Investigation of nitrogen- and sulfur-containing heterocycles. 39. Reactions of 2-mercapto-3-ureido- and 2-mercapto-3-aminopyridines with β-halo carbonyl compounds. Synthesis of 6-oxo derivatives of pyrido[2,3-b][1,5]thiazepines

The reaction of 2-mercapto-3-ureido- and 2-mercapto-3-aminopyridines with -halo derivatives of carbonyl compounds (ketones, acids, and aldehydes) and with acrylonitrile proceeds not only via the mercapto group but also via the amino group, as a result of which S--keto (carboxy, cyano) alkyl, N,S-bis(-ketoalkyl), and N,S-diacyl derivatives of pyridine are formed. The action of acids, alkalis, and dehydrating agents on 2-S--keto (carboxy, cyano) ethyl-3-aminoureidopyridines was studied. A method for the preparation of derivatives of a new heterocyclic system, viz., 6-oxopyrido [2,3-b] [1,5] thiazepine, by the reaction of 2-mercapto-3-aminopyridines with -bromopropionic acid and subsequent treatment of 2-(-car-boxyethyl) thio-8-aminopyridines with dicyclohexylcarbodiimide was developed.See [5] for Communication 38.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 634–639, May, 1981.     

Reaction of alkylsulfenyl chlorides with crotonic acid and its derivatives

Conclusions -Chloro--alkthiobutyric acid derivatives were obtained by the addition of methylsulfenyl chloride and-chloroethylsulfenyl chloride to crotonie acid and its derivatives, which isomerize quite rapidly to-alkthio--chlorobutyric acid derivatives. An exception are the acid chlorides of the-chloro--alkthio-butyric acids, which do not isomerize spontaneously.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2247–2249, October, 1972.     

Steroid compounds of marine sponges. VII. Preparation of derivatives of sokotrasterol and halistanol sulfates and structure-activity interrelationships among these compounds

Five new sulfated derivatives of sokotrasterol and halistanol have been obtained: 24-nor-5-cholane-2,3,6,23-tetraol 2,3,6-tri(sodium sulfate); 24-nor-5-cholane-2,3,6,23-tetraol 2,3,6-tri(sodium sulfate) 23-palmitate; 24,25-dimethyl-5-cholestane-2,3,6-triol 3-(sodium sulfate); 24,25-dimethyl-5-cholestane-2,3,6-triol 6-(sodium sulfate); and 24,25-dimethyl-5-cholestane-2,3,6-triol 2,6-di(sodium sulfate). The inhibiting and membranolytic properties of the polysulfated steroids from sponges and their derivatives have been studied. It has been shown that physiological activity in this series of compounds depends on biphilicity.Pacific Ocean Institute of Bioorganic Chemistry, Far Eastern Scientific Center, Academy of Sciences of the USSR, Vladivostok. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 441–445, July–August, 1986.     

Cardenolide glycosides ofCheiranthus allioni. XV. Glucocheiranthoside

Another new cardenolide glycoside has been isolated from the plantCheiranthus allioni Hort., and has been named glucocheiranthoside. Its chemical structure has been established as 3-(4-O--D-glucopyranosyl--D-gulmoethylpyranosyloxy)-14-hydroxy-19-oxo-5,14-card-20(22)-enolide.State Scientific Center for Drugs, Ukraine, 310085, Kharkov, USSR. ul. Astronomicheskaya, 33. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 269–271, March–April, 1994.     

Comparative study on inclusion complexations of antiinflammatory drug flurbiprofen with β-cyclodextrin and methylated β-cyclodextrins

Abstruct Some physicochemical properties of methylated -cyclodextrins, i.e., heptakis(2,6-di-O-methyl)--cyclodextrin (DM--CyD) and heptakis(2,3,6-tri-O-methyl)--cyclodextrin (TM--CyD) were compared with those of natural -cyclodextrin (-CyD). Inclusion behaviors of -CyD and methylated -CyDs in water and in solid state were studied by solubility analysis, spectroscopies (UV, CD,¹³C-NMR and IR), X-ray diffractometry and thermal analysis, using an antiinflammatory drug flurbiprofen (FP) as a guest molecule. The spectral data suggest that the inclusion mode of FP-TM--CyD is somewhat different from those of FP--CyD and FP-DM--CyD. The solid complexes of FP with - and methylated -CyDs were obtained in molar ratio of 11, and their dissolution behavior and release from suppository base were examined. The data are presented suggesting that DM--CyD is particularly useful for improving the pharmaceutical properties of FP in various dosage forms.     

