Two novel carbonic acid esters conjugated with oligophenyl glucosides from Rhamnus nakaharai

Two novel carbonic acid esters conjugated with oligomeric phenyl glycosides have been isolated and characterized from the wood of Rhamnus nakaharai. The structures are characterized as 5,7-dihydroxyphthalide 5-O-β-[6-O-{3″-methoxy-4″-O-β-[6?-O-(4?-O-carboxy-3?,5?-dimethoxy)phenyl]glucopyranosyl}phenyl]glucopyranoside (1) and 6-O-{3′-methoxy-4′-O-β-[6″-O-(3?-mercapto-5?-methoxy-4?-O-methylcarboxy)phenyl]glucopyranosyl}phenyl β-glucopyranose (2), namely, rhamnakoside A (1) and B (2), all by NMR and other spectral methods, respectively. They could be a novel case of phase II detoxification products and biogenetic diversity in plant kingdom.     

Optically active pentacyclic binuclear diorganotin compounds

Three optically active binuclear diorganotin compounds (2-4) were prepared from an optically active oxalamide: (1S,2R)-(−)-[N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N′-(2-hydroxy-phenyl)-oxalamide (1). The new compounds [1-(2′,2′-diorganyl-1′-oxa-3′-aza-2′-stanna-indan-3′-yl)-2-(2″,2″-diorganyl-4″-methyl-5″-phenyl[1,3,2]-oxazastannolidin-3″-yl)-ethane-1,2-dione {organyl = methyl (2), n-butyl (3) or phenyl (4)} were characterized by IR, elemental analysis and mass spectrometry. Compounds 3 and 4 were submitted to a detailed NMR study in order to assign their resonances (¹H and ¹³C) and specially the two different ¹¹⁹Sn signals for each compound. The X-ray diffraction analysis of compound 4 showed a planar pentacyclic framework with two penta-coordinated tin atoms with a distorted tbp geometry and 12 intramolecular hydrogen bonds.     

Total synthesis of apigenin 7,4′-di-O-β-glucopyranoside, a component of blue flower pigment of Salvia patens, and seven chiral analogues

We have succeeded in the first total synthesis of apigenin 7,4′-di-O-β-d-glucopyranoside (1a), a component of blue pigment, protodelphin, from naringenin (2). Glycosylation of 2 according to Koenigs-Knorr reaction provided a monoglucoside 4a in 80% yield, and this was followed by DDQ oxidation to give apigenin 7-O-glucoside (12a). Further glycosylation of 4′-OH of 12a with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl fluoride (5a) was achieved using a Lewis acid-and-base promotion system (BF₃·Et₂O, 2,6-di-tert-butyl-4-methylpyridine, and 1,1,3,3-tetramethylguanidine) in 70% yield, and subsequent deprotection produced 1a. Synthesis of three other chiral isomers of 1a, with replacement of d-glucose at 7 and/or 4′-OH by l-glucose (1b-d), and four chiral isomers of apigenin 7-O-β-glucosides (6a,b) and 4′-O-β-glucosides (7a,b) also proved possible.     

Aigialomycins and related polyketide metabolites from the mangrove fungus Aigialus parvus BCC 5311

Reinvestigation of the secondary metabolites from the marine mangrove fungus Aigialus parvus BCC 5311 led to the isolation of six new nonaketide metabolites, aigialomycins F (4) and G (5a/5b), 7′,8′-dihydroaigialospirol (7), 4′-deoxy-7′,8′-dihydroaigialospirol (8), and rearranged macrolides 9 and 10, along with six previously described compounds, hypothemycin (1), aigialomycins A (2) and B (3), aigialospirol (6), 4-O-demethylhypothemycin (11), and aigialone (12). The structures of the new compounds were elucidated by analyses of the NMR spectroscopic and mass spectrometry data in combination with chemical means.     

