Conformational effects on lipase-mediated acylations of 2-substituted cyclohexanols

Lipase-mediated acetylations of trans- and cis-2-substituted cyclohexanols gave the corresponding (1R)-cyclohexyl acetates and (1S)-cyclohexanols in high yields and ee, but c-4-tert-butyl-c-2-ethenyl-r-1-cyclohexanol was unreactive owing to the steric interaction between the axial OH group and the axial H atoms at the 3- and 5-positions. In the cis-isomer the OH group occupies an equatorial position to bind to the lipase, and less bulky axial alkenyl and alkynyl groups might not so much prevent acetylations than an alkyl group.     

Synthesis of Urea‐Tethered Disaccharides in Water

A new method for the synthesis of urea‐linked disaccharides in aqueous media has been developed. The key feature of our approach is two strained Steyermark‐type gluco‐ and galactopyranosyl oxazolidinones. Each oxazolidinone is attached to a pyranose ring in a di‐equatorial trans‐annulation framework. Reaction of these oxazolidinones with 4‐aminohexopyranose in water proceeded smoothly to afford the urea‐tethered cellobiose and lactose analogues. The galactose‐type oxazolidinone proved to be more reactive than the glucose‐type, which is explained by the presence of an axial hydroxy group at C4 in the former.     

Comparison of the reactivity of ammonium halides using hydrogen-isotope exchange reaction in a gas-solid system

In order to reveal the behavior of the hydrogen atoms in an ammonium salt, the hydrogen-isotope exchange reaction between each of the three ammonium halides and tritiated water vapor was followed at 50–80°C. Analyzing the data obtained by theA-McKay plot method, the following has been quantitatively clarified: both the reactivity of an ammonium halide and the temperature dependence of its reactivity increase when the electronegativity of the halogen element in the ammonium halide is larger.     

Method of kinetic analysis of photodegradation: nifedipine in solutions

A rate equation for photodegradation was derived from Lambert-Beer's law and Grotthus-Draper's law: -dc/dt=k1(1-exp(-(k2c+k3(c0-c))))k2c/(k2c+k3(c0-c)) where c is the concentration of reactant, c0 is the initial concentration of reactant, t is time, k1 is the rate constant, and k2 and k3 are the absorption coefficient of reactant and its photodegradation product, respectively. In a case where the photodegradation products have no photoabsorption, k3 assumes the value of zero in the above general equation. In a case where the photodegradation products have the same spectrum and molar absorptivity as that of the reactant, k3 assumes the value of k2, and hence the photodegradation is not a first-order reaction; however, the equation itself gives the pseudo-first-order reaction rate equation. In a case where the concentration of reactant is high enough, the equation approaches a zero-order reaction rate equation. The photodegradation rate of nifedipine in solutions under a germicidal lamp, near an ultraviolet fluorescent lamp and a fluorescent lamp was analyzed using the above equation. The photodegradation rate was directly proportional to the amount of light absorbed, and fitted well with the equation. The above theoretical equation was substantiated by the photodegradation of nifedipine, and hence is expected to apply to other photosensitive drugs.     

Analysis of the reactivity of materials having two different kinds of functional groups using the A″-McKay plot method

The hydrogen-isotope exchange reaction between HTO vapor (as a gaseous material) andp-aminophenol (or -alanine) (as a solid material) having two different kinds of functional groups, has been studied to reveal the reactivity of the compounds. The reaction has been analyzed by the A-McKay plot method and the rate constants (k) for each group have been obtained. Comparison ofk leads to the following: (1) the effect of the NH₂ group inp-aminophenol on the reactivity is greater than that in -alanine, and (2) the reactivity of compounds having two different kinds of functional groups can be analyzed by the A-McKay plot method only.     

Estimation of electrophoretic mobilities of red blood cells in 1-G and microgravity using a miniature capillary electrophoresis unit

Electrophoretic mobilities of red blood cells (RBCs) were measured in microgravity using a home-made capillary electrophoresis unit, which consisted of two small reservoirs of 0.6 mL and a fused-silica capillary tubing with 2 cm in length and 50 num in inner diameter. Migration of RBCs was observed by a microscope at 1000 times magnification and recorded on a videotape. The experiments were performed during stays in microgravity (about 0.01 G), which lasted 20 s and were attained by parabolic flights of an aircraft. On average, the electrophoretic mobilities of RBCs determined in microgravity were about 30% higher than those measured at 1-G condition irrespectively whether the cells were suspended in saline or serum during measurements. This difference might be explained as being mainly due to the cell floating in microgravity. Morphological changes of RBCs may contribute partly to the difference, while the variation in viscosity of the medium under microgravity could play only a minor role.     

NMR Spectroscopic Observation of a Metal‐Free Acetylide Anion

A metal‐free acetylide was observed by using NMR spectroscopy. Metal‐free acetylides are closely related to reactive intermediates (carbanions) in solution; therefore, they have been regarded as unobservable species. However, we generated this highly reactive and unstable species through the deprotonation of phenylacetylene by using the strong nonmetallic phosphazene base tBu‐P4. In the presence of tBu‐P4, the J coupling between the ethynyl carbon and hydrogen nuclei (¹J_C,H) of phenylacetylene disappeared; this indicates the deprotonation of the alkyne terminal. Furthermore, a large low‐field shift (approximately 90 ppm) of the alkyne carbon resonance was observed. We concluded that we have observed a metal‐free carbanion with a formal charge on an sp‐hybridized carbon atom for the first time.     

Intramolecular 1,3‐Dipolar Cycloaddition‐Mediated Stereoselective Synthesis of Disubstituted Cyclopentane: A Simple Model for the Cyclopentane Ring System of Polycyclic Oroidine Alkaloids

We present a diastereoselective synthesis of disubstituted cyclopentane 8 having a nitrogen‐containing quaternary carbon center, which is found in axinellamine A ( 5 ) and related compounds. During this work, we found that the 1,3‐dipolar cycloaddition product 24 immediately underwent intramolecular redox reaction at the newly formed morpholin‐2‐one moiety, thus affording disubstituted cyclopentane containing a tertiary amine ( 9 ) stereoselectively in good yield. The amine 9 was successfully converted into guanidine 31 , which corresponds to 8 , through iminium cation–enamine isomerization.     

α-Trifluoromethyl Chalcones as Potent Anticancer Agents for Androgen Receptor-Independent Prostate Cancer

α-Trifluoromethyl chalcones were prepared and evaluated for their antiproliferative activities against androgen-independent prostate cancer cell lines as well as five additional types of human tumor cell lines. The most potent chalcone 5 showed superior antitumor activity in vivo with both oral and intraperitoneal administration at 3 mg/kg. Cell-based mechanism of action studies demonstrated that 5 induced cell accumulation at sub-G1 and G2/M phases without interfering with microtubule polymerization. Furthermore, several cancer cell growth-related proteins were identified by using chalcone 5 as a bait for the affinity purification of binding proteins.