Polyfluorinated arylnitrosamines

N-Methyl-, N-n-butyl-, N-t-butylperfluoroarylamines undergo nitrosation with nitrous acid to give the corresponding N-nitroso derivatives. Perfluoroaryl groups were selected from the benzene, indane, biphenyl, naphthalene and pyridine series. According to ¹H and ¹⁹F NMR spectra, N-nitroso-N-methyl derivatives of polyfluoroarenes consist of E and Z isomers with the former prevailing. The more bulky n-butyl group promotes an increase in the formation of Z isomers. Only Z isomers have been obtained from N-t-butyl derivatives of perfluorinated 4-toluidine and 4-aminopyridine. The structure of the Z isomer of N-nitroso-N-methylperfluoro-4-toluidine is confirmed by X-ray data.     

Cytotoxic cembranoids from the Red Sea soft coral, Sarcophyton auritum

Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of two new diterpene cembranoids; 2-epi-sarcophine (2) and (1R,2E,4S,6E,8R,11R,12R)-2,6-cembradiene-4,8,11,12-tetrol (4), as well as two known diterpene cembranoids, reported for the first time from this species, namely sarcophine (1) and (+)-7α,8β-dihydroxydeepoxysarcophine (3). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The isolated cembranoids were found to display high cytotoxicity against HepG2 (liver cancer cell line) and MCF-7 (breast cancer cell line).     

Stereoselective synthesis of protected (2S,3S)-N-methyl-5-hydroxyisoleucine, a component of halipeptins

The stereocontrolled synthesis of the protected (2S,3S)-N-methyl-5-hydroxyisoleucine, a component of halipeptins A and B with potent anti-inflammatory activity, has been achieved. The key steps include (i) installation of a double bond to bicyclic lactam 4 using N-tert-butyl phenylsulfinimidoyl chloride, (ii) highly exo-selective Michael reaction with lithium dimethylcuprate in the presence of chlorotrimethylsilane, and (iii) Ru-catalyzed oxidative deprotection of N,O-benzylidene acetal to the acid anhydride.     

Selective N-debenzylation of amides with p-TsOH

N-Benzylamides were debenzylated efficiently with 4 equiv. of p-TsOH in refluxing toluene. Good to quantitative yields of the desired primary amides were obtained within 2-4 h from a wide variety of N-2,4-dimethoxybenzylamides. N-4-Methoxylbenzyl amides and N-benzylamides were also debenzylated cleanly. In the case of N-2,4-dimethoxylbenzylamides, selective N-debenzylation was possible in the presence of N-Fmoc, N-t-BOC or N-trityl-protection. Protected amino acid amides survived these conditions without any detectable epimerization.     

Overlapping chemical and genetic diversity in Ligularia lamarum and Ligularia subspicata. Isolation of ten new eremophilanes and a new seco-bakkane compound

Root chemicals and DNA sequences were analyzed for Ligularialamarum samples collected in Yunnan and Sichuan Provinces of China and the relationship between the plant and Ligulariasubspicata, its taxonomically closest species, was examined. Both species produce furanoeremophilanes and eremophilan-8-one derivatives as the major components. Eleven new compounds, including a new seco-bakkane compound, were isolated. The two species were found to harbor overlapping intra-specific diversities with respect to the chemicals and the DNA sequences.     

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of common cutworm (Spodoptera litura)

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of Spodoptera litura was carried out. Substrate was converted to three new terpenoids, (+)-(1R,2S)-10-hydroxyfenchol, (+)-(1R,2R,3S)-8-hydroxyfenchol and (−)-(1S,2S,6S)-6-exo-hydroxyfenchol, and one known terpenoid, (−)-(1R,2R,3R)-9-hydroxyfenchol. These structures were established by NMR, IR, specific rotation and mass spectral studies.     

