Search

N-allylic carboxamides and lactams undergo mild and highly chemoselective alpha-iodination reactions to produce adequate yields of alpha-iodo amides and lactams. The synthesis involves reacting N-allylic amides and lactams with I2 and 2,6-lutidine at room temperature. The iodides formed in the reactions were converted to beta lactam or bicyclic lactam derivatives with high stereoselectivity by a nucleophilic substitution or a radical iodine atom-transfer reaction.

Reaction between (Rh(2)(OAc)(4)) and various ligands yields (Rh(2)(OAc(4) (L)(2))). The ligands are slightly different in nature and have different substituents adjacent to the donor nitrogen. These reactions are performed to analyze the influence of intraligand interactions on site-specific metal bonding. Hydrogen bonding of the exocyclic substituents is vital in determining the metal bonding.

Introduction Flavonoids are converted to inactive metabolites like glucuronides in the gut, and circulate mainly as glucuronides in blood stream, resulting in low concentrations of active aglycones in plasma. It is therefore unclear how oral flavonoids exert their effects in tissues. We recently reported the plasma pharmacokinetics of some flavonoids and suggested the possibility that the absorbed flavonoids modified macrophage functions leading to enhance bacterial clearance. We aimed to confirm their pharmacological profiles focusing on tissue macrophages. Methods Pseudoinfection was induced by intradermal injection of FITC-conjugated and killed Staphylococcus aureus into the ears of mice treated with or without genistein 7- O-glucuronide (GEN7G, 1 mg/kg, i.v.). FACS analysis was performed on single cell suspensions dispersed enzymatically from the skin lesions at 6 h post pseudoinfection to evaluate phagocytic activities of monocytes/macrophages (CD11b+Ly6G−) and neutrophils (CD11b+Ly6G+). Phagocytosis of the FITC-conjugated bacteria by four glucuronides including GEN7G was evaluated in cultures of mouse macrophages. Results After GEN7G injection, genistein was identified in the inflamed ears as well as GEN7G, and the phagocytic activity of CD11b+Ly6G− cells was increased. GEN7G was converted to genistein by incubation with macrophage-related β-glucuronidase. Macrophage culture assays revealed that GEN7G increased phagocytosis, and the action was dampened by a β-glucuronidase inhibitor. Binding of aglycones to estrogen receptors (ERs), putative receptors of flavonoid aglycones, correlated to biological activities, and glucuronidation reduced the binding to ERs. An ER antagonist suppressed the increase of macrophage function by GEN7G, whereas estradiol enhanced phagocytosis as well. Conclusions This study suggests a molecular mechanism by which oral flavonoids are carried as glucuronides and activated to aglycones by β-glucuronidase in tissue macrophages, and contributes to the pharmacological study of glucuronides. [ABSTRACT FROM AUTHOR]

Background: Rikkunshito, a traditional Japanese (Kampo) medicine, has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux. This study investigated the exposure and pharmacokinetics of the ingredients of rikkunshito in healthy volunteers. Methods and Results: First, an exploratory nonrandomized, open-label, one-period, noncrossover study using four healthy Japanese volunteers to detect 32 typical ingredients of rikkunshito in plasma and urine. As a result, 18 or 21 of 32 ingredients was detected in plasma or urine samples after oral administration of rikkunshito (7.5 g/day). Furthermore, a randomized, open-label, three-arm, three-period, crossover study using 21 subjects was conducted to determine the amounts of exposure and pharmacokinetic parameters of nine ingredients derived from rikkunshito (atractylodin, atractylodin carboxylic acid, pachymic acid, 3,3′,4′,5,6,7,8-heptamethoxyflavone, naringenin, nobiletin, liquiritigenin, isoliquiritigenin, and 18β-glycyrrhetinic acid) after oral administration of rikkunshito at three different doses (2.5, 5.0, or 7.5 g/day) during each period. The pharmacokinetic profiles of the nine ingredients in plasma were characterized. The geometric means (95% confidence interval) for the Cmax of the ingredients at a dose of 7.5 g were 1570 (1210–2040), 14,300 (12,200–16,800), 91.0 (71.8–115), 105 (75.6–144), 1150 (802–1650), 35.9 (24.6–52.5), 800 (672–952), 42.8 (30.4–60.3), and 55,600 (39,600–78,100) pg/mL, respectively, and for the AUC0–last were 1760 (1290–2390), 12700 (11,100–14,600), 1210 (882–1650), 225 (157–322), 4630 (2930–7320), 35.7 (20.4–62.7), 4040 (3260–5010), 122 (88.2–168), and 832,000 (628,000–1,100,000) pg·h/mL respectively. Conclusions: We identified the ingredients of rikkunshito that are absorbed in humans. Furthermore, we determined the pharmacokinetics of nine ingredients derived from rikkunshito. This information will be useful for elucidating the pharmacological effects of rikkunshito. Trial Registration: Japan Pharmaceutical Information Center [ABSTRACT FROM AUTHOR]

