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The glycosylation reaction of 6-nitroindoline with 5-tritylribose led to the synthesis of the 1-Β-D-ribofuranoside and 1-Β-D-ribopyranoside of 6-nitroindoline, the dehydrogenation of which resulted in the isolation of the corresponding 1-Β-D-ribopyranoside and 1-Β-D-ribofuranoside of 6-nitroindole; the last with protecting groups are suitable for utilization in oligonucleotide synthesis.

First O-glycosides of N-hydroxyindole were synthesized by the interaction of the indoles containing electron withdrowing substituents with acyl halogenoses in the presence of alkaline reagents. 1-O-beta-D-Glucopyranosides of 1-hydroxy-5-(or 6)-nitroindoles, 1-O-beta-D-ribofuranoside of 1-hydroxy-5-nitroindole and also 1-[(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)oxy]-2-methoxycarbonylindole were obtained. 1-[(2,3,4,6-Tetra-O-acetyl-beta-D-glucopyranosyl)-oxy]-6-nitro-indole was transformed into 1-[(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-oxy]indole.

Earlier interaction of indole-3-carbinols with L-ascorbic acid and chemical and biological properties of formed 2-skatylderivatives of L-ascorbic acid (ascorbigens) were discussed. In this presentation the properties and stereochemistry of products of interaction of polyfunctional biologically important indole-3-carbinols (indoleglycerol analogs and beta-hydroxytryptamine derivatives) with L-ascorbic acid are investigated. Biological significance of this reaction is discussed.

A method of synthesis of antibiotic streptonigrin 8'-O-alkyl ethers by alkylation of streptonigrin diphenylmethyl ester and consequent deprotection of carboxylic group with CF3COOH is developed. An attempt to deblock carboxylic group of 8'-O-methylstreptonigrin diphenylmethyl ester by hydrogenation over Pd produced 8'-O-methylstreptonigrone. Similarly streptonigrin was transformed into streptonigrone over Pd-black in H2 stream. Methylation of streptonigrone afforded 5',5'-N-dimethyl-2',8'-O-dimethylstreptonigrone and 1',5',5'-tri-N-trimethyl-8'-O-methylstreptonigrone. Alkyl streptonigrin ethers demonstrated lower antibacterial activity in vitro than the parent antibiotic.

The structures of previously obtained nucleosides of 5-substituted 4-chloro-1, 2,3-triazoles were refined by means of high-resolution mass spectrometry and 13C NMR spectroscopy. It is shown that fusion of 5-substituted 4-chloro,1,2,3-triazoles with tetra-0-acylribofuranoses in the presence of di(p-nitrophenyl) phosphate leads to the formation of 2-nucleosides of the corresponding triazoles. The signals of the carbon atoms in the 13C NMR spectra of the 4,5-di-substituted triazoles and their nucleosides were assigned.

The following review discusses major directions in the research and preparation of various classes of advanced antitumor agents: synthetic materials which work by an alkylating mechanism (derivatives of di (2-chloroethyl)amine, ethylenimine, alkylnitrosourea, dimethyltriazines); platinum derivatives; dispiropiperazines; alkylating agents derived from polyols; various antimetabolites; as well as compounds derived from natural products, such as anthracycline antibiotics, bleomycin, actinomycin, mitomycin, derivatives of aureolic acid, etc. Also discussed are the use of enzymes to destroy substances needed for tumor growth; new plant alkaloids which inhibit mitosis (Vinca alkaloids, Podophyllin toxins, colchamine, etc.); and immunomodulating agents.

The authors study the influence of anomeric 5-substituted 2'-dioxyuridines compounds I-XIV on the incorporation of labeled precursors into the DNA of ascites hepatoma 22A cells of C3HA mice in vitro and in vivo. In addition, the DNA of chicken fibroblasts, growing in a monolayer, before and after infection with herpes simplex virus was studied. The influence of the given compounds I-XIV on the activity of thymidine and deoxycytidine kinases and pyrimidine nucleoside phosphorylases, isolated and partially purified from tumor cells of animals and humans was also investigated. In some of the experiments, radioactive precursors /sup 14/C-dThd and /sup 3/H-dCyd or (/sup 3/H)deoxyuridine were injected. The kinetics of the competitive phosphorylation of /sup 14/C-dThd in the presence of antiherpetic nucleosides and the phosphorylation of these compounds with gamma-/sup 32/P-ATP as the second substrate of the reaction were studied.

Cyclic acetals of N-acyl derivatives of 3-formylindole and 3-formyl-5-phenyl-7-ethylthiopyrrolo[3,2-d]pyrimidine, which may be viewed as analogs of the α and β anomers of C-nucleosides modified in the carbohydrate part of the molecule, have been obtained.