Selective immobilization of Acinetobacter junii on the natural zeolitized tuff in municipal wastewater

The immobilization of desired bacteria onto material was usually performed in synthetic media. The aim of this study was to test the immobilization of phosphate (P)-accumulating bacteria Acinetobacter junii onto natural zeolitized tuff (NZ) in the raw or sterilized municipal wastewater containing the common bacteria Escherichia coli and Enterococcus faecalis and the performance of immobilized A. junii in the same type of wastewater. In the sterilized wastewater which contained the mixture of A. junii, E. coli and E. faecalis, the A. junii was selectively immobilized onto NZ in significantly higher numbers than E. coli and E. faecalis. The A. junii added in the form of bioparticles to the wastewater containing E. coli and E. faecalis, multiplied and removed P from wastewater. The P removal from wastewater was a function of biomass of P-accumulating bacteria and not the amount of NZ or bioparticles used. The performance of A. junii was significantly better in membrane filtered than in autoclaved wastewater. The experiments that were performed in raw non sterilized wastewater showed that A. junii can be successfully immobilized onto NZ in competition with natively present heterotrophic bacteria, retain its metabolic activity and successfully remove P from such water, which makes this technology feasible from biotechnological aspect.     

Application of N,3-diaryl-3-oxo-propanethioamide in synthesis: an efficient and mild domino approach to highly substituted fused chromenones

A convenient and rapid synthesis of hitherto unknown 3-aroyl-4-aryl-2-phenylamino-4H-benzo[g]chromene-5,10-diones in high yield from β-aroyl-thioacetanilide, aromatic aldehyde, and 2-hydroxy-1,4-naphthoquinone via InCl₃ catalyzed one-pot three-component tandem Knoevenagel condensation–Michael addition–intramolecular cyclization–elimination reaction sequence is disclosed for the first time. This domino protocol has been used to obtain highly substituted pyrano[3,2-c]chromen-5(4H)-ones and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-ones from N,3-diaryl-3-oxo-propanethioamide, aromatic aldehyde, and 4-hydroxycoumarine or dimedone under mild reaction conditions. A plausible reaction mechanism is proposed. The 4H-pyrano[3,2-c]chromen-5-one and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one derivatives possessing 3-(2-chlorobenzoyl)-2-phenylamino-substituents further cyclized under basic conditions to yield penta-cyclic 7,13-diaryl-5,14-dioxa-13-aza-benzo[a]naphthacen-6,8(7H,13H)-dione and tetra-cyclic 6,12-diaryl-3,3-dimethyl-3,4-dihydro-2H-chromeno[2,3-b]quinolin-1,11(6H,12H)-dione, respectively.     

Interaction of 3,5-di-tert-butyl-o-benzoquinone with secondary amines—a pathway to new sterically hindered N,N-disubstituted o-aminophenols

The interaction of 3,5-di-tert-butyl-o-benzoquinone with secondary amines has been studied. The synthetic procedure was developed in order to synthesize a series of new N,N-disubstituted o-aminophenols. The interaction of 3,5-di-tert-butyl-o-benzoquinone with dimethylamine leads to 2-(N,N-dimethylamino)-4,6-di-tert-butyl-phenol, which is oxidized in the reaction medium by the parent 3,5-di-tert-butyl-o-benzoquinone forming spirocompound 4,5′,6,7′-tetra-tert-butyl-3′-methyl-3′H-spiro[1,3-benzodioxol-2,2′-[1,3]benzoxazole].     

N-(Diethoxyphosphoryl)-O-benzylhydroxylamine—a convenient substrate for the synthesis of N-substituted O-benzylhydroxylamines

Easily available N-(diethoxyphosphoryl)-O-benzylhydroxylamine was shown to be convenient, orthogonally protected substrate for regioselective N-alkylation by means of diverse halides under basic conditions (sodium hydride/tetrabutylammonium bromide). An efficient procedure for dephosphorylation of N-substituted N-(diethoxyphosphoryl)-O-benzylhydroxylamine to provide N-substituted O-benzylhydroxylamines was also established.     

