Unusual Substitution Research Articles

Onions: A Source of Unique Dietary Flavonoids

Onion bulbs (Allium cepa L.) are among the richest sources of dietary flavonoids and contribute to a large extent to the overall intake of flavonoids. This review includes a compilation of the existing qualitative and quantitative information about flavonoids reported to occur in onion bulbs, including NMR spectroscopic evidence used for structural characterization. In addition, a summary is given to index onion cultivars according to their content of flavonoids measured as quercetin. Only compounds belonging to the flavonols, the anthocyanins, and the dihydroflavonols have been reported to occur in onion bulbs. Yellow onions contain 270-1187 mg of flavonols per kilogram of fresh weight (FW), whereas red onions contain 415-1917 mg of flavonols per kilogram of FW. Flavonols are the predominant pigments of onions. At least 25 different flavonols have been characterized, and quercetin derivatives are the most important ones in all onion cultivars. Their glycosyl moieties are almost exclusively glucose, which is mainly attached to the 4', 3, and/or 7-positions of the aglycones. Quercetin 4'-glucoside and quercetin 3,4'-diglucoside are in most cases reported as the main flavonols in recent literature. Analogous derivatives of kaempferol and isorhamnetin have been identified as minor pigments. Recent reports indicate that the outer dry layers of onion bulbs contain oligomeric structures of quercetin in addition to condensation products of quercetin and protocatechuic acid. The anthocyanins of red onions are mainly cyanidin glucosides acylated with malonic acid or nonacylated. Some of these pigments facilitate unique structural features like 4'-glycosylation and unusual substitution patterns of sugar moieties. Altogether at least 25 different anthocyanins have been reported from red onions, including two novel 5-carboxypyranocyanidin-derivatives. The quantitative content of anthocyanins in some red onion cultivars has been reported to be approximately 10% of the total flavonoid content or 39-240 mg kg (-1) FW. The dihydroflavonol taxifolin and its 3-, 7-, and 4'-glucosides have been identified in onions. Although the structural diversity of dihydroflavonols characterized from onions is restricted compared with the wide structural assortment of flavonols and anthocyanins identified, they may occur at high concentrations in some cultivars. From bulbs of the cultivar "Tropea", 5.9 mg of taxifolin 7-glucoside and 98.1 mg of taxifolin have been isolated per kilogram of FW.

Description of two new HLA‐C alleles in a Black South African population

Two new HLA-C alleles, Cw*0333 and Cw*0217, were identified in a Black South African population. HLA-Cw*0333 differs from Cw*030201 by an A-->G substitution at nucleotide 323, yielding an unusual missense substitution of Cys for the conserved Tyr-84 at the antigen cleft terminus. Molecular modeling suggests that this alters the predicted interactions of this critical residue with the opposite alpha(2)-helix, the peptide COOH terminus and possibly KIR2DL2. The second allele, Cw*0217, differs from Cw*0205 by an A-->T substitution at nucleotide 368, resulting in a Tyr-->Phe substitution at residue 99 of the HLA-C beta-pleated sheet that likely influences peptide side-chain binding. Both Cw*0333 and Cw*0217 appear to have arisen by missense mutations, respectively, from the HLA-B*5801-Cw*0302 and B*080101-Cw*0205 haplotypes.

Grandfather Effects: A Longitudinal Case Study of the Phonological Acquisition of Intervocalic Consonants in English

In this article, I present a longitudinal study of a child's (male, aged 3;0–3;4) acquisition of intervocalic consonants characterized within the framework of Optimality Theory (OT). At Stage I, the child presents with unusual error patterns, weakening and labial substitution, and shows evidence of phonologically opaque surface forms. These patterns persist at Stage II despite elaboration of phonemic contrasts intervocalically. In addition, a new error pattern emerges, nasal harmony, along with additional opaque forms. Although the errors exhibited by the child are somewhat atypical of those generally observed in acquisition, they are, nevertheless, entirely consistent with cross-linguistic facts. Further, although phonological opacity is a linguistic phenomenon that poses a challenge to nonderivational theoretical frameworks such as OT, I offer McCarthy's (2002; 2003a) comparative markedness approach as a solution to this problem that is theoretically superior to alternatives.

