A new biodegradable polydepsipeptide microsphere for application in drug delivery systems

A sequential polydepsipeptide containing a tripeptide sequence L-alanyl-Lalanyl-ethyl L-glutamyl and an-hydroxy acid L-lactic acid, poly(Ala-Ala-Glu(OEt)-Lac), was synthesized to prepare the microspherical particles by the solvent evaporation process. In this case, the solvents play the most important role for the preparation of polydepsipeptide microspheres and, as an example, when 200 mg of the polydepsipeptide dissolved in 10 ml of 98/2% chloroform/dichloroacetic acid mixture was stirred at 400 rpm and 30 C, the microspherical particles with mean diameter of 58m were formed after pouring into 200 ml of 1% (w/v) poly(vinyl alcohol) solution. 17-Estradiol was incorporated into the particles, and the resulting particles were found to contain 5 mg of drug per 25 mg of the particle. The in vivo release of drug from the microspherical formulation was evaluated by measuring the pharmacological influence on rat prostate. It was found that the sufficient amount of drug, keeping the effective pharmacological influence, is supplied during the first 12-week period, followed by an incomplete supplying of drug intil the implant is perfectly degraded in vivo in the 25th week from the start of implantation.     

Highly regio- and stereoselective hydrometallation reactions of fluorine-containing internal alkynes: Novel approaches to fluoroalkylated alkenes

Hydroalumination, hydrocupration, and hydroboration reactions of various fluorine-containing alkynes were investigated. The alkyne reacted smoothly with 2.0 equiv. of Red-Al at −78 °C to give the hydroaluminated adduct in a highly regio- and stereoselective manner, which was treated with iodine, the corresponding vinyliodide being produced in moderate yield. Hydrocupration of the alkynes also took place, but the resulting vinylmetal reacted with various electrophiles sluggishly. In sharp contrast, the reaction with dicyclohexylborane proceeded smoothly to afford the cis-addition products preferentially, which were subjected to Suzuki-Miyaura cross-coupling reaction, leading to trisubstituted alkenes in high yields.     

Dissociation equilibrium between uncharged and charged local anesthetic lidocaine in a surface-adsorbed film

The dissociation equilibrium between uncharged local anesthetic lidocaine (LC) and charged local anesthetic LC (LCH⁺) in a surface-adsorbed film was investigated by measuring the surface tension and pH of aqueous solutions of a mixture of hydrochloric acid and LC. The surface tension values decreased slightly with increasing total molality m_t at 0X₂0.5, where X₂ is the mole fraction of LC in the mixture, while they decreased rapidly with increasing m_t at 0.5<X₂1. It was shown from the pH measurements that almost all LC molecules were changed into LCH⁺ ions by protonation at 0X₂0.5 and both forms coexisted only at 0.5<X₂1. The quantities of the respective LC and LCH⁺ transferred from the aqueous solution to the adsorbed film, i.e., their surface densities, were calculated by applying the thermodynamic equations derived to the surface tension and pH data. A greater quantity of LC than LCH⁺ existed in the adsorbed film at the coexisting composition. The partitioning behavior of LC and LCH⁺ in the adsorbed film was characterized by three composition regions: (1) slight partitioning of low surface-active LCH⁺ in the region at 0X₂0.5, (2) preferential partitioning of LC at 0.5<X₂<around 0.7, and (3) negative partitioning of LCH⁺ at around 0.7X₂1. The present results clearly indicate that uncharged local anesthetics transfer into hydrophobic environments such as cell membranes more than charged ones.     

Asymmetric synthesis of alpha-amino acids: indium-mediated reactions of glyoxylic oxime ether in aqueous media

The indium-mediated allylation and alkylation reactions of the Oppolzer camphorsultam derivative of glyoxylic oxime ether proceeded with excellent diastereoselectivity in aqueous media, providing a variety of enantiomerically pure alpha-amino acids.     

A convenient preparation of 3,3,3-trifluoro-1-propynylamines and their Lewis acid catalyzed reaction with carbonyl compounds leading to (z)-alpha-(trifluoromethyl)-alpha,beta-unsaturated amides

N,N-Dialkyl(3,3,3-trifluoro-1-propynyl)amines were readily prepared by a three-step procedure starting from commercially available 2,2,3,3,3-pentafluoropropanol. These fluorinated alkynylamines reacted smoothly with a variety of aldehydes or ketones in the presence of a catalytic amount of Lewis acid and molecular sieves 4A at ambient temperature to produce the corresponding alpha-(trifluoromethyl)-alpha,beta-unsaturated amides in good to excellent yields with high Z-stereoselectivity.     

An ESR study of NH 3 + , al center and HO2 · radical in alkali feldspars

Paramagnetic centers of NH ₃ ⁺ , Al, and HO₂ · have been observed in alkali feldspars from Aichi prefecture, Japan. The quartet signal has been tentatively ascribed to NH ₃ ⁺ rather than to ·CH₃, although the hyperfine splitting by¹⁴N (I=1) was not observed. The averageg- andA-valuesg _av=2.0033 andA _av ^H =2.45 mT, respectively, were attributed to hydrogen. The powder spectra of Al centers stable up to 400 K were simulated by the anisotropicg factors ofg _zz =2.060,g _xx =2.0014,g _yy=2.0021 andA=0.9 mT. Newly discovered HO₂ · is stable up to 570 K. The intensities of the spectra from NH ₃ ⁺ and Al centers were enhanced by gamma-ray irradiation, while that of HO₂ · was not enhanced. Production efficiency,G-value (radical/100 eV) of NH ₃ ⁺ has been obtained to beG=0.01. These results suggest that ESR dating of feldspars is possible.     

Transformation of indole alkaloids—I : Conversion of oxindole alkaloids into indole alkaloids

Chemical conversion of some natural oxindoles (pteropodine, isopteropodine and isorhynchophylline) into the corresponding indole alkaloids has been made by way of a sequence of reactions which include formation of iminoethers of the natural oxindoles with Meerwein's reagent, reduction of the iminoethers to 2,3-seco-indoles and cyclization of 2,3-seco-indoles to the desired natural indole alkaloids. Sodium borohydride in acetic acid was found to be a specific reagent for the reduction of oxindole-iminoethers to 2,3-seco-indoles which were the key intermediates in these transformations. Yohimbine-oxindole iminoether was similarly converted to yohimbine and pseudoyohimbine. A number of by-products were obtained and their structures were elucidated.