Abstract: We focused on the iron-complexes of sanshools (hydroxyl-α-sanshool, hydroxyl-β-sanshool, and γ-sanshool) as the key intermediates for the selective synthesis of these structurally unstable compounds. Consequently, we developed a concise and selective method for the total synthesis of sanshools in 5–6 steps (26–45% overall yield), including complexation of dienes with iron tricarbonyl group. [Copyright &y& Elsevier]

Bis(oxazolinyl)phenylrhodium(III) aqua complexes, (Phebox)RhX2(H2O) [X = Cl, Br], were found to be efficient Lewis acid catalysts for the enantioselective addition of allyl- and methallyltributyltin reagents to amino aldehydes. The reactions proceed smoothly in the presence of 5-10 mol % of (Phebox)RhX2(H2O) complex at ambient temperature to give the corresponding amino alcohols with modest to good enantioselectivity (up to 94% ee). [ABSTRACT FROM AUTHOR]

Two new ligands, N1, N2-Bis(3-phenylallylidene)propane1,2-diamine, ca2men and 1, 2-diphenyl-N, N'-bis(3-phenylallylidene) ethane1, 2-diamine, phca2dpen, and their corresponding copper(I) complexes, [Cu(ca2men)2]BPh4 1 and [Cu(phca2dpen)2]ClO4 2, were synthesized and characterized by C,H,N analyses, IR, and UV/VIS spectroscopy. The crystal and molecular structures of 1 and 2 were determined by X-ray crystallography from single-crystal data. The coordination polyhedron about the CuI center in the two complexes is best described as a distorted tetrahedron. The spectral analysis of the complexes identifies an increasing in wavelength of the first metal to ligand charge transfer band with increasing of the substituents in the ligands. A quasireversible redox behavior is observed for complex 1 and 2 (E1/2= 0.71 and 0.83 V). [ABSTRACT FROM AUTHOR]

The reaction of VO(ph-acac)2 (ph-acac=phenyacetylacetonato) with NaHB(pz)3 (pz=pyrazole) or NaHB(3,5-Me2pz)3 in the solution of MeOH gave oxovanadium (IV) complexes HB(pz)3VO(ph-acac) · 2H2O (1) and HB(3,5-Me2pz)3VO(ph-acac) · 2H2O (2), respectively. An oxovanadium complex, V2O4[HB(pz)3]2 · 2CH3CN (3), was obtained by the reaction of VOSO4 · 3H2O with tri(pyrazolyl)borate sodium in MeOH. The complexes 1, 2 and 3 were characterized by elemental analysis, IR, UV-Vis, NMR. In particular, the crystals of complex 1 and 3 were determined by X-ray diffraction. They crystallize in space group P21/c, a=16.497(5) Å, b=7.6601(19) Å, c=17.199(4) Å, β=107.498(19)°, V=2072.8(9) Å3, Z=4, R=0.0371 (I>2σ(I)) for 1; in the monoclinic, space group Pbca, with cell dimensions of a=15.531(2) Å; b=18.007(2) Å; c=10.725(2) Å; V=2999.4(8) Å3, Z=4, R= 0.0401(I>2σ(I)) for 3. Structure analyses have shown that complex 1 is a monomeric oxovanadium complexe containing polypyrazolylborate and two lattice water. Complex 3 consists of a V2O4(HB(pz)3)2 molecule and two free CH3CN lattice molecules in an unit cell. Both possess a similar coordination mode for the vanadium atom. In addition, luminescence properties and thermal analysis characterization of the complexes also are discussed. [ABSTRACT FROM AUTHOR]