Hemoglobin structure/function and globin-gene evolution in the Arctic fish Liparis tunicatus

The importance of the Arctic, in contributing to the knowledge of the overall ensemble of adaptive processes influencing the evolution of marine organisms, calls for investigations on molecular adaptations in Arctic fish. Unlike the vast majority of Antarctic Notothenioidei, several Arctic species display high hemoglobin multiplicity. The blood of four species, the spotted wolffish of the family Anarhichadidae and three Gadidae, contains three functionally distinct major components. Similar to many Antarctic notothenioids, Arctic Liparis tunicatus (suborder Cottoidei, family Liparidae) has one major hemoglobin (Hb 1) accompanied by a minor component (Hb 2). This paper reports the structural and functional characterisation of Hb 1 of L. tunicatus. This hemoglobin shows low oxygen affinity, and pronounced Bohr and Root effects. The amino-acid sequence of the β chain displays an unusual substitution in NA2 (β2) at the phosphate-binding site, and the replacement of Val E11 (β67) with Ile. Similar to some Antarctic fish Hbs, electron paramagnetic resonance spectra reveal the formation of a ferric penta-coordinated species even at physiological pH. The amino-acid sequences have also been used to gain insight into the evolutionary history of globins of polar fish. L. tunicatus globins appear close to the notothenioid clades as predicted by teleostean phylogenies. Close phylogenetic relationships between Cottoidei and Notothenioidei, together with their life style, seem to be the main factor driving the globin-sequence evolution.

Bioactive Natural Products from the Endophytic Fungus Ascochyta sp. from Meliotus dentatus – Configurational Assignment by Solid‐State CD and TDDFT Calculations

AbstractTwo new metabolites, (4S)‐(+)‐ascochin (1a) and (S,S)‐(+)‐ascodiketone (3), together with the known compounds (3R,4R)‐(–)‐4‐hydroxymellein (2), ent‐α‐cyperone (4) and (3S,4R)‐(–)‐dihydroxy‐(6S)‐undecyl‐α‐pyranone (5) were isolated from cultures of the of the endophytic fungus Ascochyta sp. The biologically active isocoumarin derivative, (4S)‐(+)‐ascochin (1a), has an unusual substitution pattern which was confirmed by X‐ray diffraction. Its absolute configuration was determined by our solid‐state TDDFT CD methodology using the X‐ray coordinates as input for the calculation. By catalytic hydrogenation, (4S)‐(+)‐ascochin was converted into the corresponding (3S,4S)‐dihydroisocoumarin derivative 1b. The measured and TDDFT calculated CD spectra enabled studies on the correlation between absolute configuration and n‐π* transition Cotton effect. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

A nucleotide sequence variation detection system for the core region of hepatitis C virus-1b

Amino-acid substitution at positions 70 and 91 of the hepatitis C virus (HCV)-1b core region is a factor that contributes to a non-virological response in treatment using interferon/ribavirin combination. In this study, a system was developed for detection of nucleotide sequence variation in the core region that is simpler and less expensive than the current direct sequencing method. A PCR detection method using mutation-specific primers was developed, and amino acids at positions 70 and 91 were identified. The protein type was determined based on band intensity in electrophoresis, and classified into wild (70:R, 91:L), mutant (70:Q/H, 91:M) and competitive types. The detection rate, sensitivity and reproducibility were investigated in 108 patients with HCV-1b who were treated with interferon/ribavirin combination therapy, and correlation with the results of direct sequencing was examined. The detection rate was 94.4%, the sensitivity was 10 KIU/mL, the reproducibility was high, and in detectable cases the consistency with direct sequencing was 97.1%; inconsistency was noted in two competitive-type cases and in one case with an unusual amino-acid substitution. The results suggest that the system described in this paper provides an effective, simple and low-cost approach to detection of nucleotide sequence variation in the core region of HCV-1b.