The microbiological transformation of steroidal saponins by Curvularia lunata

The microbiological transformation of polyphyllin I (compound I), polyphyllin III (compound II), polyphyllin V (compound III) and polyphyllin VI (compound IV) by Curvularia lunata into their corresponding subsaponins, for example, diosgenin-3-O-α-l-arabinofuranosyl (1→4)-β-d-glucopyranoside (compound V), diosgenin-3-O-α-l-rhamnopyranosyl (1→4)-β-d-glucopyranoside (compound VI), diosgenin-3-O-β-d-glucopyranoside (compound VII) and pennogenin-3-O-β-d-glucopyranoside (compound VIII), were studied in this paper. Curvularia lunata is able to hydrolyze terminal rhamnosyls that are linked by 1→2 C- bond to sugar residues of steroidal saponins at C-3 position with high activity and regioselectivity.     

Montamine, a unique dimeric indole alkaloid, from the seeds of Centaurea montana (Asteraceae), and its in vitro cytotoxic activity against the CaCo2 colon cancer cells

Reversed-phase HPLC analysis of the methanol extract of the seeds of Centaurea montana afforded a flavanone, montanoside (4), six epoxylignans, berchemol (7), berchemol 4′-O-β-d-glucoside (5), pinoresinol (10), pinoresinol 4-O-β-d-glucoside (8), pinoresinol 4,4′-di-O-β-d-glucoside (6), pinoresinol 4-O-apiose-(1→2)-β-d-glucoside (9), two quinic acid derivatives, trans-3-O-p-coumaroylquinic acid (1), cis-3-O-p-coumaroylquinic acid (2), and eight indole alkaloids, tryptamine (3), N-(4-hydroxycinnamoyl)-5-hydroxytryptamine (11), cis-N-(4-hydroxycinnamoyl)-5-hydroxytryptamine (12), centcyamine (16), cis-centcyamine (17), moschamine (13), cis-moschamine (14) and a dimeric indole alkaloid, montamine (15). While the structures of two new compounds, montanoside (4) and montamine (15), were established unequivocally by UV, IR, MS and a series of 1D and 2D NMR analyses, all known compounds were identified by comparison of their spectroscopic data with literature data. The antioxidant properties of these compounds were assessed by the DPPH assay, and their toxicity towards brine shrimps and cytotoxicity against CaCo-2 colon cancer cells were evaluated by the brine shrimp lethality and the MTT cytotoxicity assays, respectively. The novel dimer, montamine (15), showed significant in vitro anticolon cancer activity (IC₅₀=43.9 μM) while that of the monomer, moschamine (13), was of a moderate level (IC₅₀=81.0 μM).     

Proanthocyanidin glycosides from the leaves of Quercus ilex L. (Fagaceae)

From the polar extracts of the leaves of Quercus ilex L., two new proanthocyanidin glycosides, namely afzelechin-(4α→8)-catechin-3-O-β-glucopyranoside (1) and afzelechin-(4α→8)-catechin-3-O-α-rhamnopyranoside (2), were isolated in addition to catechin (3), proanthocyanidin B₃ (4), prodelphinidin C (5), dehydrodicatechin A (6), quercetin (7) and six known flavonol glucosides with their acylated derivatives (8-13) and ellagic acid (14). The structures of all isolated compounds were established by spectroscopic means, mainly 1D and 2D NMR, as well as LC/MS and HR-MS spectrometric analyses. The absolute configuration of compound 1 was determined by CD measurements. The proanthocyanidin glycosides are especially interesting, as they possess the sugar in the upper unit of the dimer, which is rare for this type of compounds.     

Novel antifungal polyene amides from the myxobacterium Cystobacter fuscus: isolation, antifungal activity and absolute structure determination

Three new unstable metabolites, (6E,10Z)-2′-O-methylmyxalamide D (1), 2′-O-methylmyxalamide D (2) and (6E)-2′-O-methylmyxalamide D (3) were isolated from the myxobacterium Cystobacter fuscus. The planar structures were elucidated by spectroscopic analyses to be geometrical isomers of a polyene amide related to a myxobacterial metabolite, myxalamide D (4). Their absolute stereochemistry was determined by synthesis of degradation products. Antifungal activities of 1-3 as well as their acetates were evaluated against the phythopathogenic fungus Phythopthora capsici.     

