Diastereoselective synthesis of new psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type alkene dipeptide isosteres by organocopper reagents and application to conformationally restricted cyclic RGD peptidomimetics

Diastereoselective synthesis of new psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type alkene dipeptide isosteres corresponding to dipeptides having one N-methylamino acid, and application to bioactive peptides, are described. In a key reaction introducing the chiral alpha-alkyl group of the isosteres, organocopper-mediated alkylation of syn-beta-methylated gamma-mesyloxy-alpha,beta-enoate 26a afforded E- and Z-isomers of anti-S(N)2' products in a solvent-dependent manner. The resulting two isosteres, D-Phe-psi[(E)-CH=CMe]-L-Val 27a and D-Phe-psi[(Z)-CH=CMe]-L-Val 28b, which corresponded to trans- and cis-conformers of D-Phe-L-MeVal, respectively, were utilized in a structure-activity relationship study on cyclic RGD peptides 1 and 2, in company with a psi[(E)-CH=CH]-type alkene dipeptide isostere, D-Phe-psi[(E)-CH=CH]-L-Val. The cyclic isostere-containing pseudopeptides 3, 4, and 40 were synthesized and biological activity against integrin alpha(V)beta(3) and alpha(IIb)beta(3) receptors were also evaluated.     

Structurally isomeric two pyridino macrocycles: complexation and structures

Pyridine-based, structurally isomeric two macrocyclic compounds displayed a remarkably different complexation nature. The cage-type compound has an ideal structure for spherical cations, especially for the NH₄⁺ ion, but the reaction with some transition metals and Ln³⁺ produced its protonated species. On the other hand, its isomer formed complexes with alkali metals and lanthanides (1:1) and also with transition metals. Some structures of the complexes were clarified by crystallographic analyses.     

Effects of a nonplanar porphyrin rings on the spin-spin interactions in low-spin ferric porphyrin radical cationst

Low-spin ferric porphyrin radical cations formed by the oxidation of chloro(meso-tetraalkylporphyrinato)iron(III) followed by the addition of bulky 2-methylimidazole show antiferromagnetic coupling, which is interpreted in terms of the interaction between porphyrin a2u and iron d(xy), orbitals caused by the S4 ruffling of the porphyrin core.     

Synthesis,structure, and magnetic properties of dinuclear cobalt(II) complexes with a new phenol-based dinucleating ligand with four hydroxyethyl chelating arms

A new end-off type acyclic ligand with four hydroxyethyl arms, 2,6-bis[bis(2-hydroxyethyl)aminomethyl]-4-methylphenol [H(bhmp)], formed dinuclear cobalt(II) complexes [Co(2)(bhmp)(OAc)(2)]BPh(4) (1) and [Co(2)(bhmp)(OBz)(2)]BPh(4) (2). The complex 1.2.5CH(3)CN (C(50)H(62.5)BCo(2)N(4.5)O(9)) crystallizes in the monoclinic space group C2/c with dimensions a = 25.424(5) A, b = 13.376(2) A, c = 29.913(6) A, beta = 105.930(3) degrees, and V = 9781(3) A(3) and with Z = 8. X-ray diffraction analysis revealed a mu-phenoxo-bis(mu-acetato)dicobalt(II) core structure containing two octahedral cobalt(II) ions. Electronic spectra were investigated for 1 and 2 in the range 400-1800 nm, and the data were typical for the octahedral high-spin cobalt(II) complexes. Magnetic susceptibility was measured for 1 and 2 over the temperature range 4.5-300 K, and the data were analyzed well using our theoretical method. The best fitting parameters were kappa = 0.77, lambda = -116 cm(-1), Delta = 572 cm(-1), and J = -0.44 cm(-1) for complex 1 and kappa = 0.96, lambda = -93 cm(-1), Delta = 616 cm(-1), and J = -0.33 cm(-1) for complex 2.     