Chlorolysis of β-functionalized alkyl polyfluoroalkenyl sulfides

Chlorolysis of -functionalized alkyl polyfluoroalkenyl sulfides giving rise to -functionalized polyfluoroalkenesulfenyl chlorides was examined. -Cyano-containing sulfenyl chlorides underwent intramolecular cyclization at the nitrile group to form substituted isothiazoles.     

Reaction of β-aroylacrylic acids with 1-substituted 3,4-dihydroisoquinolines

The reactions of -aroylacrylic acids and their methyl esters with 1-methyl- and 1-benzyl-3,4-dihydroisoquinolines lead to the formation of -substituted -aroylpropionic acids and their esters, which undergo cyclization to benzopyrrocolinone derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 943–945, July, 1979.     

Sulfur-containing carboxylic acids. Communication 3. Synthesis of β-(acetylthio)alkanoic acids amides

Conclusions Amides of -mercapto- or -(acetylthio)alkanoic acids were obtained by the reaction of -thiolactones or -(acetylthio)alkanoic acid chlorides with amines.For Communication 2, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 616–621, March, 1983.     

Triterpene glycosides ofClimacoptera transoxana. III. The structures of copterosides E and F

New triterpene glycosides have been isolated from the epigeal part ofClimacoptera transoxana (Iljin) Botsch. — copterosides E and F. According to chemical transformations and physicochemical characteristics, copteroside E has the structure of oleanolic acid 28-O--D-glucopyranoside 3-O-{[O--D-xylopyranosyl-(12)]-[O--D-xylopyranosyl-(14)]--D-glucuronopyranoside} and copteroside F that that of hederagenin 28-O--D-glucopyranoside 3-O-{[O--D-xylopyranosyl-(12)]-[O--D-xylopyranosyl-(14)]--D-glucopyranoside}.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 596–601, September–October, 1983.     

Withasteroids ofPhysalis. V. A study of the1H and13C NMR spectra of the withasteroids visconolide and 28-hydroxywithaperuvin C

The PMR and¹³C NMR spectra of new withasteroids — visconolide and 28-hydroxywithaperuvin C, isolated fromPhysalis viscosa L. — have been investigated. A detailed analysis of the spectral characteristics obtained is given. For visconolide is proposed the structure of 4,12,17,28-pentahydroxy-1-oxo-5, 6-epoxy-22R-witha-2,24-dienolide, and for 28-hydroxywithaperuvin C that of 6,14,17,20R, 28-pentahydroxy-l-oxo-22R-witha-2, 4, 24-trienolide.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 657–663, September–October, 1985.     

Synthesis of trichlorogermyl derivatives of β-furylpropionic acids

Conclusions Trichlorogermyl derivatives of -furylpropionic acids were obtained regiospecifically by the addition of HGeCl₃ to esters of -furylacrylic acids.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 3, pp. 717–719, March, 1986.     

Reaction of ammonia with β,β′-dithioalkyl-α,α′-divinyl ketones

Conclusions Syntheses are reported for ,-dithioalkyldivinyl ketones, which react with ammonia to give -amino--thioalkyldivinyl ketones.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2414–2415, October, 1988.The authors thank A. M. Kachurin for assistance in taking the spectra.     

The reaction of aryl(β-halogenoallyl)amines with orthophosphoric and polyphosphoric acids

The cyclization of secondary and tertiary aryl(-halogenoallyl)amines into 2-methylindoles on heating in orthophosphoric or polyphosphoric acid has been studied. Cyclization of N,N-di(-bromoallyl)-p-toluidines in polyphosphoric acid forms 1-(-bromoallyl)-2, 5-dimethyl-indole and 2, 5-dimethylindole. The probable mechanism of the rearrangement in the formation of the indole ring is put forward.     