Synthetic studies on pterin glycosides: the first synthesis of 2′-O-(α-d-glucopyranosyl)biopterin

l-Rhamnose was led, in a 14-step-sequence, to N²-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (23), an appropriately protected precursor for 2′-O-glycosylation, while 4,6-di-O-acetyl-2,3-di-O-(4-methoxybenzyl)-α-d-glucopyranosyl bromide (32), a novel glycosyl donor, was efficiently prepared from d-glucose in 8 steps. The first synthesis of 2′-O-(α-d-glucopyranosyl)biopterin (2a) was achieved by treatment of the key intermediate 23 with 32 in the presence of silver triflate and tetramethylurea, followed by successive removal of the protecting groups.     

N-Nosyl as a stereoselectivity-improving and easily removable group in the O-glycosylation of d-allal and d-galactal-derived allyl aziridines. Stereospecific synthesis of 4-amino-2,3-unsaturated-O-glycosides

The glycosylation of alcohols, phenol, and partially protected monosaccharides with the diastereoisomeric d-allal and d-galactal-derived N-nosyl aziridines 2α and 2β leads to the corresponding 4-N-(nosylamino)-2,3-unsaturated-α-O- (6α) and β-O-glycosides and disaccharides (6β), respectively, in a stereospecific substrate-dependent O-glycosylation process. The N-(nosylamino) group of 6α and 6β can easily be deprotected to give the corresponding 4-amino-2,3-unsaturated-O-glycosides 7α and 7β, with an increased value to our glycosylation protocol.     

1→2 Migration and concurrent glycosidation of phenyl 1-thio-α-mannopyranosides via 2,3-O-cyclic dioxonium intermediates

Treatment of phenyl 2,3-O-cyclic ketene acetal- and 2,3-O-thionocarbonyl-1-thio-mannopyranosides with TMSOTf and MeOTf, respectively, gave the corresponding 2,3-O-cyclic dioxonium intermediates, which proceeded via 1→2 migration and concurrent glycosidation in the presence of alcohols to provide the corresponding 2-S-phenyl glycosides stereoselectively. While the former donors were too labile, the latter donors have proved superior for the present purpose. The X-ray crystallographic structures of phenyl 4-O-methyl-2,3-O-thiocarbonyl-1-thio-α-l-rhamnopyranoside (1), a typical donor for the present reaction, and its anomeric azide analogue (6), which could not undergo the present reaction under similar conditions, are provided.     

Synthesis of an ethidium nucleoside and its acyclic analog

The protected ethidium nucleosides 8-(3′,5′-di-O-benzoyl-2′-deoxy-d-ribofuranosyl)-3-acetamido-5-ethyl-6-phenyl-phenanthridinium (5), 8-(3′,5′-di-O-acetyl-2′-deoxy-d-ribofuranosyl)-3-acetamido-5-ethyl-6-phenyl-phenanthridinium (6), and the acyclic analog 8-[(3R)-1,3-dihydroxy-4-yl]-acetamido-3-amino-5-ethyl-6-phenyl-phenanthridinium (3) were prepared. Based on to their different stability, only the acyclic derivative 3 seems to be suitable for oligonucleotide synthesis. Furthermore, the acyclic ethidium nucleoside analog 3 exhibits comparable absorption and emission properties of the underivatized ethidium (1).     