2-Β-D-Ribofuranosyl-4-methylthio-5-methoxycarbonyl-1,2,3-triazole was obtained by fusing 4-methylthio-5-methoxycarbonyl-1,2,3-triazole together with tetraacyl-D-ribofuranose, followed by deacylation, and its amide and hydrazide were prepared. The structures of the new nucleosides were established by converting them into known 2-nucleosides of 1,2,3-triazol-4-yl-carboxylic acid derivatives.

A number of compounds with valuable biological properties have been found among the pyrazolo[3,4-d]pyrimidines and their nucleosides. Thus, experimental antitumor activity and/or antiparasitic properties have been exhibited by nucleosides of 4-aminopyrazolo[3,4-d]. pyrimidine, allopurinol (4-oxypyrazolo[3,4-d]pyrimidine) [6], and 4-methylmercaptopyrazolo' [3,4-d]pyrimidine [3]. Of particular interest are the nucleosides of pyrazolo[3,4-d]pyrimidines which have residues of functional carboxylic acids in position 3 of the hetero ring. As has been illustrated by nucleosides of 4-substituted and certain 4,6-bisubstituted pyrazolo[3,4-d]pyrimidines, the introuction of a nitrile, carbamoyl, thiocarbamoyl and similar groups to position 3 results in greater cytotoxic and antitumor activity [2, 7, i0, ii].

3-Cyano-4,6-bis(methylthio)pyrazolo[3,4-d]pyrimidine was synthesized by cyclization of 3,4-dicyano-5-aminopyrazole with CS2 in pyridine with subsequent Dimroth rearrangement and methylation of the resulting 3-cyano-4,6-dimercaptopyrazolo[3,4-d]-pyrimidine with methyl iodide. Glycosylation of the product by fusion with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose in the presence of iodine gave 1-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)-3-cyano-4,6-bis(methylthio)pyrazolo[3,4-d]pyrimidine, the deacetylation of which with a 1% solution of hydrogen chloride in methanol led to 3-cyano-4,6-bis(methylthio)pyrazolo[3,4-d]pyrimidine 1-fiboside. The structures of the compounds were established by IR, UV, circular dichroism, PMR, and 13NMR spectroscopy.

The N-alkylation of some substituted pyrazoles and pyrazolo[3,4-d]pyrimidines with dimethylformamide diethyl acetal or triethyl orthoformate has been examined. Dimethylformamide diethyl acetal is more effective as an alkylating agent than triethyl orthoformate. Alkylation of 3-methoxycarbonylpyrazole gives a mixture of N-1- and N-2-ethyl derivatives. Alkylation of pyrazolo[3,4-d]pyrimidines takes place at the 1-position of the pyrazole ring only. In the case of thio-derivatives of pyrazolo[3,4-d]pyrimidines, S-alkylation occurs in addition to N-alkylation.

In a study of the IR absorption spectra of diastereomeric (with respect to phosphorus) 2′,3′-O-alkylphosphonates of nucleosides it was shown that the IR spectra of the diastereomers differ at 820–860 (ΝO-P-O), 1040–1060 (ΝP-O-C), and 1250–1300 cm−1 (ΝP=O). Higher ΝO=P and ΝP-O-C values and lower ΝO-P-O values are observed for the R isomers (as compared with the S isomers), and this provides a possibility for the determination of the orientation of the P=O group relative to the protons of the phospholane ring in alkylphosphonates of nucleosides by comparison of the spectra of the diastereomers.

The N-alkylation of 4-chloro-5-cyano-1,2,3-triazole with methyl and ethyl orthoformate, and the dimethyl, diethyl and ethylene acetals of DMF has been examined. Methylation gives all three N-methyl isomers, whereas ethylation and hydroxyethylation gives the 2-N-alkyl derivatives only. It has been shown for the first time that it is possible to use DMF ethylene acetal to obtain N-hydroxyethylazoles. The structures of the products were established by13C NMR spectroscopy.

A number of new 1-aryloxy-5-methyl-1,2,3,6-tetrahydro-1,2,6-phosphadiazine-1,3-diones were obtained from arylphosphoric acid dichlorides through the corresponding diamidophosphoric acid esters. Conversion of the 1-phenoxy and 1-ethoxy derivatives to 6-methyl-4-hydroxypyrimidine under Vilsmeierformylation conditions was observed. These compounds were thionated to give the corresponding 1,3-dithiones; the 1-phenoxy derivative was subsequently methylated in the 6 position and animated to give the phosphorus-containing analog of 6-methyl-2-thiocytosine. The bromination of the 1-ethoxy compound and replacement of the bromine by a secondary amine residue were studied.

