Studies on steroids. CCLIII. Capillary gas chromatographic behaviour of diethylhydrogensilyl-diethylsilylene derivatives of stereoisomeric bile acids.

The capillary gas chromatographic behaviour of diethylhydrogensilyl (DEHS) ethers and/or diethylsilylene (DES) derivatives of fifty bile acids including 4- and 6-hydroxylated compounds is described. The methylene unit (MU) values of methyl and pentafluorobenzyl esters of bile acids were determined as their trimethylsilyl (TMS), dimethylethylsilyl (DMES) ethers and DEHS-DES derivatives. The differences in methylene unit values between the corresponding TMS ethers and DMES ethers or DEHS-DES derivatives were used for estimating the number and stereochemistry of hydroxyl groups on the steroid nucleus. On treatment with the silylating agent N,O-bis (diethylhydrogensilyl)trifluoroacetamide, bile acids possessing isolated hydroxyl in addition to diaxial trans-glycol groups were easily converted into the DEHS ehters, whereas those having a vicinal glycol group except for the diaxial group were converted into cyclic DES derivatives. The mass spectrometric properties obtained with negative-ion chemical ionization detection are discussed.     

On triazoles. XXIX. The reaction of triazolyl thiohydrazides with isocyanates and isothiocyanates

Different N-methylsubstituted, N'-methylsubstituted and N,N'-unsubstituted triazol-1-ylcarbothiohydrazides were reacted with isocyanates and isothiocyanates to yield the corresponding carbamoyl and thiocarbamoyl derivatives 4 . The thiocarbamoyl derivatives could be cyclised by heating in dimethylformamide or 10% sodium hydroxide solution, reacting them with dicyclohexylcarbodiimide or thier alkylation to the corresponding 1,3,4-thiadiazoles 12 and 16 , and derivatives 5 formed by splitting the triazole moiety. Cleaved derivatives 9 and 11 were also formed in the reaction of thiocarbamoyl derivatives 4 with carbon disulfide in the absence or presence of methyl iodide, respectively. Spectroscopic evidence is given for the structure of products obtained.     

Stilbene Derivatives from Gnetum montanum Markgr. f. megalocarpum Markgr.

Three new stilbene derivatives, gnetumelin A ( 1 ), gnetumelin B ( 2 ), and gnetumelin C ( 3 ), along with the nine known stilbene derivatives 4 – 12 were isolated from Gnetum montanum Markgr . f. megalocarpum Markgr. Their structures were determined by spectroscopic analysis and comparison of the data with reported ones.     

Heterocyclic compounds. VII. Synthesis of thiadiazasteroid analogs

The synthesis of a number of β-northiadiaza steroid analogs has been described. Suitable o-aminonitriles were acylated with γ-chlorobutyryl chloride. These amidonitriles were cyclized to substituted γ-lactams and subsequently to the tetracyclic products. To functionalize the “17-position” in these steroids, the intermediate γ-lactams were converted to arylidene derivatives before cyclization to the tetracyclic derivatives.     

Diethylhydrogensilyl-cyclic diethylsilylene derivatives in gas chromatography-mass spectrometry of prostanoids. III. F alpha-prostaglandins and thromboxane B2 derivatives

The gas chromatographic (GC) and GC-mass spectrometric properties of the diethylhydrogensilyl-cyclic diethylsilylene (DEHS-DES) derivatives of prostaglandin (PG) F1 alpha methyl ester, PGF2 alpha methyl ester, 6-keto-PGF1 alpha methyl ester-alkyloxime and thromboxane (TX) B2 methyl ester-alkyloxime and the DES derivative of 13,14-dihydro-15-keto-PGF2 alpha methyl ester-alkyloxime were studied. When the ketonic PGs and TXB2 were converted into their methyloxime derivatives, the methylene unit values of these five prostanoid derivatives were slightly greater than those of the corresponding dimethylethylsilyl ether derivatives. When the ketonic PGs were converted into their corresponding ethyloxime derivatives, baseline separation was achieved in 20 min by use of a methylsilicone cross-linked fused-silica capillary column. The mass spectra of these derivatives were characterized by the ion at m/z 157 for F alpha prostaglandins and m/z 269 for TXB2. The major fragmentations were directed by the DES group, and other fragmentations common to the prostanoid derivatives were losses of an ethyl radical at the silicon atom, C5H11 hydrocarbon fragment, diethylhydrogensilanol and C15-C20 hydrocarbon fragment. The mass fragmentations of these prostanoid derivatives are briefly discussed. GC with high-resolution selected-ion monitoring was carried out for the TXB2 derivative at a resolution of 8000 by monitoring the ion at m/z 269.1573. A 25-pg amount of this derivative showed a well shaped doublet with a signal-to-noise ratio of more than 300:1.     