Synthesis and structural characterization of η-allyl(α-diimine)nickel(II) complexes bearing trimethylsilyl groups

A set of isomeric para- and meta-trimethylsilylphenyl ortho-substituted N,N-phenyl α-diimine ligands [(Ar-NC(Me)-(Me)CN-Ar) Ar=2,6-di(4-trimethylsilylphenyl)phenyl (16); Ar=2,6-di(3-trimethylsilylphenyl)phenyl (17)] have been synthesized through a two-step procedure. The palladium-catalysed cross-coupling reaction between 2,6-dibromophenylamine (7) and 4-trimethylsilylphenylboronic acid (8), 3-trimethylsilylphenylboronic acid (9) was used to prepare 4,4^′-bis(trimethylsilyl)-[1,1^′;3^′,1″]terphenyl-2^′-ylamine (10) and 3,3^′-bis(trimethylsilyl)-[1,1^′;3^′,1″]terphenyl-2^′-ylamine (11). The di-1-adamantylphosphine oxide Ad₂P(O)H (13) and di-tert-butyl-trimethylsilylanylmethylphosphine tert-Bu₂P-CH₂-SiMe₃ (14) were used for the first time as ligands for the Suzuki coupling. The condensation of 2,2,3,3-tetramethoxybutane (15) with anilines 10 and 11 afforded α-diimines 16 and 17. The reaction of π-allylnickel chloride dimer (18), α-diimines (16), (17) and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BAF) (19) or silver hexafluoroantimonate (20) led to two sets of isomeric complexes [η³-allyl(Ar-NC(Me)-(Me)CN-Ar)Ni]⁺ X⁻, [Ar=2,6-di(4-trimethylsilylphenyl)phenyl, X=BAF (3), X=SbF₆ (4); Ar=2,6-di(3-trimethylsilylphenyl)phenyl, X=BAF (5), X=SbF₆ (6)]. The steric repulsion of closely positioned trimethylsilyl groups in 4 caused the distortion of the nickel square planar coordination by 17.6° according to X-ray analysis.     

Synthesis of (E)-diethyl 6,6′-(diazene-1,2-diyl)bis(5-cyano-2-methyl-4-phenylnicotinates), a new type of 2,2′-azopyridine dyes

An unexpected, but simple method for the efficient synthesis of new 2.2′-azopyridine dyes, such as (E)-diethyl 6,6′-(diazene-1,2-diyl)bis(5-cyano-2-methyl-4-phenylnicotinates) (2, 4, 6, 8, 10, and 12), based on the treatment of ethyl 6-amino-5-cyano-2-methyl-4-arylnicotinates (1, 3, 5, 7, 9, and 11) with NBS/benzoyl peroxide, is described. The X-ray diffraction analysis and the UV-vis absorption spectra of dye 2 are reported and discussed.     

An unexpected formation of pyrazolopyrimidines during the attempted to obtain 5-substituted tetrazoles from carbonitriles

In this Letter, we described the synthesis of new 5-(5-amino-1-aryl-1H-pyrazole-4-yl)-1H-tetrazoles 2a–c from 5-amino-1-aryl-1H-pyrazole-4-carbonitriles 1a–c as well as the unexpected 1H-pyrazolo[3,4-d]pyrimidine derivatives 6a–c from 5-amino-1-aryl-3-methyl-1H-pyrazole-4-carbonitriles 4a–c, instead of 5-(5-amino-1-aryl-3-methyl-1H-pyrazole-4-yl)-1H-tetrazoles 5a–c as desired. In an attempt to obtain these tetrazole derivatives containing the methyl group at C3-position in the pyrazole ring, the amino group in 5-amino-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile 4c was protected by the reaction with sodium hydride and di-tert-butyl-dicarbonate (Boc). The tetrazole derivative 5c was synthesized from the protected compound 7c using analogue methodology to obtain 2a–c and 6a–c.     