Chemistry and Structure of Diterpene Compounds of the Kaurane Series: IV.1 Acylation of Reduction Products of the Isosteviol Keto Group

Acetylation with acetic anhydride of (4,8,13)-16-hydroxy-13-methyl-17-norkaurane-18-carboxylic acid and its methyl ester, obtained by reduction of isosteviol and (4,8,13)-18-methoxycarbonyl-13-methyl-16-oxo-17-norkaurane, respectively, gives rise to (4,8,13)-16-acetoxy-13-methyl-17-norkaurane-18-carboxylic acid and (4,8,13)-16-acetoxy-18-methoxycarbonyl-13-methyl-17-norkaurane. The molecular and crystal structures of the compounds were established by X-ray diffraction.     

Protolysis of some α-amino-β-(1-pyrimidyl)propionic acids and their analogs

The protolysis constants of -(1-uracilyl)propionitriles and -(1-uracilyl)propionic -amino--(1-pyrimidyl)propionic, and -amino--(1-pyrimidyl)butyric acids (willardiine analogs) were determined. The electronic effect of substituents and of transannular interaction of the groups on the deprotonation constants is discussed. -(1-Uracilyl)--alanine (willardiine) was isolated by Gmelin from the seeds of Acacia willardiana.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 708–712, May, 1972.     

Reaction of dimethylaminomethylenemalonaldehyde bis-N,O-acetal with ketones. A novel route to N-methylpyrroles

Condensation of the bis-N,O-acetal of amethylarrtinomethylenerrzalonaldehyde with ketones, -dimethylaminovinylketones, and -dimethylaminodienones is accompanied by an unusual intramolecular cyclization to give cross conjugated cyclic or acylic ketones containing an N-methyl pyrrole ring in the - or - and'-positions. This is a novel route to substituted pyrroles. Treatment of the bis-N,O-acetal of dimethylaminomethylenemalonaldehyde with 2-(3'-dimethylaminopropen-2'-ylidene)cyclopentanone gave a polyenyl tris-dimethylaminodiketone.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913. Translated from Khimiya Geterotsiklicheskikh Soednenii, No.5, pp. 654–662, May, 1996. Original article submitted February 14, 1996.     

Prolonged release of drug from triacetyl-β-CyD complex for oral and rectal administration

Triacetyl--cyclodextrin (TA--CyD), a hydrophobic cyclodextrin derivative, that is insoluble in water, was used to form a complex with flufenamic acid (FA). FA-TA--CyD complex formation was demonstrated by differential scanning calorimetry and powder X-ray diffractometry. The release rate of FA from the FA-TA--CyD complexes in phosphate buffer pH 6.8 was significantly retarded compared to that of FA from the FA and glucose mixture. When the FA-TA--CyD complexes were administered directly into the intraduodenal lumen, the plasma concentration of FA remained at a plateau level (10-18 g/ml) for 6–8 h. An increased mean residence time of FA following FA-TA--CyD complexes administration was observed. These results indicate that TA--CyD may serve as a hydrophobic carrier in prolonged-release preparations of FA.     

Synthesen von Heterocyclen, 75. Mitt.: Über 4-Hydroxy-pyridone

Zusammenfassung Primäre und sekundäre Enaminderivate, die aus -Ketoestern und -Diketonen darstellbar sind, reagieren mit Malonylchloriden bzw. Malonsäuren in Acetanhydrid zu 4-Hydroxypyridonen.

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Primary and secondary enamines readily obtained from -ketoesters and -diketones react with malonyl chlorides or malonic acids in acetic anhydride to yield derivatives of 4-hydroxy-2-pyridone.

     

Complex Formation Between Alkane-α,ω-Diols and Cyclodextrins Studied by Partial Molar Volume and Compressibility Measurements

The binding of a series of alkane-,-diols, HO(CH₂)_nOH, n = 4 to 7, to - and -cyclodextrin (CD) has been studied by measurements of partial molar volumes (PMVs) and isentropic partial molar compressibilities (PMCs) at 25°C. From the PMV and PMC data, changes in the partial molar quantities upon going from a free state in aqueous solution to a complexed state were evaluated for the diols. Negative changes in PMV and PMC were observed for complex formation with -CD, while positive values were obtained for the -CD complexes. Equilibrium constants for the different complexes, assuming the formation of 1:1 complexes, were evaluated from the PMV and/or PMC data, and were found to increase with increasing chain length of the included diol for both - and -CD complexes. The equilibrium constant for complex formation is generally higher for the -CD than for the -CD complexes.