Nickel-catalyzed alkylation of ketones and nitriles with primary alcohols.

Nickel(II)-salen or nickel(II)-salphen catalyzed α-alkylation of ketones and nitriles with primary alcohols is reported. Various α-alkylated ketones and nitriles were obtained in high yields through a borrowing hydrogen strategy by using 1-3 mol% of nickel catalyst and a catalytic amount of NaOH (5-10 mol%) under aerobic conditions.

Tuning the selectivity in iridium-catalyzed acceptorless dehydrogenative coupling of primary alcohols.

An acceptorless dehydrogenative coupling of primary alcohols to carboxylic acids/carboxylates, esters, and Guerbet alcohols (via both homo- and cross-ß-alkylation of the alcohols) in the presence of an N-heterocyclic carbene iridium(I) catalyst was developed under aerobic conditions. The product selectivity can be easily tuned among the products with a single catalyst through simple modification of the reaction conditions, such as the catalyst and base amounts, the choice of base, and the reaction temperature.

Synthesis of α-Alkylated Ketones via Selective Epoxide Opening/Alkylation Reactions with Primary Alcohols.

A new method for converting terminal epoxides and primary alcohols into α-alkylated ketones under borrowing hydrogen conditions is reported. The procedure involves a one-pot epoxide ring opening and alkylation via primary alcohols in the presence of an N-heterocyclic carbene iridium(I) catalyst, under aerobic conditions, with water as the side product.

Iridium-Catalyzed Alkylation of Secondary Alcohols with Primary Alcohols: A Route to Access Branched Ketones and Alcohols.

Under borrowing hydrogen conditions, NHC-iridium(I) catalyzed the direct or one-pot sequential synthesis of α,α-disubstituted ketones via the alkylation of secondary alcohols with primary alcohols is reported. Notably, the present approach provides a new method for the facile synthesis of α,α-disubstituted ketones and featured with several characteristics, including a broad substrate scope, using easy-to-handle alcohols as starting materials, and performing the reactions under aerobic conditions. Moreover, the selective one-pot formation of ß,ß-disubstituted alcohols was achieved by the addition of an external hydrogen source to the reaction mixture.

Iridium(I)-Catalyzed C-C and C-N Bond Formation Reactions via the Borrowing Hydrogen Strategy.

Iridium(I) complexes having an imidazol-2-ylidene ligand with benzylic wingtips efficiently catalyzed the ß-alkylation of secondary alcohols with primary alcohols and acceptorless dehydrogenative cyclization of 2-aminobenzyl alcohol with ketones through a borrowing hydrogen pathway. The ß-alkylated alcohols, including cholesterol derivatives, and substituted quinolines were obtained in good yields by using a minute amount of the catalyst with a catalytic amount of NaOH or KOH under the air atmosphere, liberating water (and H2 in the case of quinoline synthesis) as the sole byproduct. Notably, this system demonstrated turnover numbers of 940 000 (for ß-alkylation of secondary alcohols with primary alcohols by using down to 0.0001 mol % = 1 ppm of the catalyst) and 9200 (acceptorless dehydrogenative cyclization of 2-aminobenzyl alcohol with ketones).

Iridium(I)-Catalyzed Alkylation Reactions To Form α-Alkylated Ketones.

A highly effective and green procedure for the formation of α-alkylated ketones has been disclosed via the reaction of primary alcohols with secondary alcohols and ketones by using [IrCl(COD)(NHC)] complexes as a catalyst. Various α-alkylated ketones were obtained in high yields from the alkylation of alcohol with alcohol and ketone with alcohol through a borrowing hydrogen reaction by using 0.05-0.5 mol % iridium(I) and a catalytic amount of KOH (5-10 mol %) as the base under air atmosphere and within very short reaction times.

Secondary metabolites from Astragalus karjaginii BORISS and the evaluation of their effects on cytokine release and hemolysis.