Mass spectral investigations on trichothecene mycotoxins. III. Synthesis, characterization and applications of pentafluoropropionyl and trifluoroacetyl esters of simple trichothecenes

The pentafluoropropionyl, (PFP) and trifluoroacetyl (TFA) esters of several naturally occurring and synthetically modified simple trichothecenes were synthesized in nanogram amounts and characterized. Optimum conditions for the gas chromatographic (GC) separation of these derivatives and their analysis by negative ion chemical ionization (NICI) mass spectrometric technique were determined. These perfluoroacyl derivatives under the NICI conditions undergo limited but characteristic fragmentations similar to the fragmentations of heptafluorobutyryl esters of trichothecenes under the same conditions. Characteristic ions for the specific detection and accurate quantification of these PFP and TFA derivatives were chosen. Preliminary results indicated that the PFP derivatives are better suited for the analysis of simple trichothecenes by GC-NICI-MS technique. Ultra trace (0.5-2.0 pg) amounts of these PFP derivatives were detected by the developed procedure.     

Synthesis and platelet aggregation inhibitory activity of diphenylazole derivatives. I. Thiazole and imidazole derivatives

Diphenylimidazole and diphenylthiazole derivatives were synthesized and tested as inhibitors of platelet aggregation in in vitro experiments with the rabbit. Diphenylthiazole derivatives (10) were more potent than diphenylimidazole derivatives (4) in inhibiting arachidonic acid-induced platelet aggregation of rabbit platelet-rich plasma. Two diphenylimidazole and eight diphenylthiazole derivatives were evaluated for ex vivo arachidonic acid and collagen-induced platelet aggregation inhibitory activity using guinea pigs. In these compounds, 4,5-bis(4-methoxyphenyl)-2-(1,5-dimethyl-2-pyrrolyl)thiazole (10n) showed strong activity in vitro and ex vivo. The ex vivo activity of 10n was 200 times stronger than that of aspirin. The mechanism of the activity of 10n was the inhibition of cyclo-oxygenase.     

Modified Coumarins. 16. Cyclohexane-Annelated Analogs of Pyranocoumarins

Modified derivatives of angular and linear pyranocoumarins containing a condensed cyclohexane moiety were prepared by fusing a 2,2-dimethyltetrahydropyran ring to the coumarin system and annelating a pyrone ring to derivatives of 2,2-dimethylchromane. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 313–318, July–August, 2005.     

Functional derivatives of sterically hindered amines. 1. Glycidyl compounds

Four polymerizable glycidyl derivatives of sterically hindered amines were prepared from derivatives of 2, 2, 6, 6-tetramethyl-4-hydroxypiperidine and 14, 16-dioxo-7, 15-diazadispiro [5, 1, 5, 3] hexadecane. One of them is a stable nitroxyl derivative.     

Chemical modification of fumagillin. II. 6-Amino-6-deoxyfumagillol and its derivatives.

6-Amino-6-deoxyfumagillol (5) was synthesized by reductive amination of 6-oxo-6-deoxyfumagillol (4), which was obtained by oxidation of fumagillol (2). The reduction proceeded stereoselectively by the equatorial attack of hydride and 5 was found to have the same stereochemistry as that of 2. Several derivatives of 5 were prepared and most of them showed anti-angiogenic activity comparable to that of fumagillol derivatives.     

Die Glykoside der Wurzeln von Glossostelma carsoni (N. E. BR.) BULLOCK. Glykoside und Aglykone, 297. Mitteilung

Pentacyclic triterpenes, sterols, cardenolides and pregnane derivatives could be identified in extracts from roots of Glossostelma carsoni (N.E. BR .) Bullock. From the first group, the following substances could be isolated in crystalline form: β-amyrin, lupeol, their 3-O-acetyl derivatives, and 3-O-isovaleryl-β-amyrin. The sterols were isolated in the form of two mixed but crystalline fractions. The less polar fraction was shown to be a mixture of β-sitosterol, campesterol, stigmasterol, and cholesterol (stereoisomers are not excluded); the more polar fraction is probably a mixture of monohydroxy derivatives of the four above mentioned sterols.     

On triazoles. XII. The carbamoylation and thiocarbamoylation of 5-amino-1,2,4-triazoles

The reaction of 5-amino-3-R-1H-1,2,4-triazoles 1 with isocyanates 2 (X = O) and isothiocyanates 2 (X = S) was studied. It was stated that with isocyanates 3a (X = O) type ring-carbamoylated products were formed which did not rearrange to the corresponding exo-carbamoylated derivatives 6a (X = O). On the other hand the thiocarbamoylation of derivatives 1 provided at mild conditions lead to derivatives 3a (X = S) which could be rearranged by heating to derivatives 6a (X = S). In one case the isomeric 4a (X = S) type derivative was also isolated. The comparison of the ir, uv, pmr and cmr spectra of the isomers isolated with the corresponding spectra of the carbamoylated and thiocarbamoylated 3,5-diamino-1,2,4-triazole derivatives helped to prove unequivocally the isomeric and tautomeric structure of compounds obtained giving a possibility to correct many confusions in the literature.     

