steady-state and time-resolved emission spectroscopy was used to study the interaction of E. colt PNP with its specific inhibitors formycin B, FA, and A -l-methylformycin A. Complexation was found to induce tautomeric shifts <2000BBA1467>. Carbocyclic analogues of formycin A and B have been recently synthesized <2004T8233>. The synthesis utilized 417 as starting material which was converted into 418 via a multistage synthesis. The latter could be converted into the formycin analogue (Scheme 36) <2004TL8233>. 

The luminescence spectra of formycin (190) and its aglycone and various N-methyl derivatives at room temperature and at 77 K indicated that they consist of two tautomeric species, N(1)H and N(2)H, both of which emit at 300 hm at 77 K. They can be distinguished by location of emission maxima. Photolysis induced tautomerism (82MI2). 

The tautomeric equilibrium between IH- and 2//-formycin (7-amino-3)8-D-ribofuranosyl-l//-pyrazolo[4,3-d]pyrimidine) has a constant ratio N(2)H/N(1)H = 0.2 and an enthalpy difference estimated at 1 kcal mol". The tautomeric interconversion is catalyzed by (3 x 10 Msec" ) and by OH" (5 X 10 M" sec" ). No other catalytic pathway such as water catalysis or tautomerization via tautomeric cations contributes significantly to the interconversion. Protonation on the pyrazole ring of formycin does not occur significantly (80JA3897). 

Luminescence spectra of formycin B (88b), its aglycone (88c) and various N-methyl derivatives at room temperature and at 77K indicated that they consist of two tautomeric species (88) and (89) both of which emit at 300 nm at 77K. They can be distinguished by location of emission maxima <82MI 712-02). Photolysis induced tautomerization <82Mi 712-02). The tautomeric equilibrium between (88c) and (89c) has a constant ratio [Ar(2)-H/A(l)-H = 0.2] and the energy difference in ethanol is estimated to be 1 kcal mol-1. The tautomeric interconversion is catalyzed by H+ (3 x 109 M-1 sec-1) and by OH- (5 x 105 M-1 sec-1). No other catalytic pathway such as water catalysis or... 

The dynamic tautomerism of formycin A (54a) was investigated by a temperature jump method and the mechanism of tautomerism discussed (78JA3957). 

Deoxy- and 5 -deoxy-5 -halo-derivatives of pseudo-uridine(5- 5-D-ribo-furanosyluracil) have been prepared by conventional methods, with the 5 -fluoro-derivative being prepared from 2, 3 -0-isopropylidene-pseudo-uracil by reaction with 7V,A -diethyl-iV-(2-ehloro-l,l,2-trifluoroethyl)amine as a less conventional fluorinating reagent. Other papers report on the five possible A -monomethyl formycins and the tautomeric equilibrium between the 7- and 8-protonated forms of formycin (25). Further references to antibiotic C-nucleosides are made in Chapter 18. 

The relationship between the rate of tautomeric equilibrium of formycin and its enzymic reactions has shown that the former is faster so that the rate of any process which is specific to the minor tautomer is not limited by the rate of tautomerism. Several references to C-bonded nucleosides appear in Chapter 3. 

The C n.m.r. spectra of formycin, formycin B, and certain pyrazolo[4,3-f/]-pyrimidines have been examined in DMSO and HMPT, and as a function of temperature, in order to probe the prototropic tautomerism of the pyrazole portion of the heterocyclic system. Only the 1-NH % 2-NH prototropic process was observed, and the proportion of the 2-NH tautomer (a higher energy species than the 1-NH tautomer) was shown to depend on the substituent present at C-7 of the pyrimidine portion of the heterocyclic system. 

The use of C n.m.r. spectroscopy in elucidating the structures of monosaccharides, polysaccharides, nucleosides, and nucleotides has been reviewed. A study of the tautomerism of formycin and related compounds using C n.m.r. spectroscopy is noted in Chapter 21. ... 

The tautomerism in adenine is displaced towards the canonical amino form both in the gas phase and in solution, and the population of the imino tautomer is too small to play any significant biological role. A different situation occurs for analogs of adenine such as 6-aminopyrazolopyrimidine. The ribo-derivative of this compound (formycin) has very interesting chemotherapeutic properties, and it can be recognized in place of adenine in many biological processes, including incorporation in DNA [110-112]. 

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