Reexamination of some reactions of 3-(D-galactosylidenehydrazino)-1,2,4-triazino[5,6-b]indole.

Incorrect structures described in the literature for the products of reactions of the title compound 6 were reexamined and corrected. Thus, the product of acetylation of 6 with acetic anhydride in the presence of pyridine was found to be the mono-N-penta-O-acetyl derivative 10 and not the previously described di-N-penta-O-acetyl derivative 7. Assignment of structure 10 was based on 1H NMR data as well as its ability to undergo oxidative cyclization with Br2/AcOH to give 12. The previously assigned structure 7 would be incapable of undergoing such cyclization. The linear structure 12 rather than the angular regioisomer 3c was assigned on the basis of its UV absorption pattern and 1H NMR NOE spectra. Attempted preparation of 7 by increasing the duration of the reaction gave only compound 10. A di-N-acetyl-penta-O-acetyl derivative, however, was obtained with acetyl bromide in the presence of pyridine to which structure 8 rather than structure 7 or 9 was assigned on the basis of 1H NMR NOE studies. Acetylation of the triazolo-triazino-indole 11 gave a product identical to 12; structure 15 previously assigned to this product is, therefore, in error. Finally, the angular annelated structure 3e previously ascribed to the oxidative cyclization product of the 5-methylhydrazone congener of 6 (13) is now rectified to the linear annelated structure 14; the latter was found to be identical to the product obtained by N-methylation of the unequivocally linear 1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indole 11. Compound 8 was found to exist in the preponderantly populated sickle (bent) conformation 18 in contrast to compounds 10 and 12 which were found to adopt the extended planar zigzag conformations 19 and 20 respectively.

Reinvestigation of the regiospecific outcome of heterocyclization of 3-hydrazino-1,2,4-triazino[5,6-b]indoles: angular versus linear annelated 1,2,4-triazolo-1,2,4-triazino[5,6-b]indole structures.

Divergences of the structural assignments reported in the literature for the products of cyclization of 3-hydrazino-1,2,4-triazino[5,6-b]indoles 1 with one-carbon cyclizing reagents have been reinvestigated. The linear annelated 1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indoles 3 were found to be the products regiospecifically formed, rather than the angular annelated 1,2,4-triazolo[3,4-c]1,2,4-triazino[5,6-b]indoles 2. Our findings were based on comparison of the UV spectral data of the cyclization products with those of unequivocally as well as inevitably linear annelated compounds. Calculations of optimized geometries and electronic structures accord with the results obtained. Divergences reported in the literature were, therefore, attributed to erroneous structural assignments rather than to cyclization by different regiochemical pathways.

Synthesis and antimicrobial activity of acyclo C-nucleosides: 3-(alditol-1-yl)-7-oxo-5-phenyl-1,2,4-triazolo[4,3-a]pyrimidines.

Condensation of 2-hydrazino-4-oxo-6-phenylpyrimidine (1) with aldopentoses 2a-d or aldohexoses 2e-g gave the corresponding aldehydo-sugar (4-oxo-6-phenylpyrimidin-2-yl)hydrazones 3a-g which were acetylated to the corresponding poly-O-acetyl-aldehydo-sugar (3-acetyl-4-oxo-6-phenylpyrimidin-2-yl)hydrazones 4a-g. The latter compounds underwent oxidative cyclization with bromine in acetic acid and in the presence of sodium acetate to the corresponding 8-acetyl-3- (poly-O-acetyl-alditol-1-yl)-7-oxo-5-phenyl-1,2,4-triazolo[4,3-a]pyrimid ines 6a-g. Compounds 6a-g were also obtained by consecutive one-pot oxidative cyclization/acetylation in which the parent hydrazones 3a-g were treated with bromine/acetic acid/sodium acetate followed by acetic anhydride. Deacetylation of 6a-g with ammonium hydroxide in methanol gave the title compounds 7a-g. The antibacterial and antifungal activities of compounds 3c, 3f, 7c and 7f are reported.

Sterically controlled regiospecific heterocyclization of 3-hydrazino-5-methyl-1,2,4-triazino[5,6-b]indole to 10-methyl-1,2,4-triazolo[4',3':2,3[1,2,4-triazino[5,6-b]indoles.

3-Hydrazino-5-methyl-1,2,4-triazino[5,6-b]indole underwent sterically controlled regiospecific heterocyclizations with a variety of one-carbon cyclizing agents to give the sterically more favored linearly annulated 10-methyl-1,2,4-triazolo[4',3':2,3[1,2,4-triazino[5,6-b]indoles rather than the sterically less favored angularly annulated 10-methyl-1,2,4-triazolo[3',4':3,4]1,2,4-triazino[5,6-b]indoles. The assigned structures were corroborated by comparison with unequivocally synthesized authentics, chemical and spectral data. The antimicrobial activity of some of the prepared compounds was investigated.