Galanthamine analogs: 6H-benzofuro[3a,3,2,-e,f][1]benzazepine and 6H-benzofuro[3a,3,2-e,f][3]benzazepine

The known cholinesterase inhibitory capability of the Amarylidaceae alkaloid galanthamine prompted preparation of analogs in which the position of the nitrogen within the azepine ring is altered. The analogs 6H-benzofuro[3a,3,2-e,f][1]benzazepine and 6H-benzofuro[3a,3,2-e,f][3]benzazepine were prepared in 19 and 2.5%, respectively, following Kametani and Shimizu approaches, respectively. The aniline derivative 6H-benzofuro[3a,3,2-e,f][1]benzazepine failed to undergo most of the reactions typical for galanthamine. Thus, it neither oxidized to the analogous narwedine, nor epimerized to the analogous epigalanthamine, nor reduced to the lycoramine analog, under the conditions used for galanthamine.     

Selective O-acylation of unprotected N-benzylserine methyl ester and O,N-acyl transfer in the formation of cyclo[Asp-Ser] diketopiperazines

The synthesis of two diastereomeric cyclo[Asp-N-Bn-Ser] diketopiperazines (2a and 2b) was investigated. Initial formation of the Boc-aspartyl-N-benzyl serine isopeptide methyl esters (4a and 4b) was observed, which derive from the selective O-acylation of unprotected (S)- or (R)-N-benzylserine. This unexpected O-acylation is preferred over the formation of the tertiary amide and the resulting ester bond is stable in solution to O,N-acyl transfer. The O,N-acyl migration is then triggered by cleavage of the Boc protecting group and treatment with base, which also promotes immediate cyclization to the diketopiperazines.     

Three practical approaches for the synthesis of novel 4,7-dihetarylpyrazolo[1,5-a][1,3,5]triazines

Novel 4,7-dihetarylpyrazolo[1,5-a][1,3,5]triazines were synthesized from three different approaches. The first one, involved a one-step reaction between 5-amino-3-hetaryl-1H-pyrazoles and O,S-diethyl hetaroylimidothiocarbonates or S,S-diethyl hetaroylimidodithiocarbonates under solvent-free conditions employing microwave irradiation as the energy source. In the second approach, conventional heating under reflux in DMF as solvent was used instead of the microwave irradiation; and the third one was achieved from a two-step sequence through the treatment of 5-amino-3-hetaryl-1H-pyrazoles with hetaroyl isothiocyanates and the subsequent S-alkylation and cyclization process in DMF as solvent. Some intermediates were isolated and characterized to support the regiochemistry of the studied reactions. The structures of the new compounds were unambiguously established by spectroscopic and analytical techniques.     

Stereoselective radical cyclizations of N-(2-halobenzoyl)-cyclic ketene-N,X(X=O, S)-acetals

2-Alkyloxazolines and 2-alkylthiazolines react with 2-halobenzoyl chlorides to form N-(2-halobenzoyl)-cyclic ketene-N,O-acetals and N-(2-halobenzoyl)-cyclic ketene-N,S-acetals in excellent yields, respectively. These ketene acetals readily undergo stereocontrolled aryl radical cyclizations to afford the central six-membered rings of substituted-2,3,10,10α-tetrahydrooxazolo[3,2-b]isoquinolin-5-ones and their 2,3,10,10α-tetrahydrothiazolo[3,2-b]isoquinolin-5-one analogs. The tertiary N,O- and N,S-radicals formed upon aryl radical reaction at the ketene-N,X(X=O, S)-acetal double bond appear to have reasonable stability. The stereoselectivity in hydrogen abstractions by these intermediate radicals from both Bu₃SnH and (Me₃Si)₃SiH was investigated. The N,S-heterocyclic fused ring products may have potential medical value.     

6-endo Versus 5-exo radical cyclization: streamlined syntheses of carbahexopyranoses and derivatives by 6-endo-trig radical cyclization

Three factors that can direct 6-endo radical cyclization over 5-exo ring closure: substitution at C-5, vinyl radical cyclization and ring strain, have been considered in the context of the preparation of carbapyranoses from carbohydrate derivatives. As a result, alkyl radicals in substrates containing a strain inducing 2,3-O-isopropylidene ring, and vinyl radical in non-strained compounds undergo a completely regioselective 6-endo-trig ring closure leading to carbasugar derivatives.     

