Structure-activity relationships (SAR) of [D-Arg(2)]dermorphin(1-4) analogues,N(alpha)-amidino-Tyr-D-Arg-Phe-X

In investigating the development of compounds with potent analgesic effects after oral administration, 74 C-terminal analogues (N(alpha)-amidino-Tyr-D-Arg-Phe-X), based on the structure of N(alpha)-amidino-Tyr-D-Arg-Phe-Me beta Ala-OH (ADAMB), were synthesized. Their analgesic activity was evaluated using the mouse-tail pressure test after both subcutaneous and oral administration, and the structure-activity relationships (SAR) were examined in detail. The results clearly indicated that compounds containing beta-amino acid without a side chain at the X position are preferable for expression of potent analgesic activity, and that the free carboxyl group is superior in its analgesic activity to that of the esterified or amidated carboxy group at the C-terminal. In addition, N-methylation of the amide bond at the 4th position contributed to improved analgesic activity. These results indicated that the strong and long-lasting analgesic effect of ADAMB is expressed by the synergistic effects of N(alpha)-amidination, the N-methylation of the amide bond at the 4th position and the carbon chain length (beta-Ala) of the residue at the 4th position, and that this is the most suitable structure.     

NaCl/KCl flux single crystal growth and crystal structure of the new quaternary mixed-metal pnictide: BaCuZn3As3

Synthesis and crystal structure of a new compound, BaCuZn(3)As(3), are reported. Single crystals of BaCuZn(3)As(3) are synthesized via NaCl/KCl flux reaction in a sealed fused silica ampule. Its elemental composition has been determined to be Ba/Cu/Zn/As = 1.03(4):1(0):2.91(6):2.98(3), suggesting BaCuZn(3)As(3) as the chemical formula. The structure of BaCuZn(3)As(3) has been determined by X-ray diffraction. It crystallizes in the orthorhombic Cmcm space group with a = 4.2277(3) A, b = 12.970(1) A, and c = 12.011(1) A at T = 90.7 K, and it exhibits a columnar structure along the a-axis. This structure is isotypic to beta-BaCu(4)S(3) but highly distorted. beta-BaCu(4)S(3) is considered to be a layered structure whereas BaCuZn(3)As(3) is a three-dimensional network.     

Enhanced photodecarboxylation of an aryl ester in polyethylene films

[reaction: see text] Photodecarboxylation is the exclusive photoreaction of 2,4,6-trimethylphenyl (S)-2-methylbutanoate in unstretched high-density polyethylene films. The sole product, (S)-1-(2-methylpropyl)-2,4,6-trimethylbenzene, is formed with complete retention of stereochemistry. In other polyethylene films, organic solvents, and beta-cyclodextrin cavities, cage-escaped products derived from Fries-type bond scission are obtained as well. The results indicate the importance of the media in controlling the conformations of aryl esters and, thereby, their photoreactions.     

In situ observation of the four-step dehydration process of the 1 beta-methylcarbapenem antibiotic CS-834 crystal by X-rays

The 1 beta-methylcarbapenem antibiotic CS-834 takes six crystalline forms depending on ambient conditions. The X-ray powder diffraction revealed that the dihydrate crystal (B2-form) was changed to the monohydrate (B1-form) through the intermediate form (B2'-form). The monohydrate form was then changed to the dehydrate (B0-form) through the intermediate B1'-form. The progress of the dehydration along the needle axis (c-axis) was observed under a microscope. When a single crystal of the B2-form was mounted on a diffractometer and the humidity was reduced, the crystal was gradually changed to the various dehydration forms with retention of the single crystal. The crystals of B2- to B0-forms form isostructures to each other except the solvent water molecules. In the crystal structure of the B1-form, the pivaloyloxymethyl moiety is disordered. One is nearly similar to that of the B2-form, while another is similar to that of the B0-form. Each crystal structure consists of a columnar arrangement of CS-834 along the c-axis, and the water molecules are located between the columns and form a characteristic hydrogen bond network. When the water molecules leave the crystal, the columns slide slightly following the slight conformational change in the pivaloyloxymethyl groups and are connected by another type of hydrogen bond network. Such a rearrangement of the hydrogen bond network should be a motive force of the phase change to the next step due to the dehydration. Since the hydrogen bond network extends along the c-axis, the dehydration proceeds along the c-axis as observed microscopically.     

