Potentially useful 17-, and 22÷25-membered macrolides containing azine or hydrazide groups were synthesized from tetrahydropyran via [1+1]-condensation at room temperature of 7-oxooctyl-7-oxooctanoate, which was obtained via Tishchenko reaction from 7-oxooctanal, with hydrazine hydrate and hydrazides of several dicarboxylic acids.Polyfunctional macroheterocycles with interesting complexing properties and biological activity are widely used as interphase-transfer catalysts, extractants, analytical reagents, and materials for creating ion-selective electrodes [1-3].Herein we report the synthesis of 17-(9), 22-(10), 23- (11), 24- (12), and 25-membered (13) macrolides that may exhibit complexing properties and biological activity and contain azine or hydrazide functional groups. The synthetic scheme is based on chemo-and regioselective transformations of a ketoalcohol (2) that is accessible in three steps from tetrahydropyran (1) [4]. Corey oxidation of 2 produced ketoaldehyde 3, which has been used to synthesize 9-oxo-2E-decenoic acid (multifunctional pheromone of honeybee Apis mellifera L.) [5], and small quantities (up to 15%) of 7-oxooctyl-7-oxooctanoate (4) by disproportionation of 3 via a Tishchenko reaction. The yield of 4 could be increased (up to 70%) by using the classical method [6] with catalytic quantities of aluminium triisopropoxide.[1+1]-Condensation of 4 in dioxane at high dilution and room temperature with hydrazine hydrate or dihydrazides of malonic (5), succinic (6), glutaric (7), and adipic (8) acids and subsequent successive work up of the reaction mixture with CH 2 Cl 2 and hexane (1:10 ratio) produced in good yields (40-50%) macrolides with azine (9) or hydrazide (10-13) groups, respectively.

Eight potentially useful 15-, 17-, 20-, and 22-25-membered macrolides having an azine or hydrazide fragment were synthesized starting from L-menthol, tetrahydropyran, and 4-methyltetrahydropyran via [1 + 1]-condensation of hydrazine hydrate and some dicarboxylic dihydrazides with 7-oxooctyl 7-oxooctanoate, 3-methyl-7-oxooctyl 3-methyl-7-oxooctanoate, and (3R)-3,7-dimethyl-6-oxooctyl (3R)-3,7-dimethyl-6-oxooctanoate obtained by the Tishchenko reaction from 7-oxo-, 3-methyl-7-oxo, and (3R)-3,7-dimethyl-6-oxooctanals, respectively. * For preliminary communications, see [1,2].It is known [3-6] that functionalized macrocyclic compounds are widely used in organic and petrochemical synthesis, detection and separation of metals by extraction, sorption and chromatographic analytical methods, ionometry, design of cardio-and psychotropic agents and studies on mechanisms of their action, development of antimicrobial, antiparasitic, and antitumor drugs, etc.In the present article we describe efficient ways of synthesis of 15-, 17-, 20-, and 22-25-membered macrolides having an azine or hydrazide fragment starting from accessible synthetic [tetrahydropyran (I) and 4-methyltetrahydropyran (II)] and natural [L-menthol (III)] compounds. The proposed approach is based on initial transformation of cyclic substrate into the corresponding oxo aldehydes, 7-oxo-, 3-methyl-7-oxo-, and (3R)-3,7-dimethyl-6-oxooctanals IV-VI, according to the procedure reported in [1,2], and their subsequent Tishchenko disproportionation to give dioxo esters VII-IX.[1+1]-Condensation of the latter with hydrazine hydrate or malonic, succinic, glutaric, and adipic acid dihydrazides in strongly dilute dioxane solution at room temperature, followed by treatment of the reaction mixture with methylene chloride-hexane (1 : 10), afforded 40-54% of macrolides having a ketone azine (X, XI) or bis-hydrazide fragment (XII-XVII), respectively (Schemes 1, 2).The structure of macrocyclic compounds X-XVII was determined by IR spectroscopy and 1 H and 13 C NMR; according to the HPLC data, their purity was ~95%. The NMR spectra of X-XVII were analyzed by comparing with the spectra of initial compounds, dioxo esters VII-IX and dicarboxylic acid dihydrazides. The 13 C NMR spectra of compounds XI and XVII lacked signals of carbonyl carbon atoms (δ C 214.13 and 214.42 ppm) and methylene and methine groups in the α-position to the carbonyl group (δ C 35.08, 37.53 ppm), which were typical of initial dioxo ester IX. In addition, no hydrazide NH 2 signal was observed in the 1 H NMR spectrum of macrocycle XVII (δ 4.75 ppm in the spectrum of the initial hydrazide). These findings indicate that the products have cyclic structure rather than the structure of acyclic substitution products. The 13 C NMR spectrum of XI, apart from the singlet at δ C 170.64 ppm (ester carbonyl carbon atom), contained a singlet at δ C 169.24 ppm due to C=N carbon atoms, which is consistent with the formation of macrocycle possessing an azine fragment.Compound XVII displayed in the 13 C NMR spectrum a signal ...

