The structures of crystalline fervenulin, 2-methylfervenulin-3-one (MSD-92), and their 4-N-oxides were studied using x-ray diffraction and 1 H and 13 C NMR spectroscopy techniques. A comparative analysis of the spectroscopic data and the chemical reactivity of pyrimidotriazine antibiotics and their analogs allowed the reactive centers of these biologically active compounds, ways of their activation, and mechanisms of transformation to be elucidated.As is known, 3-substituted derivatives of the antibiotic fervenulin exhibit transformation into xanthine [1] and azauracil [2] derivatives as a result of the nucleophilic attack of formamide at C-8a, and of OH ion at the C-5 atom of the pyrimidotriazine nucleus, respectively. On heating with indoles in the presence of acids, fervenulin attaches the indole moiety at the C-4a atom with the formation of stable indolyl derivatives [3]. However, fervenulin 4-N-oxide reacts with nucleophiles in a different manner. For example, the interaction of this oxide with CH acids (acetylacetone, dimedone, and acetoacetic, malonic, cyanoacetic, and nitroacetic esters, etc.) in anhydrous DMSO in the presence of triethylamine at 20 -25°C leads to a high yield of the corresponding derivatives of 1,3-dimethyl-5-nitroso-6-hydrazinouracil [4,5].Thus, the available experimental data indicate that the presence of a 4-N-oxide function in the fervenulin nucleus leads to a dramatic change in the reactivity of pyrimidotriazines. However, there are almost no data on the structure of 4-N-oxides and their spectral characteristics, although this information would be useful for the identification and char-acterization of reactive centers, ways of their activation, and mechanisms of chemical transformation of these compounds.In order to fill this gap, we have synthesized crystals of 4-N-oxides of fervenulin and 2-methylfervenulin-3-one and studied them by x-ray diffraction and 1 H and 13 C NMR spectroscopy techniques in order to elucidate the role of 3-oxoand 4-N-oxide groups in the reactivity of these compounds.The simplest pathway to the synthesis of fervenulin-4-oxide (V) is via the nitrosation of 6-hydrazinouracil I, followed by cyclization of the intermediate 5-nitroso-6-hydrazinouracil (IV) with ortho-formic ester (Scheme 1, path A) [6]. The disadvantages of this method are (i) multistage procedure, (ii) long synthesis time, and (iii) low yield of the target product. In order to avoid these drawbacks, we have previously developed a simple "one-pot" method for the synthesis of fervenulin-4-N-oxide (V) by means of the sequential treatment of the initial hydrazinouracil (I) in acetic acid solution with glyoxylic acid and sodium nitrite (Scheme 1, Path B) [7].Ichiba et al.[8] used fervenulin-4-oxide for the synthesis of fervenul-3-one (X) and its 2-methyl derivative (XI) (Scheme 2, path A). We oxidized fervenulin-4-oxide by gaseous chlorine in aqueous acetic acid solution [9] and obtained 4-N-oxide of fervenul-3-one (XII) (Scheme 2, Path B) 398 0091-150X/06/4007-0398

Experimental data on the chemical transformations of the antibiotic fervenulin and its analogs have been analyzed and compared to the results of recent physicochemical investigations. Crystals of donor -acceptor complexes of fervenulin and its 4-N-oxide with indoles have been obtained, their IR spectra have been studied, and their x-ray structure analysis was performed for the first time. Information concerning the reaction sites of the fervenulin molecule is obtained.