Three silver(I) complexes, [Ag(ca2en)(PPh3)]ClO4 (1), [Ag(ca2en)(PPh3)2]ClO4 (2) and [Ag(ca2en)2]ClO4 (3), where ca2en = N,N′-bis(trans-cinnamaldehyde)ethylenediimine, have been synthesized and characterized spectroscopically. The crystal structure of (1) was determined by X-ray diffraction methods. Crystal data for 1: C38H35AgClN2O4P, triclinic, P1, a = 12.086(2), b = 18.204(2), c = 8.550(2) Å, α = 102.69(1), β = 105.85(1), γ = 91.47(1)°, V = 1758.0(5) Å3, Z = 2, R(F) = 0.070, wR (F) = 0.064, T = 296 K. The coordination geometry of the Ag atom is distorted trigonal involving two N atoms of ca2en and one P atom of triphenylphosphine (PPh3). [ABSTRACT FROM AUTHOR]

Mn(II) complexes Mn[HB(pz)3]2 (1) (pz = pyrazole) and Mn[HB(3,5-Me2-pz)3]2 (2) have been obtained by the reaction of Mn(OOCCH3)2 with NaHB(pz)3 and NaHB(3,5-Me2-pz)3 in MeOH, respectively. The two complexes (1) and (2) were characterized by IR, elemental analyses, and x-ray diffraction. Complex (1) crystallizes in the space group C2/c, a = 18.971(3) Å, b = 13.700(3) Å, c = 19.056(3) Å, β = 111.378(10), V = 4612.0(13) Å3, Z = 2. Complex (2) crystallizes in the space group R-3, a = 10.9832(18) Å, b = 10.983(2) Å, c = 24.785(3) Å, γ = 120°, V = 2589.3(7) Å3, Z = 3. X-ray structure analysis has shown that the complexes (1) and (2) all are monomeric neutral complexes, and possess similar coordination modes around the metal Mn centers. In addition, some related bonding distances, angles, and structural properties are discussed. [ABSTRACT FROM AUTHOR]

V(IV)O(H 2 O) 2 (2,6-pyridinedicarboxylate)·2H 2 O ( 1 ) was obtained by the reaction of VO(acac) 2 with 2,6-pyridine dicarboxylic acid in MeOH and water. Complex ( 1 ) was characterized by IR spectroscopy, element analysis and X-ray diffraction. It crystallizes in space group P . X-ray structure analysis has shown that complex ( 1 ) is a monomeric neutral complex containing vanadyl ion, 2,6-pyridinedicarboxylate ligand and coordinated water, possessing distorted octahedral geometry. Complex ( 1 ) is constructed from mononuclear vanadium, V(IV)O(H 2 O) 2 (2,6-pyridinedicarboxylate) units and crystallization water molecules held together in an extensive two-dimensional network via O-H···O hydrogen bonds, π-π stacking interactions between parallel aromatic pyridines, and face-to-face stacking interactions between parallel carbonyl groups of 2,6-pyridine dicarboxylic acid ligands along the plane formed by the x , z axis of the unit cell. [ABSTRACT FROM AUTHOR]

The V(V) complex VO2(acac)(1,10-phen) (1) has been obtained by the reaction of VO(acac)2 with 1,10-phenanthroline. The complex (1) was characterized by IR, elemental analyses and X-ray diffraction studies which reveal that it crystallizes in the space group P21/c, a = 8.052(4) Å, b = 16.140(6) Å, c = 12.153(4) Å, β = 90.69(15)°, V = 1579.2(11) Å3, Z = 4. It is a monomeric neutral oxovanadium(V) complex containing 1,10-phenaroline and acac as mixed ligands and possessing a disordered octahedron geometry around the vanadium atom. [ABSTRACT FROM AUTHOR]

Reports that [M(saccharinato)2(H2O)4] (M = Cu2+, Ni2+, Co2+) react with nicotinamide to form mixed ligand complexes. Determination of crystal structures by x-ray diffraction; Octahedral configuration coordinated by two monodentate saccharinato ligands in the trans arrangement through the deprotonated ring nitrogens.