Nucleophilic substitution at the anomeric position of 1,2- O-isopropylidenefuranose derivatives. A novel stereoselective synthesis of cyclic phosphates analogous to cAMP

1,2- O-Isopropylidenefuranose derivatives were treated with various nucleophiles in the presence of either BF 3·OEt 2 or trimethylsilyl trifluoromethanesulfonate (TMSOTf) leading to substitution products in a regio- and stereoselective manner. In particular, nucleophilic substitution of 1,2- O-isopropylidenefuranose derivatives when treated with allyltrimethylsilane was controlled by steric and electronic factors (similar to Woerpel’s stereoelectronic model). On the other hand, when 1,2- O-isopropylidenefuranose derivatives were treated with trimethylsilane, in the presence of bis- O-trimethylsilyl-5-iodouracil or bis- O-trimethylsilyl-thymidine, substitution products were generated in high regio- and stereoselectivities via an unusual nucleophilic substitution with opening of the furanose ring. Based on these results, a stereoselective method for the synthesis of neutral cyclic phosphates analogous to cAMP was developed.

Detection of Hepatitis B Virus (HBV) Genotype E Carried—Even in the Presence of High Titers of Anti-HBs Antibodies—by an Argentinean Patient of African Descent Who Had Received Vaccination against HBV

Genotype E hepatitis B virus (HBV) was detected in two Argentine sisters exhibiting an African mitochondrial lineage. One of them (who had been vaccinated against HBV) exhibited anti-HBs cocirculating antibodies without HBsAg escape mutants, while her unvaccinated sister showed a D144A HBsAg escape mutant without anti-HBs antibodies. Both sisters carried an unusual L209V substitution within HBsAg.

Relative Potential for Selection of Quinolone-Resistance- Determining-Region Mutations in Streptococcus pneumoniae by Gemifloxacin, Gatifloxacin and Moxifloxacin

Serial passage of a clinical isolate of Streptococcus pneumoniae, in the presence of moxifloxacin, gatifloxacin or gemifloxacin, gave rise to resistant isolates. Non-susceptibility as defined by Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) breakpoints arose on Days 10, 11, and 12 with gatifloxacin, gemifloxacin, and moxifloxacin respectively. Moxifloxacin and gatifloxacin selected for a single step quinolone-resistant-determining-region (QRDR) mutation in DNA gyrase (GyrA) on Day 4 and 7 respectively, whereas gemifloxacin selected simultaneously for multi-step mutations in gyrase and topoisomerase IV (ParC) on Day 17 and activated a non-reserpine inhibited efflux mechanism by Day 4. As found in clinical isolates, mutations included Ser-81-Phe and Glu-85-Lys in GyrA and Ser-79- Phe or Asp-83-Tyr in ParC. At high MICs, moxifloxacin showed a previously unreported 4 amino-acid deletion in GyrB as well as a more unusual substitution Ser-79-Leu/Ile in ParC. Gemifloxacin showed a 2- to 16-fold greater activity than moxifloxacin or gatifloxacin against strains with two or more QRDR mutations, however, its potency did not translate to nonsusceptibility and gemifloxacin MIC values were either at or well above the CLSI nonsusceptible breakpoint concentration.

Insecticidal Activity of Paraherquamides, Including Paraherquamide H and Paraherquamide I, Two New Alkaloids Isolated from Penicillium cluniae

Paraherquamide H (1) and paraherquamide I (2), two new compounds of the paraherquamide (PHQ) family, together with the already known paraherquamide A (3), paraherquamide B (4), paraherquamide E (5), VM55596 (N-oxide paraherquamide) (6), paraherquamide VM55597 (7), and five known diketopiperazines (8-12) have been isolated from the culture broth of Penicillium cluniae Quintanilla. The structure of 1 and 2, on the basis of NMR and MS analysis, was established. It is worth noticing that, in both cases, an unusual oxidative substitution in C-16 was found, which had only previously been detected in PHQ 7. Isolated compounds were tested for insecticidal activity against the hemipteran Oncopeltus fasciatus Dallas. Mortality data have allowed preliminary structure activity relationships to be proposed. The most potent product was 5 with a LD(50) of 0.089 microg/nymph.