The condensation of 4-cyano-5-aminopyrazole or 3,4-dicyano-5-aminopyrazole with dimethylformamide diethylacetal was studied. It was shown that, in addition to the formation of dimethylaminomethyleneamino derivatives, alkylation of the pyrazole ring occurs under severe conditions without a solvent. Only the corresponding formamidino derivatives are formed when the same reactions are carried out in methanal under milder conditions. The site of addition of an ethyl group to the pyrazole ring in the N-alkyl derivatives obtained was established by 13C NMR and PMR spectroscopy. The possibility of the synthesis of 4-amino- or 4-methylmercaptopyrazolo[3,4-d]pyrimidines by cyclization of the corresponding dimethylamino- methyleneaminopyrazoles with a cyano group in the ortho position was demonstrated for the first time.

Methods for the preparation of aza and deaza analogs of purine nucleosides, viz., nucleosides of imidazo[4,5-d]-v-triazines, imidazo[4,5-b]pyridines, and imidazo[4,5-c]pyridines, and their properties are described. References to the synthesis of nucleosides of imidazo[4,5-d]pyridazines, imidazo[4,5-c]pyridazines, and imidazo[4,5-b]pyrazines are also given.

A number of 3,4,6-trisubstituted pyrazolo[3,4-d]pyrimidines and their 1-ribosides were synthesized from 3-cyano-4,6-dimethylmercaptopyrazolo [3,4-d]pyrimidine. The cyano group was converted to thiocarbamoyl, imido ester, carboxamidoximno, carboxamidrazono, carboxy, and amidino groups. The 4-methylmercapto group was replaced by mercapto, methoxy, amino, and hydrazino groups. The reactivities of methylmercapto and 3-cyano groups in substituted pyrazolo [3,4-d] pyrimidines and the corresponding nucleosides with respect to nucleophilic agents were compared. The introduction of a ribose residue in the 1 position facilitates nucleophilic addition to the 3-cyano group and replacement of the 4-methylmercapto group. High resistance of the 6-methylmercapto group to the action of nucleophilic agents and higher reactivity of the cyano groups as compared with methylmercapto groups were observed.

The condensation of 3,4-dicyano-5-aminopyrazole with ethyl orthoformate was studied. Under severe conditions (150 °C) the principal reaction product is N-ethyl-3,4-dicyano-5-ethoxymethylaminopyrazole. Alkylation of the pyrazole ring does not occur at 100 °C, but 3,4-dicyano-5-ethoxymethyleneaminopyrazole is formed. Isomeric 1- and 2-ethyl-4-aminopyrazolo[2,4-d]pyrimidine-3-carboxylic acid methyl imino esters were obtained by the action of a methanol solution of ammonia on the principal reaction product. This constitutes evidence that N-ethyl-3,4-dicyano-5-ethoxymethyleneaminopyrazole is a mixture of 1- and 2-ethyl-3,4-dicyano-5-ethoxymethyleneaminopyrazoles.

3-Cyanomethyl-4,6-dimethylmercaptopyrazolo[3,4-d]pyrimidine was synthesized on the basis of 3-cyanomethyl-4-cyano-5-aminopyrazole. Ribosylation of this product gave 1-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)-3-cyanomethyl-4,6-dimethylmercaptopyrazolo[3,4-d]pyrimidine in 63% yield and small amounts of the 1-α and 2-β isomers. A number of derivatives of 6-methylmercaptopyrazolo[3,4-d]pyrimidin-3-ylacetic acid and their 1-ribosides were synthesized. The 4-methylmercapto group was replaced by amino, hydrazino, oxo, N-piperidino, and N-morpholino groups. The nitrile group was saponified in an alkaline medium to carbamoyl and carboxy groups. The corresponding 4-morpholino and 4-piperidino derivatives were obtained by the reaction of 3-cyano-4,6-dimethylmercaptopyrazolo[3,4-d]pyrimidine per-O-acetylated 1-β-D-ribofuranoside with secondary cyclic amines. The high resistance of the 6-methylmercapto group to the action of nucleophilic agents and the higher reactivity of the 4-methylmercapto group as compared with the nitrile group are discussed. Data on the cytotoxic activity of the synthesized compounds were obtained.

It is shown on the basis of a study of the IR spectra of indazoles, pyrazolopyridines, and pyrazolopyrazine in the solid state and of their N-deutero-substituted derivatives and hydrochlorides at room temperature and at the temperature of liquid nitrogen that these heterocycles exist in a tautomeric form in which the labile hydrogen atom is localized on the nitrogen atom of the pyrazole ring. It was established that 6-aminopyrazolopyridine exists in the crystalline state in the amino form and that it is protonated at the ring nitrogen atom rather than at the amino group. The applicability of the temperature-shift method for the detection not only of γNH bands but also of γND bands is demonstrated.