Synthesis of modified Weinreb amides: N-tert-butoxy-N-methylamides as effective acylating agents

An efficient preparation of N-methyl-O-tert-butylhydroxylamine hydrochloride has been settled, which allowed the synthesis of modified Weinreb amides. Nucleophilic addition of organolithium and Grignard reagents on these N-tert-butoxy-N-methylamides afforded efficiently the corresponding ketones and reduction with DIBAL furnished the corresponding aldehydes in good yields up to 97%.     

Identification and quantification of 13 components in Angelica sinensis (Danggui) by gas chromatography-mass spectrometry coupled with pressurized liquid extraction

Angelica sinensis (Danggui in Chinese), a well-known traditional Chinese medicine, is also used as a health food product for women's care in Europe and America. Therefore, the demand for Danggui is enormous throughout the world. Due to the shortage of Angelica sinensis, Angelica acutiloba and Angelica gigas are commonly used as the substitutes of Danggui in the market of southeast Asia. However, the three common Angelica roots showed variation in their genetic and chemical composition. Up to date, it is thought that ferulic acid, ligustilide and other phthalides such as butylidenephthalide are the biologically active components of Danggui. In this paper, the contents of 13 compounds including ferulic acid, Z-ligustilide, E-ligustilide, Z-butylidenephthalide, E-butylidenephthalide, 3-butylphthalide, 3-butylidene-4-hydroxyphthalide, senkyunolide A, 6,7-epoxyligustilide, senkyunolide F, senkyunolide H, senkyunolide I, and 6,7-dihydroxyligustilide were determined or estimated by using gas chromatography-mass spectrometry (GC-MS) coupled with pressurized liquid extraction (PLE). The results showed that GC-MS coupled with PLE offered a simple, rapid and high sensitive method to analysis of components in Angelica root. And the contents of investigated compounds in Angelica sinensis, Angelica acutiloba and Angelica gigas, which are used as Danggui in China, Japan and Korea, respectively, were highly variant. It is thought that interaction of multiple chemical compounds contributes to the therapeutic effects of Chinese medicines. However, the overall clinical efficacy of these different Danggui has not been determined. Therefore, comparison of chemical components and pharmacological activities of different Angelica root is helpful to elucidate the mechanism of therapeutic effects of Danggui.     

Conformational analysis of bridgehead-substituted bicyclo[m.m.m]alkanes and bicyclo[8.8.n]alkanes

Conformational analyses of bicyclo[m.m.m]alkanes where m=1-10 and of bicyclo[8.8.n]alkanes where n=1-7 bearing methyl groups on the bridgeheads were carried out using a Monte Carlo search strategy. In the bicyclo[m.m.m]alkane series, greater variability was observed for the inter-bridgehead distance for larger values of m. This suggests that properly substituted bicyclo[8.8.8]hexacosanes or larger ring systems might serve as molecular springs.     

An effective C-C double bond formation via Cu(I)-catalyzed dehydrogenation

A dehydrogenation method using Cu(I) and either N,N-di-tert-butylthiadiaziridine 1,1-dioxide or N,N-di-tert-butyldiaziridinone is reported. The dehydrogenation allows a facile introduction of C-C double bond(s) into various carbocycles and heterocycles such as oxazolines and thiazolines.     

A new, one-pot, three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines

A new, one-pot and three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines is described. The reactive 1:1 zwitterionic intermediate, formed by the addition of isocyanides to dialkyl acetylenedicarboxylates, was trapped by N-(2-heteroaryl)amides to yield a ketenimine intermediate, which was cyclized and then rearranged under the reaction conditions to afford the title compounds under mild reaction conditions in good yields. Single-crystal X-ray analysis conclusively confirms the structure of the obtained bridgehead bicyclic 6-6 heterocyclic compounds.