Syntheses, Structure, and Bonding of Rb14(Mg1‐xInx)30. A Nonstoichiometric Phase with an Unusual Substitution in the Anion Framework.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Selective Ring‐Opening of Nonactivated Amino Aziridines by Thiols and Unusual Nucleophilic Substitution of a Dibenzylamino Group.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

AVOIDING A DOSE OF YOUR OWN MEDICINE

How do venomous animals or plants protect themselves from their own poisons? This question must have occurred to everyone at some time or another. Of course, there are lots of ways; many plant and fungal poisons target animal-specific proteins; others are stored in inactive forms until release. But a whole host of exquisitely deadly animal toxins have the potential to act against their hosts, and here it may be necessary to invoke co-evolution of resistance. A perfect example of this is found in the pufferfish genera Takifugu and Tetraodon. Their poison, tetrodotoxin (TTX),binds very specifically to the mouth of the voltage-gated sodium channel, the key protein of nerve and muscle that is essential for action potentials and thus the functioning of the nervous system. We know that TTX is fantastically deadly: this is because pufferfish is a prized sushi delicacy in Japan. Chefs licensed to serve fugu need detailed knowledge of fish anatomy, as some parts(particularly the liver and ovaries) are particularly poisonous. This in turn makes `official' fugu sushi so expensive that many Japanese try the do-it-yourself option, resulting in several fatalities per year.Given that the toxicity of TTX is established by human misadventure, and that its target is a very highly conserved protein family, how do pufferfish escape their own poison?Previous work in one species had identified an unusual aromatic amino acid substitution in the first of the four transmembrane domains of a particular sodium channel, Nav1.4, but had not demonstrated that this actually made the protein resistant to the toxin. Byrappa Venkatesh and co-workers from the newly opened Singapore biotech company `Biopolis' took these findings further, with parallel physiological and comparative genetic approaches.The results were simple, but clear; they data-mined the homologous channel genes from the genome projects of related pufferfish representatives of both genera, Takifugu rubiripes and Tetraodon nigroviridis, and compared them with zebrafish and human. Compared with humans, there were two orthologous Nav1.4 channels, consistent with a whole-genome duplication event early in the evolution of ray-finned fishes. If the pufferfish were protected by sodium channel mutations, they were likely to be in one or both of these channels. Again, in both pufferfish species, mutations were found in the highly conserved pore loop of domain I (which forms the entrance to the sodium channel) in both copies of Nav1.4.However, not all changes are functionally significant, so it was necessary to prove that these alterations really did confer resistance to TTX. Accordingly, the corresponding amino acids were altered in a mammalian (rat)channel gene, expressed in cultured cells and their electrophysiological properties compared with the normal channel by whole-cell patch clamp analysis. Whereas sodium current through the rat channel was completely blocked by 1 μmol l–1 TTX, even 100 μmol l–1 TTX achieved only a 55% block of the mutant channels. In fact, altering tyrosine 401 to either cysteine or asparagine (as found in pufferfish) increased the Kd for TTX binding by 2000–2500-fold.So pufferfish sodium channels are resistant to TTX – but why? This is a necessary adaptation, because pufferfish do not make their own TTX but obtain it from microorganisms in their diet, and so must resist ingestion better than humans. The authors outline three intriguing possibilities. Firstly, resistant channels allow pufferfish to eat diets that are toxic to other animals, thus giving them a unique ecological niche. Secondly,accumulating this TTX protects pufferfish from predation. Thirdly, consistent with very high levels of TTX in the ovary, males are actually attracted by very low concentrations of TTX in seawater. So TTX may actually act as a mating pheromone for pufferfish!