Physicochemical and crystal structure analyses of the antidiabetic agent troglitazone

The antidiabetic agent troglitazone has two asymmetric carbons located at the chroman ring and the thiazolidine ring and is produced as a mixture of equal amounts of four optical isomers, 2R-5S, 2S-5R, 2R-5R, and 2S-5S. The crystalline powdered drug substance consists of two diastereomer pairs, 2R-5R/2S-5S and 2R-5S/2S-5R. There are many types of crystals obtained from various crystallization conditions. The X-ray structure analysis and the physicochemical analyses of troglitazone were performed. The solvated crystals of the 2R-5R/2S-5S pair were crystallized from several solutions: methanol, ethanol, acetonitrile, and dichloromethane. The ratio of solvent and troglitazone was 1 : 2 (L1/2-form). The monohydrate crystals were obtained from aqueous acetone solution (L1-form). On the other hand, only an anhydrate crystal of the 2R-5S/2S-5R pair was crystallized from various solutions (H0-form). The dihydrous mixed crystal (MA2-form) was obtained from a mixture of the two diastereomer pairs of 2R-5R/2S-5S and 2R-5S/2S-5R in equal amounts by the slow evaporation of aqueous acetone solution. The crystal structure of the MA2-form is similar to the H0-form. When the MA2 crystal was kept under low humidity, it was converted into the dehydrated form (MA0-form) with retention of the single crystal form. The structure of the MA0-form is isomorphous to the H0-form. The MA2-form was converted into the MA0-form and vice versa with retention of the single crystal under low and high humidity, respectively. The crystallization and storage conditions of the drug substances were successfully analyzed.     

Measurement of Cerebral Optical Pathlength as a Function of Oxygenation Using Near-infrared Time-resolved Spectroscopy in a Piglet Model of Hypoxia

Near-infrared spectroscopy (NIRS) has been used for measurement of changes in cerebral hemoglobin concentrations in neonates to study cerebral oxygenation and hemodynamics. In this study, measurements by time-resolved reflectance spectroscopy (TRS) were performed in a piglet model with various degrees of cerebral oxygenation to estimate the differential pathlength factor (DPF). A portable three-wavelength TRS system (TRS-10, Hamamatsu Photonics K.K.) with a probe attached to the head of a piglet was used. Eleven newborn piglets were anesthetized and respired by a ventilator to induce stepwise hypoxia loading. The DPF showed positive linear relationship with arterial hemoglobin (Hb) oxygen saturation and sagittal sinus venous Hb oxygen saturation at 761 and 795 nm. The DPF at 835 nm also showed very slight positive linear relationship with arterial hemoglobin oxygen saturation. The DPF values obtained in this study should contribute to a better understanding of noninvasive measurements by NIRS in neonates.     

Laurepinnacin and isolaurepinnacin,new acetylenic cyclic ethers from the marine red alga laurenciapinnata yamada

The Structure elucidation of the title compounds, two new insecticidal components of the marine red alga $\text{Laurencia}$$\text{pinnata}$ Yamada, is described.     

A facile formation of cyclic selenuranes and a cyclic selenurane oxide in the reaction of 2-methylseleno- and 2-phenylselenobenzoic acids and their derivatives with t-butyl hydroperoxide

The reaction of 2-methylselenobenzoic acid with 1,1′-carbonyldiimidazole followed by addition of t-butyl hydroperoxide gave cyclic selenuranes $\text{2a}$ and $\text{3a}$, suggesting the intramolecular insertion of the neighboring selenium atom into the OO bond of t-butyl 2-methylselenoperoxybenzoate. In the reaction of 2-phenylselenobenzoyl chloride with t-butyl hydroperoxide, cyclic selenurane $\text{2b}$ and the oxide $\text{7}$ were obtained.     

Confirmation of the structures of kuwanons G and H (albanins F and G) by partial synthesis

Conclusive evidence is presented supporting structures $\text{1}$ and $\text{2}$ for two natural Diels-Alder adducts isolated from mulberry and designated as kuwanon G (albanin F, moracenin B) and Kuwanon H (albanin G, Moracenin A).     

Highly stereoselective reduction of α-methylthio and α-phenylthio ketones synthesis of syn- and anti-β-methylthio- and β-phenylthioalcohols

Reduction of α-methylthio and α-phenylthio ketones 1 with L-Selectride gave syn-alcohols 2 in high stereoselectivity except when R¹ was cyclohexyl group, while reduction with Zn(BH₄)₂ gave the isomeric anti-alcohols 3 provided R₃ was methyl group.