A new cycloartane sapogenol and a new cycloartane xyloside were isolated from Astragalus karjaginii BORISS along with thirteen known compounds. The structures of the new compounds were established as 3-oxo-6α,16ß,24(S),25-tetrahydroxycycloartane (1) and 6-O-ß-d-xylopyranosyl-3ß,6α,16ß,24(S),25-pentahydroxycycloartane (2) by 1D- and 2D-NMR experiments as well as ESIMS and HRMS analyses. The presence of the keto function at position 3 was reported for the first time for cyclocanthogenol sapogenin of Astragalus genus. In vitro immunomodulatory effects of the new compounds (1 and 2) along with the n-BuOH and MeOH extracts of A. karjaginii at two different doses (3 and 6µg) were tested on human whole blood for in vitro cytokine release (IL-2, IL-17A and IFN-γ) and hemolytic activities. The results confirmed that compound 2, a monodesmosidic saponin, had the strongest effect on the induction of both IL-2 (6µg, 6345.41±0.12pg/mL (×5), P<0.001) and a slight effect upon IL-17A (3µg, 5217.85±0.72pg/mL, P<0.05) cytokines compared to the other test compounds and positive controls (AST VII: Astragaloside VII; and QS-21: Quillaja saponin 21). All tested extracts and molecules also induced release of IFN-γ remarkably ranging between 5031.95±0.05pg/mL, P<0.001 for MeOH extract (6µg) and 5877.08±0.06pg/mL, P<0.001 for compound 1 (6µg) compared to QS-21 (6µg, 5924.87±0.1pg/mL, P<0.001). Administration of AST VII and other test compounds did not cause any hemolytic activity, whereas QS-21 resulted a noteworthy hemolysis.

Acceptorless Dehydrogenative Oxidation of Secondary Alcohols Catalysed by Cp*Ir(III) -NHC Complexes.

A series of new Ir(III) complexes with carbene ligands that contain a range of benzyl wingtip groups have been prepared and fully characterised by NMR spectroscopy, HRMS, elemental analysis and X-ray diffraction. All the complexes were active in the acceptorless dehydrogenation of alcohol substrates in 2,2,2-trifluoroethanol to give the corresponding carbonyl compounds. The most active complex bore an electron-rich carbene ligand; this complex was used to catalyse the highly efficient and chemoselective dehydrogenation of a wide range of secondary alcohols to their respective ketones, with turnover numbers up to 1660. Mechanistic studies suggested that the turnover of the dehydrogenation reaction is limited by the H2 -formation step.

Oleanane-type glycosides from Tremastelma palaestinum (L.) Janchen.

Three new oleanane-type glycosides, 1-3, were isolated from the whole plant of Tremastelma palaestinum (L.) Janchen, along with eight known triterpene glycosides. The structures of the new compounds were established as 3-O-[ß-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→3)-ß-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl]hederagenin (1), 3-O-[ß-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→3)-ß-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl]hederagenin 28-O-ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl ester (2), and 3-O-[α-l-rhamnopyranosyl-(1→3)-ß-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl]oleanolic acid 28-O-ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranosyl ester (3) by using 1D- and 2D-NMR techniques and mass spectrometry. This is the first report on the phytochemical investigation of a species belonging to Tremastelma genus.

Cycloartane glycosides from Astragalus plumosus var. krugianus and evaluation of their antioxidant potential.

The methanol extracts of Astragalus plumosus var. krugianus Chamb. & Matthews afforded sixteen cycloartane glycosides among which krugianoside A, was never reported before. All compounds were evaluated for their cytotoxic activity in human skin fibroblast WS1 cells. For compounds exhibiting no significant effect on WS1 viability, the antioxidant potential was examined. Compounds 1 and 8 prevented elevation of ROS induced by t-BOOH, suggesting the potential activity of these compounds to protect fibroblasts from oxidative stress.

Oleanane type glycosides from Paronychia anatolica subsp. balansae.