Covalent and Noncovalent Interactions for [Metal(dien)nucleobase]2+ Complexes with l-Tryptophan Derivatives: Formation of Palladium−Tryptophan Species by Nucleobase Substitution under Biologically Relevant Conditions

The interaction of the complexes [Pd(dien)(1-MeCyt)]2+ (2) and [Pd(dien)(9-EtGH)]2+ (3) with the amino acids L-tryptophan (Trp) and N-acetyltryptophan (N-AcTrp) was studied and compared with the previously studied platinum analogues [Pt(dien)(1-MeCyt)]2+ (4) and [Pt(dien)(9-EtGH)]2+ (5). Solid-state structures for 2 and 4 are reported. For the palladium complexes, the interaction is pH sensitive. Below pH 5, the noncovalent interaction with stacking between the aromatic amino acid residue and the metalated nucleobase was observed. Fluorescence quenching experiments indicated similar association constants for platinum and palladium derivatives 2-5. Unusual substitution of the model nucleobases 1-methylcytosine (1-MeCyt) and 9-ethylguanine (9-EtGH) by tryptophan was observed in the range of pH 5-11. The resulting species [Pd(dien)(Trp)]+ (6) and [Pd(dien)(N-AcTrp)]+ (7) were characterized using 1H NMR, 13C NMR, and ESI-MS spectroscopy with coordination indicated through the amino and deprotonated amido nitrogens, respectively. Complexes 6 and 7 were also obtained from a solution of [Pd(dien)Cl]+ (1) incubated with either Trp or N-AcTrp, respectively.

Unusual modification methods for the ureido ligand of lanthanocene derivatives

(C5H5)2Ln[OC(PzMe2)=NPh](THF) (Ln = Dy (1a), Er (1b), Yb (1c), Y (1d)) were prepared in good yields by the PhNCO insertion into the Ln-N bond of (C(5)H(5))(2)Ln(PzMe(2))(THF) (PzMe(2) = 3,5-dimethylpyrazolate) in THF at room temperature. Treatment of with p-aminothiophenol in THF at room temperature gives unusual ligand-based substitution derivatives {(C5H5)2Ln[mu-eta1:eta3-OC(p-H2NC6H4S)NPh]}2.2THF (Ln = Dy (2a), Er (2b), Yb (2c), Y (2d)), while reaction of 1c with o-aminothiophenol instead of p-aminothiophenol allows the occurrence of a tandem substitution/cyclization/elimination to form unexpected benzothiazole-2-oxide complex [(C5H5)2Yb(mu-eta1:eta3-OSNC7H4)]2 (3c), representing a novel modification method for non-cyclopentadienyl ligands of lanthanocene derivatives. However, complex does not react with benzyl thiol, indicating that the nature of thiols has a profound influence on the substitution reaction. All complexes were characterized by elemental analysis and spectroscopic properties. The X-ray diffraction analysis reveals that and are solvated monomeric structures, while and are centrosymmetric dimeric ones with an unusual intermolecular hydrogen bond interaction involving THF.

Tithoniaquinone A and Tithoniamide B: A New Anthraquinone and a New Ceramide from Leaves of Tithonia diversifolia

From the leaves of Tithonia diversifolia, four compounds were isolated and identified. Two of them, the anthraquinone tithoniquinone A (1) with an unusual substitution pattern on the anthraquinone skeleton, and the ceramide, named tithoniamide B (2a), are reported for the first time as natural products. Their structures were determined by comprehensive analyses of their 1D and 2D NMR and electron impact (EI) mass spectral data. The remaining two known compounds were identified as psoralen and l-quebrachitol. Preliminary studies showed that tithoniaquinone A (1) is strongly antibacterial and antifungal against Gram-positive Bacillus megaterium and Microbotryum violaceum, respectively, while psoralen has strong algicidal, fungicidal, and antibacterial activities.