Synthesis of (3′R,5′S)-3′-hydroxycotinine using 1,3-dipolar cycloaddition of a nitrone

To synthesize (3′R,5′S)-3′-hydroxycotinine [(+)-1], the main metabolite of nicotine (2), cycloaddition of C-(3-pyridyl)nitrones 3a, 3c, and 15 with (2R)- and (2S)-N-(acryloyl)bornane-10,2-sultam [(2R)- and (2S)-8] was examined. Among them, l-gulose-derived nitrone 15 underwent stereoselective cycloaddition with (2S)-8 to afford cycloadduct 16, which was elaborated to (+)-1.     

The synthesis of R-3-alkoxy-1-(1′-hydroxyethyl)-4-methoxy-2-(1″-propenyl)benzenes utilizing Corey-Bakshi-Shibata asymmetric reductions

Pyrolysis of the 3-O-allyl derivative 7 of isovanillin followed by alkylation of the derived allylphenol 8 afforded a series of benzaldehyde derivatives 9-11 each of which was transformed by initial treatment with methylmagnesium bromide followed by oxidation of the corresponding alcohols with activated manganese dioxide into a series of ketones 15-17. Palladium(0) catalysed isomerization of the double bond in the prop-2′-enyl side-chain afforded ketones 36-38 which were subjected to the Corey-Bakshi-Shibata asymmetric reduction protocol to afford the R-3-alkoxy-1-(1′-hydroxyethyl)-4-methoxy-2-(1″-propenyl) benzenes 42-44 in yields of approximately 60% and with ee's of 75%.     

A facile synthesis of pyrrolo[1,2-a]benzimidazoles and pyrazolo[3,4:4′,3′]pyrrolo[1,2-a]benzimidazole derivatives

Reaction of 2-cyanomethylbenzimidazole 1 with hydrazonoyl halides 2 led to formation of pyrrolo[1,2-a]benzimidazole derivatives 7. Similar reaction of 1 with halides 3 afforded 5-amino-4-(benzimidazol-2-yl)pyrazole derivatives 11 or 1-amino-2-arylpyrazolo[3,4:4′,3′]pyrrolo[1,2-a]benzimidazol-4-one 14 depending on the reaction conditions. The mechanisms of the studied reactions are discussed.     

A convenient synthesis of substituted 2,2′:6′,2″-terpyridines

The 2,2′:6′,2″-terpyridines 7a-c were prepared in good yield by reacting α-acetoxy-α-chloro-β-keto-esters 3a-c with bis-amidrazone 4 and 2,5-norbornadiene 6 in ethanol at reflux. Compounds 3a and 3b gave the 2,2′:6′,2″-terpyridines 9a and 9b, respectively, in moderate yield when treated with compound 4 and enamine 8.     

Synthesis of novel photolabile glycosides from methyl 4,6-O-(o-nitro)benzylidene-α-d-glycopyranosides

Novel photolabile sugar derivatives bearing a 4- or 6-O-(o-nitro)benzyl group have been prepared from the corresponding methyl 4,6-O-(o-nitro)benzylidene α-d-glycopyranosides. Regioselective cleavage with BF₃·Et₂O/Et₃SiH led to the methyl 6-O-(o-nitro)benzyl gluco- and manno-α-d-glycopyranosides 3 and 6. Inversion of configuration at 4-OH position of gluco and manno derivatives offered the otherwise inaccessible methyl 6-O-(o-nitro)benzyl galacto- and talo-α-d-glycopyranosides 4, 5, and 7. Careful reaction with PhBCl₂/Et₃SiH (3 equiv of reagents, 10 min at −78 °C) led to the desired methyl 4-O-(o-nitro)benzyl gluco- and manno-α-d-glycopyranosides 8 and 9 in very good yield. However, prolonged reaction with 6 equiv of PhBCl₂/Et₃SiH transformed the methyl 4,6-O-(o-nitro)benzylidene α-d-glucopyranoside 11 into the reduced d-glucitol derivative 15. Oxidative cleavage of 5,6-diol function of 15 gave the corresponding photolabile l-xylose 17. The photolabile glucosides 3 and 8 have been further transformed into the photolabile α-C-allyl d-glucopyranosides 20 and 22.