New synthesis of condensed hydropyridazine derivatives. VI

The reactivity of some indole derivatives towards the semicarbazone of ω-bromoacetophenone has been reported. Substituents at position 1 and 2 of the indole ring greatly affect the course of the reaction. 1,4,4a,9a-Tetrahydro-9H-pyridazino[3,4-b]indole derivatives or 3-indolyl derivatives were obtained depending on the substituents. The structures were assigned on the basis of satisfactory analytical and spectroscopic data.     

Neuraminic acid and related compounds. V. Syntheses of biologically active sialosyl-glycerol derivatives and galactosyl-glycerol derivative

New 1-acyl-sialosyl-glycerol derivatives (1a--d alpha, 1a--d beta, 2 alpha, 2 beta, which mimic the structure of the capsular polysaccharide of group C meningococcal were synthesized by the use of a chiral glycerol derivative, and were found to have phospholipases A2 and C inhibitory activities. Furthermore, synthesis of 2-palmitoyl-sialosyl-glycerol derivative (4 alpha, 4 beta, 5 alpha, 5 beta), galactosyl-glycerol derivative (6), and sialosyl-galactosyl-glycerol derivative (7) were carried out to examine the difference between these activities. Among these sialosyl derivatives, 3-palmitoyl-sialosyl-glycerol derivatives (1--3 alpha, 1--3 beta) demonstrated the most potent inhibitory activities.     

Mannich and eschweiler-clarke reaction of 1-benzyl-1,2,3,4-tetrahydroisoquinolines. Studies on the syntheses of heterocyclic compounds. Part CCCXVIII

Modified Mannich reactions of a number of 1-benzyl-1,2,3,4-tetrahydroisoquinolines (Ia-Ie) were attempted to afford the corresponding protoberberine derivatives (IIa-IIe) in good yield. Treatment of both If and Ig with formalin under a variety of Mannich or Eschweiler-Clarke conditions did not give the expected protoberberine derivatives IIf and IIg, but afforded the N-methyl derivatives (VIIa) and (VIIb), respectively.     

Polycondensed nitrogen heterocycles. Part 17. Isoxazolo[4,3-d]pyrazolo[3,4-f][1,2,3]triazepine. A new ring system

The title compounds were prepared by nitration of compounds 2 , reduction of the dinitro derivatives 4 and diazotization of the diamino derivatives 6 followed by an intramolecular coupling reaction. Compound 4a showed good activity against Salmonella cholerasuis and Clostridium perfringens bacteria.     

The preparation and reactions of polymeric azides. I. The reaction of poly(vinylbenzyl azide) with acetylenic and olefinic derivatives

The preparation and reactions of polymers and copolymers of vinylbenzyl azide with olefinic and acetylenic derivatives are described. With acetylenes, a 1,3-dipolar addition gave almost complete conversion to polymeric 1,2,3-triazoles. Yields were excellent and light-colored derivatives were obtained.     

Saturated heterocycles. Part 209. Synthesis of 1-cyclohexyl-substituted isoquinoline derivatives

In contrast with earlier literature data [7], both acrylic esters and acrylonitrile underwent Michael addition to l-methyl-3,4-dihydroisoquinolines 1-4 to yield the diesters 5-9 or the dinitrile 10 , respectively. Compounds 5-10 were converted by Claisen condensation to 1-[(3′-methoxycarbonyl- or 1-[(3′-ethoxycarbonyl-4′-oxo)-l'-cyclohexyl]-3,4-dihydroisoquinoline derivatives 11-16 . Several derivatives of 12 were prepared. The new compounds possess various pharmacological actions.     

Studies on the syntheses of heterocyclic compounds. Part CCCXXIX. Syntheses of i-spiroisoquinoline derivatives by phenolic cyclization

Phenolic cyclization of 2-(3-hydroxyphenyl)-2-methylethylamine (XIIIa) and 2-(3-hydroxyphenyl)phenethylamine (XIIIb) with various carbonyl compounds afforded eight types of corresponding 1-spirocycloalkano- and 1-spiroheterocycloalkano-1,2,3,4-tetrahydroisoquinoline derivatives (1-VIII) and 1,1-disubstituted-1, 2,3,4-tetrahydroisoquinoline derivative (IX). The acetyl derivatives of VI and IX and the benzoyl derivatives of III and V were also prepared. In addition, a synthetic method for obtaining the starting phenethylamines was examined.     

Benzocycloheptapyridines. Analogs of azatadine

Certain 3-substituted derivatives of cyproheptadine ( 1a ) have been shown to possess potent pharmacological properties. The structural analogy between cyproheptadine and azatadine ( 2 ) prompted the preparation of 9-substituted derivatives of 2 and its 5,6-dehydro analog for pharmacological comparison. The 9-cyano and 9-trifluoromethylthio derivatives were prepared by direct displacement of the corresponding 9-bromo compounds. Acid hydrolysis of the nitriles generated the carboxylic acids. Oxidation of the trifluoromethylthio compounds 15a and 18a gave the epoxy sulfones 19a and 19b , which could not be deoxygenated. Therefore, the trifluoromethylsulfonyl moiety was introduced prior to the formation of the exocyclic olefin.