Syntheses, Structure, and Bonding of Rb14(Mg1-xInx)30. A Nonstoichiometric Phase with an Unusual Substitution in the Anion Framework

The title compound Rb(14)(Mg(1-x)In(x))(30) (x = 0.79-0.88) has been obtained from high-temperature reactions of the elements in welded Ta tubes. There is no analogous binary compound without Mg. The crystal structure established by single-crystal X-ray diffraction means (space group P2m (No. 189), Z = 1 and a = b = 10.1593(3) Angstroms, c = 17.783(1) Angstroms for x = 0.851) features two distinct types of anionic layers: isolated pentacapped trigonal prismatic In(11)(7-) clusters and condensed [(Mg(x)In(1-x))(5)In(14)](7-) layers. The latter consists of analogous M(11) (M = Mg/In) fragments that share prismatic edges and are interbridged by trigonal M(3) units. The structure shows substantial differences from related A(15)Tl(27) (A = Rb, Cs) in which the cation A that centers a six-membered ring of Tl(11) fragments is replaced by M(3.) Both linear muffin-tin orbital and extended Hückel calculations are used to analyze the observed phase width and site preferences. We further utilize the results to rationalize the distortion of the M(11) fragment in the condensed layer and also to correlate with electrical properties. An isomorphous phase region (Rb(y)K(1-)(y))(14)(Mg(1-x)In(x))(30) (y = 0.52, 0.66 for x = 0.79) is also formed.

Selective Ring-Opening of Nonactivated Amino Aziridines by Thiols and Unusual Nucleophilic Substitution of a Dibenzylamino Group

[Reaction: see text]. The reaction of chiral 2-(1-aminoalkyl)aziridines 1 with different thiols, in the presence of BF3*Et2O, is reported. The obtained products were dependent on the structure of the starting amino aziridines 1. Thus, enantiopure (2S,3S)-2-(alkylthio)alkane-1,3-diamines 2 were obtained from aziridines with C-2 substituents with lower steric congestion and partially racemized (2S,3S)-2,3-bis(alkylthio)alkan-1-amines 3 (ee = 56-66%) from aziridines with larger C-2 subtituents. In both cases, the opening of the nonactivated aziridine ring at C-2 took place with retention of configuration and proceeded with regio- and stereoselectivity at C-2. In the synthesis of 3, 2 equiv of thiol reacts with 1 and the opening of aziridine ring at C-2 was followed by an unusual displacement of the dibenzylamino group by a second equivalent of thiol. The regiochemistry and relative configuration of compounds 3 was established by single-crystal X-ray analysis. A mechanism is proposed to explain the results obtained.

An unusual substitution reaction directed by an intramolecular re-arrangement

Secondary amines and thiols undertake a substitution reaction on the side chain of 2-bromoethyl-pyridinium derivatives ‘directed’ by an intramolecular re-arrangement. Experimental investigations strongly indicate that the reaction is initiated by an alpha addition of the nucleophile onto the iminium moiety of the N-heteroaromatic cation, followed by a cyclisation and an oxidative ring opening. This novel substitution process is able to occur with less reactive nucleophiles that would not undergo conventional substitution with ‘isolated’ bromoethyl moieties.

Solvent‐Mediated Redox Transformations of Ytterbium Bis(indenyl)diazabutadiene Complexes

AbstractThe reactions of diamagnetic [(C9H7)2Yb(THF)2] (2) and [rac‐(CH2‐1‐C9H6)2Yb(THF)2] (3) with tBuN=CH–CH=NtBu (DAD) in toluene result in the formation of the paramagnetic complexes [(C9H7)2Yb(DAD)] (4) and [rac‐(CH2‐1‐C9H6)2Yb(DAD)] (5), respectively. The IR, UV/Vis, and 1H NMR spectroscopic data, the magnetic properties, and the single‐crystal X‐ray diffraction studies of 4 and 5 indicate that in the solid state and in noncoordinating media both complexes are ytterbium(III) derivatives containing the DAD radical‐anion, whereas the 1H NMR and UV/Vis spectra of solutions of 4 and 5 in the coordinating solvent THF give evidence for divalent ytterbium. Recrystallization of 4 and 5 from THF/hexane results in the recovery of the starting ytterbium complexes 2 and 3 due to an unusual redox substitution of the radical anion of diazabutadiene by THF in the coordination sphere of ytterbium. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)