The gasification processes of coal, coal-water slurry, and natural bitumen were studied. A new method involving application of hydrocarbon fuels was proposed. It allows one to create process schemes which can be adopted for changing feedstock's properties in a wide range by the variation of gasification parameters. The integrated gasification unit allows using the local resources and not being dependent on external fuel deliveries. However, for designing such projects, it is necessary to study the physicochemical processes involved in the thermochemical processing of various fuel types. For calculation of gas composition, three fuel types were selected: Kamsky long-flame coal, coal-water slurry based at Kama coal dust, and natural bitumen from Ashalchy oil field. During thermochemical processing of various feedstock types, by varying gasification parameters, syngas with the required application ratio of CO/H 2 was obtained. These fuels have various compositions, but they are located at one region. The syngas thus produced may be used in the chemical and energy industries.

Efficient procedures for the synthesis of 21-24-and 28-31-membered macrocyclic azino diesters and dihydrazido diesters were developed starting from L-menthol, Δ 3 -carene, (+)-α-pinene, tetrahydropyran, and 4-methyltetrahydropyran. The key steps in these syntheses were consecutive [2 + 1]-and [1 + 1]-condensations. The 31-membered dihydrazido diester exhibited strong antibacterial activity.* For preliminary communications, see [1][2][3][4].We recently reported [5] on the synthesis of eight potentially useful 15-, 17-, 20-, and 22-25-membered macrocycles having an azine or hydrazide fragment starting from L-menthol (I), tetrahydropyran (II), and 4-methyltetrahydropyran (III) via consecutive Tishchenko reaction and [1 + 1]-condensation.We now propose efficient procedures for the transformation of compounds I-III, as well as of accessible monoterpenes, Δ 3 -carene (IV) and (+)-α-pinene (V), into macrocyclic azino diesters XXI-XXIX and dihydrazido diesters XXX-XXXIX. All these procedures are based on initial transformation of compounds I-V into the corresponding hydroxy ketones: (6R)-8-hydroxy-2,6-dimethyloctan-3-one (VI). The subsequent [2 + 1]-condensation of compounds VI-X with glutaric and adipic acid dichlorides afforded open-chain diesters XI-XX containing two fragments of ketones VI-X as alcohol residues. Dioxo diesters XI-XX were then subjected to cyclization via [1 + 1]-condensation with hydrazine hydrate and glutaric acid dihydrazide in strongly dilute dioxane solution at room temperature to obtain azino diesters XXI-XXIX and dihydrazido diesters XXX-XXXIX, respectively (Schemes 1-4). The purity of intermediate compounds XI-XX and target macroheterocycles XXI-XXXIX was checked by HPLC, and their structure was confirmed by IR, 1 H and 13 C NMR, and mass spectra.The synthesized compounds were tested for biological activity at the Noncontagious Internal Diseases, Clinical Diagnostics, and Pharmacology Department, Bashkir State Agrarian University [4]; it was found that 31-membered macrocyclic dihydrazido diester XXXIII showed in vitro and in vivo antibacterial activity comparable with the activity of Erythromycin. EXPERIMENTALThe IR spectra were recorded on a UR-20 spectrometer from thin films. The NMR spectra were measured on a Bruker AM-300 spectrometer at 300.13 MHz for 1 H and 75.47 MHz for 13 C using CDCl 3 as solvent and tetramethylsilane as internal reference. Chromatographic analysis was performed on Chrom-5 [1.2-m column, stationary phase 5% of SE-30 on Chromaton N-AW-DMCS (0.16-0.20 mm), oven temperature 50-300°C] and Chrom-41 instruments [2.4-m column, stationary phase PEG-6000, oven temperature 50-200°C]; carrier gas helium. HPLC analyses were obtained on a Shimadzu LC-20AD liquid chromatograph equipped with an SPD M20A diode matrix detector [250 × 4.6-mm Phenomenex column; sorbent Luna C18, grain size 5 μm; eluent water-acetonitrile, flow rate 1 ml/min; analytical wavelength 215 nm]. Silica gel, 70-230 μm

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Most macrocycles have unusual properties and broad applications [1]. Therefore, methods for preparing such compounds with various functional groups must be devised in order to develop their chemistry, modern pharmacology, and advanced technology.Herein we report the synthesis of potentially biologically and pharmacologically active 30-(9, 11) and 31-membered (10, 12) symmetric macrocycles containing two esters and two hydrazides. Tetrahydropyran (1) and 4-methyltetrahydropyran (2) were converted in three steps [2, 3] to hydroxyketones 3 and 4, [2+1]-condensation of which with glutaric and adipic chlorides gave bis-derivatives 5-8 in which the two ketone C atoms of 3 or 4 were linked by diester spacers. Ring closure of key diketodiesters 5-8 into the desired macrocycles 9-12 was carried out via [1+1]-condensation with glutaric dihydrazide in dioxane at room temperature under high-dilution conditions.