Quinoxaline-oligopyrroles: improved pyrrole-based anion receptors

Novel quinoxaline derivatives bearing dipyrromethane or tripyrromethane substituents act as improved anion receptors as compared to the unsubstituted dipyrrolylquinoxaline core from which they are derived.     

Crystal Structure and Property of Perovskite-Type Oxides Containing Ion Vacancy

Studies on the role of oxygen vacancy in structural change of nonstoichiometric perovskites and a property of oxygen-deficient perovskite-related K₂NiF₄ compounds are reviewed.The structural changes on which the authors focused are cation ordering and lattice distortion. The relationship between the distortion and oxygen vacancy was investigated by comparing the structures of Sr₂(Sr_1-xM_x)TaO_6-d (M = Ca²⁺ and Nd³⁺) solid solutions. It was found that distortion of a perovskite-type lattice decreased with an increasing amount of oxygen vacancies. In order to investigate the relationship between the cation ordering on octahedral sites and oxygen vacancy, structures of stoichiometric Sr_2-xLa_xCo_1-yTa_1+yO₆ and oxygen-deficient Sr_2-xLa_xMg_1-yTa_1+yO_6-d solid solutions were compared. The authors' work reveals that the cation ordering affects the amount of oxygen vacancies in addition to cation charge and size.     

Concise total synthesis of flavone C-glycoside having potent anti-inflammatory activity

The total synthesis of anti-inflammatory active flavone C-glycoside isolated from oolong tea extract is achieved. Introducing a C-glucosyl moiety to an aryl system and constructing a fused tetracyclic ring characteristic to this natural product were conducted based on the O-to-C rearrangement of sugar moiety and the successive intramolecular Mitsunobu reaction, respectively. This concise and efficient synthetic pathway is applicable to the large-scale synthesis of target flavone and for constructing a large library of related compounds.     

Solvent control of optical resolution of 2-amino-1-phenylethanol using dehydroabietic acid

The optical resolution of 2-amino-1-phenylethanol (2-APE) by the solvent switch method was investigated using dehydroabietic acid (DAA), a natural chiral acid obtained as one of the main components of disproportionated rosin. The solvent dependency of optical rotation measurements of 2-APE, DAA and the diastereomeric salts suggested solvent control of optical resolution. Both (R)- and (S)-2-APE were resolved, as the first success for aminoalcohols, only by changing the resolving solvents: (S)-2-APE was obtained in high optical purity by a single crystallization operation with polar solvents (epsilon > 50), whereas the efficiency was lower for (R)-2-APE using less polar solvents (20 < epsilon < 40). The results were compared and discussed with reference to the crystal structures of the diastereomeric salts.     

Sensitive analysis of aconitine, hypaconitine, mesaconitine and jesaconitine in human body fluids and Aconitum tubers by LC/ESI-TOF-MS

The Aconitum species (Ranunculaceae) are widely distributed in northern Asia and North America. Their roots are popularly used in herbal medicines in China and Japan. Many cases of accidental, suicidal and homicidal intoxication with this plant have been reported; some of these were fatal because the toxicity of Aconitum is very high. It is thus important to detect and quantify Aconitum alkaloids in body fluids, with high sensitivity. We have developed a simple and sensitive method for measuring four kinds of Aconitum alkaloids (aconitine, hypaconitine, jesaconitine and mesaconitine) by LC/electrospray (ESI)-time-of-flight (TOF)-MS. For all of them, only molecular ions were observed at an orifice voltage of 75 V; at 135 V, base peaks corresponding to [M - 60 + H]+ ions were observed. These four compounds and methyllycaconitine (internal standard) in human plasma samples were purified by solid-phase extraction. The four extracted compounds were completely separated in mass chromatograms; the calibration curves showed good linearity in the range 10-300 ng/ml, and the detection limits were estimated to be 0.2-0.5 ng/ml. Using our method, we also determined the amounts of these compounds in tuber samples. The present method is applicable in clinical and forensic toxicology.