Four new oleanane-type triterpene glycosides were isolated from the methanol extract of the roots of Paronychia anatolica subsp. balansae along with three known oleanane-type triterpene glycosides. Structures of the new compounds were established as 3-O-ß-D-glucuronopyranosyl-28-O-[α-L-rhamnopyranosyl-(1→2)-ß-D-quinovopyranoside] zahnic acid, 3-O-ß-D-glucuronopyranosyl-28-O-[ß-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-ß-D-quinovopyranoside] zahnic acid, 3-O-ß-D-glucuronopyranosyl-28-O-[α-L-arabinofuranosyl-(1→2)-ß-D-quinovopyranoside] zahnic acid, 28-O-[α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl]-medicagenic acid, by using 1D and 2D-NMR techniques and mass spectrometry. The cytotoxic activity of the isolated compounds was evaluated against a small panel of cancer cell lines including human breast cancer (MCF-7), human lung adenocarcinoma (A549) and human leukemia (U937) cell lines.

Unusual secondary metabolites from Astragalus halicacabus LAM.

From the whole plant of Astragalus halicacabus (Sect. Halicacabus), a new cycloartane-type glycoside, (20R,24S)-3-O-[α-L-arabinopyranosyl-(1→2)-ß-D-xylopyranosyl]-20,24-epoxy-16-O-ß-D-glucopyranosyl-3ß,6α,16ß,25-tetrahydroxycycloartane, and a new glycoside, 3-O-[ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranosyl]maltol were isolated together with seven known cycloartane-type glycosides, i.e., cyclocanthoside D, askendosides D, F, and G, cyclosieversioside G, cyclostipuloside A, elongatoside, and a known maltol glucoside, 3-O-ß-D-glucopyranosylmaltol. The structures were elucidated by means of high-resolution mass spectrometry, and extensive 1D- and 2D-NMR spectroscopic analysis. This is the first phytochemical work on A. halicacabus, and a maltol glycoside was encountered for the first time in the Leguminosae family.

Oleanane glycosides from Astragalus tauricolus: isolation and structural elucidation based on a preliminary liquid chromatography-electrospray ionization tandem mass spectrometry profiling.

As a part of our ongoing research for bioactive compounds from Turkish Astragalus species, the investigation of Astragalus tauricolus has been carried out. An approach based on HPLC-ESIMS(n) experiments has been used to profile the triterpene glycosides occurring in the butanol extract of the whole plant. On the basis of the results of the online screening by HPLC-ESIMS(n), 22 oleanane-type triterpene glycosides, including ten compounds never reported before, were isolated, and their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analysis. Noteworthy, cycloartane-type triterpene glycosides, the main constituents of Astragalus spp., were not found. This peculiar feature characterizes a very limited group of Astragalus spp. The antiproliferative activity of the isolated compounds 1-12, 15, 17-19 was evaluated against a small panel of cancer cell lines. Only compound 11 showed an IC(50) of 22 µM against human leukemia cell line (U937). The other tested compounds, in a range of concentrations between 1 and 50 µM, did not cause any significant reduction of the cell number.

Triterpene glycosides from Astragalus angustifolius.

Six new cycloartane-type (1- 6) and four new oleanane-type (7- 10) triterpene glycosides were isolated from Astragalus angustifolius Lam., together with five known triterpene glycosides. Their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analysis. Compounds 1- 3 are glycosides of cycloastragenol, while compounds 4- 6 show the C-24 epimer of cycloastragenol as aglycone, encountered for the first time in nature. All compounds were evaluated for their antiproliferative activity in Hela, H-446, HT-29, and U937 cell lines. Only compound 8 displayed a weak activity with IC (50) values of 36 and 50 µM against Hela and HT-29 cell lines, respectively.

Triterpene saponins from Cyclamen hederifolium.

Five triterpene saponins never reported before, hederifoliosides A-E, and four known triterpene saponins were isolated from the tubers of Cyclamen hederifolium. The structures of hederifoliosides A-E were determined as 3ß,16α-dihydroxy-13ß,28-epoxyolean-30-oic acid 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 3ß,16α-dihydroxy-13ß,28-epoxyolean-30-oic acid 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)]-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 3ß,16α-dihydroxy-13ß,28-epoxyolean-30-al 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)]-O-[ß-D-glucopyranosyl-(1 → 6)]-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 30-O-ß-D-glucopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-3ß,16α,30-trihydroxyolean-12-en-28-al 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 30-O-ß-D-glucopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-3ß,16α,28,30-tetrahydroxyolean-12-en 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)]-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, by a combination of one- and two-dimensional NMR techniques, and mass spectrometry. The cytotoxic activity of the isolated compounds was evaluated against a small panel of cancer cell lines including Hela, H-446, HT-29, and U937. None of the tested compounds, in a range of concentrations between 1 and 50 µM, caused a significant reduction of the cell number.