The reaction of [Rh2(OAc)4] with adenine, 9-methyladenine, 9-ethylguanine, adenosine, guanosine, deoxyguanosine, or inosine in methanolic aqueous solution at room temperature gave specifically and quantitatively pink complexes of adenine or its derivatives (=L), [Rh2(OAc)4(L)] (the dirhodium-core:L ratio of 1:1). The reaction of [Rh2(HNOCCF3)4] or [Rh2(OAc)2(HNOCCF3)2] with these nucleobases or nucleosides (=L) gave non-specifically pink or red complexes with dirhodium-core:L=1:1 for adenine derivatives while 1:2 for guanine derivatives. Recrystallization of a 9-methyladenine adduct from a nitric acid solution yielded [Rh2(OAc)2(HNOCCF3)2(9-methyladeninium)2]·(NO3)2 (1), whose crystal structure was determined by X-ray diffraction, showing that two N(1)-protonated 9-methyladeninium molecules coordinate to both the axial-positions of a [Rh2(OAc)2(HNOCCF3)2] nucleus through N(7) with the formation of an intramolecular interligand N(6)&z.sbnd;H⋯O(acetato) hydrogen bond. Crystal structures of guanine derivatives, [Rh2(OAc)2(HNOCCF3)2(9-ethylguanine)2]·2MeOH·2H2O (2), [Rh2(HNOCCF3)4(L)2]·3H2O (L=guanosine (3), deoxyguanosine (4), or inosine (5)), and [Rh2(OAc)2(HNOCCF3)2(guanosine)2]·3H2O (6) were determined, showing that the dirhodium core is occupied at either axial-side by two guanine or hypoxanthine moieties through N(7) with the formation of an intramolecular interligand N(amidato)&z.sbnd;H⋯O(6) hydrogen bond. Each of guanosine molecules in 3, 4, and 6 or inosine molecules in 5 adopts the syn, gauche–gauche (or gauche–trans for one molecule in 3), and C(2′)-endo (or C(2′)-endo-C(3′)-exo for one molecule in 4) conformations to form an intramolecular O(5′)&z.sbnd;H⋯N(3) hydrogen bond. The formation of interligand N(6)&z.sbnd;H⋯O hydrogen-bonding associated with the sterically constrained octahedral coordination geometry about the rhodium atom bonded to N(7), as observed in 1, and/or to N(1) of adenine may give a structural basis for the adenine-specific reactivity of [Rh2(OOCR)4], where the carboxylato ligand could function as hydrogen-bonding acceptor only. Similarly, the formation of interligand N&z.sbnd;H⋯O(6) hydrogen-bonding observed in 2–6 suggests that [Rh2(HNHNCR)4] could function as guanine-specific reagents, where the amidinato ligand could function as hydrogen-bonding donor only. The interligand steric constraint due to the octahedral coordination geometry may also explain no reactivity of [Rh2(OOCR)4] toward native B-DNA (right-handed double-stranded structure) but specific bonding to single-stranded and possibly to left-handed double-stranded structures. [Copyright &y& Elsevier]

An investigation into the interactions between thiamine monophosphate (TMP) and anions has resulted in the preparation and X-ray characterization of the compounds (TMP)(Hg2Br5)·0.5H2O (1) and (TMP)2(Hg3I8) (2). In each compound the TMP molecule exists as a monovalent cation in the usual F conformation. The halogenomercurate anions occur in two-dimensional (2-D) network in 1 or one-dimensional (1-D) chain in 2. In both 1 and 2, the structures consist of alternating cationic sheets of the hydrogen-bonded TMP molecules and anionic sheets of the polymeric halogenomercurate anions. The TMP molecule binds to the polymeric anions through the characteristic ‘anion bridge I’, C(2)&z.sbnd;H⋯X⋯pyrimidinium (X=Br in 1 and I in 2), and electrostatic interactions between electropositive S(1) and halogen atoms. The ‘anion bridge II’ of the type N(4′1)&z.sbnd;H⋯X⋯thiazolium (X=phosphate group) plays a role in stabilizing the molecular conformation. The biological implication of the host–guest-like complexation between TMP and polymeric anions is discussed. [Copyright &y& Elsevier]