Cycloartane glycosides from Astragalus aureus.

Eight cycloartane-type triterpene glycosides (1-8) were isolated from Astragalus aureus Willd along with ten known cycloartane-type glycosides (9-18). Their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analyses. Compounds 1-5 are cyclocanthogenin glycosides, whereas compounds 6-8 are based on cyclocephalogenin as aglycon, more unusual in the plant kingdom, so far reported only from Astragalus spp. Moreover, for the first time monoglycosides of cyclocanthogenin (5) and cyclocephalogenin (7, 8) are reported. All of the compounds tested for their cytotoxic activities against a number of cancer cell lines. Among the compounds, only 8 exhibited activity versus human breast cancer (MCF7) at 45 µM concentration.

Phenolic Glycosides with antiproteasomal activity from Centaurea urvillei DC. subsp. urvillei.

A new flavanone glycoside, naringenin-7-O-ß-D-glucuronopyranoside, and a new flavonol glycoside, 6-hydroxykaempferol-7-O-ß-D-glucuronopyranoside were isolated together with 12 known compounds, 5 flavone glycoside; hispidulin-7-O-ß-D-glucuronopyranoside, apigenin-7-O-ß-D-methylglucuronopyranoside, hispidulin-7-O-ß-D-methylglucuronopyranoside, hispidulin-7-O-ß-D-glucopyranoside, apigenin-7-O-ß-D-glucopyranoside, a flavonol; kaempferol, two flavone; apigenin, and luteolin, a flavanone glycoside; eriodictyol-7-O-ß-D-glucuronopyranoside, and three phenol glycoside; arbutin, salidroside, and 3,5-dihydroxyphenethyl alcohol-3-O-ß-D-glucopyranoside from Centaurea urvillei subsp. urvillei. The structure elucidation of the new compounds was achieved by a combination of one- ((1)H and (13)C) and two-dimensional NMR techniques (G-COSY, G-HMQC, and G-HMBC) and LC-ESI-MS. The isolated compounds were tested for their antiproteasomal activity. The results indicated that kaempferol, a well known and widely distributed flavonoid in the plant kingdom, was the most active antiproteasomal agent, followed by apigenin, eriodictyol-7-O-ß-D-glucuronopyranoside, 3,5-dihydroxyphenethyl alcohol-3-O-ß-D-glucopyranoside, and salidroside, respectively.

Alpha-glucosidase inhibitory constituents of Linaria kurdica subsp. eriocalyx.

Three known iridoid glycosides, antirrhide (1), antirrhinoside (2), and 5-O-beta-allosylantirrhinoside (3), and two known flavone glycosides, linariin (4"'-O-acetylpectolinarin) (4) and linarin (acacetin-7-O-beta-D-rutinoside) (5) were isolated from Linaria kurdica Boiss & Hohen. subsp. eriocalyx. The structures of the isolated compounds were established from spectroscopic evidence. Compounds 1-3 showed high inhibitory potential against alpha-glucosidase.

Monoterpenoid glucoindole alkaloids and iridoids from Pterocephalus pinardii.

A new secondary metabolite, pterocephaline, along with the known cantleyoside, 7alpha-morroniside, 3beta,5alpha-tetrahydrodesoxycordifoline lactam, 5S-5-carboxyvincoside, sweroside, and loganin have been isolated from the aerial parts of P. pinardii (Dipsacaceae). Moreover, cantleyoside-methyl-hemiacetal and cantleyoside-dimethyl-acetal were obtained as seco-iridoid artifacts. The structures were elucidated by extensive spectroscopic methods including 1D-((1)H, (13)C and TOCSY) and 2D-NMR (DQF-COSY, HSQC and HMBC). Monoterpenoid glucoindole alkaloids were encountered for the first time in Dipsacaceae family.