A new method for the high performance liquid chromatographic determination of TA-870, a dopamine prodrug (catechol ester compound)

A new method for the high performance liquid chromatographic (HPLC) determination of N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine (TA-870), a dopamine prodrug, in biological fluid has been developed. In order to measure with an electrochemical detector (ECD), TA-870 was passed first through an immobilized carboxylesterase column to be converted to the electrochemically active deethoxycarbonylated TA-870 (DEC-TA-870). The properties of this carboxylesterase immobilized on Sepharose 4B were examined by this flow injection system. Hydrolysis of TA-870 with this immobilized carboxylesterase was a maximum at pH 7-8 and 50 degrees C, and the activity decreased in the presence of organic solvent such as acetonitrile. For the determination of TA-870 in biological fluids, an HPLC-immobilized enzyme-ECD system using a column-switching technique was developed. The blood was deproteinized with ethanol, and TA-870 in the ethanol extracts was adsorbed in Bond Elut C18. The dichloromethane eluate from Bond Elut C18 was injected into the HPLC system. The HPLC apparatus was composed of three pumps, two separation columns (LiChrosorb Si 60 and mu Bondasphere), a trap column (Bond Elut), an enzyme column, ECD and the column-switching system. The calibration curve for TA-870 in blood was linear in the range from 2 to 200 ng/mL. This new assay method might be useful also for the determination of other catechol ester compounds.     

Oxidative degradation of poly(isophthaloylhydrazine‐1,2‐diyl)s

The condensation polymerization of isophthalodihydrazide and diphenyl isophthalate affords poly(isophthaloylhydrazine‐1,2‐diyl). High‐molecular‐weight poly(5‐tert‐butylisophthaloylhydrazine‐1,2‐diyl) is prepared by the polycondensation of 5‐tert‐butylisophthalodihydrazide and bis(4‐nitrophenyl) 5‐tert‐butylisophthalate in NMP at 100 °C. T_d of the poly(diacylhydrazine) is observed above 300 °C. No T_g is observed below T_d. The high‐molecular‐weight poly(diacylhydrazine) exhibits a film‐forming ability. The poly(diacylhydrazine) decomposes on treatment with an oxidant such as sodium hypochlorite solution to obtain the corresponding carboxylic acid and nitrogen. However, poly(diacylhydrazine) was stable to oxygen and hydrogen peroxide even in the presence of transition metal ions. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6255–6262, 2008     

Allylation of methylenecyclopropanes with allylindium reagents

Methylenecyclopropanes carrying a hydroxymethyl group at the ring underwent stereoselective allylindation with allylindium sesquiiodide to afford the allylated products, in which the allyl group was delivered at the external sp² carbon via cyclopropylindium intermediates. The reaction of ethyl 2-cyclopropylideneacetate and triallylindium afforded the 1,4-adduct along with dimeric products.     

Living cationic polymerization of 2‐adamantyl vinyl ether

Living cationic polymerization of 2‐adamantyl vinyl ether (2‐vinyloxytricyclo[3.3.1.1]^3,7decane; 2‐AdVE) was achieved with the CH₃CH(OiBu)OCOCH₃/ethylaluminum sesquichloride/ethyl acetate [CH₃CH(OiBu)OCOCH₃/Et_1.5AlCl_1.5/CH₃COOEt] initiating system in toluene at 0 °C. The number‐average molecular weights (M_n's) of the obtained poly(2‐AdVE)s increased in direct proportion to monomer conversion and produced the polymers with narrow molecular weight distributions (MWDs) (M_w/M_n = ～1.1). When a second monomer feed was added to the almost polymerized reaction mixture, the added monomer was completely consumed and the M_n's of the polymers showed a direct increase against conversion of the added monomer. Block and statistical copolymerization of 2‐AdVE with n‐butyl vinyl ether (CH₂?CH? O? CH₂ CH₂CH₂CH₃; NBVE) were possible via living process based on the same initiating system to give the corresponding copolymers with narrow MWDs. Grass transition temperature (T_g) and thermal decomposition temperature (T_d) of the poly(2‐AdVE) (e.g., M_n = 22,000, M_w/M_n = 1.17) were 178 and 323 °C, respectively. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1629–1637, 2008     

Enantioselective preparation of C-ring fragment of cotylenin A via catalytic asymmetric intramolecular cyclopropanation of α-diazo β-keto ester

A synthetic pathway to the C-ring fragment of cotylenin A which emerged from our retrosynthetic analysis of cotylenin A is described. The catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of the α-diazo-β-keto ester bearing 2,4,6-trimethylphenyl group as the ester part has been found to afford the crystalline product with high ee, which allowed to establish the approach to the C-ring fragment which required ten-pot operations. The developed approach would be beneficial to a large scale synthesis of the C-ring fragment for the total synthesis of cotylenin A.     

Enantioselective total synthesis of sacrolide A

An enantioselective total synthesis of sacrolide A, an antimicrobial and cytotoxic fourteen-membered macrolactonic oxylipin isolated from an edible freshwater cyanobacterium, has been accomplished from a known carboxylic acid in 20% overall yield by a concise ten-step sequence. The key transformations include chiral oxazolidinone-based diastereoselective installation of two hydroxy-bearing stereocenters, the Horner–Wadsworth–Emmons olefination to construct the full carbon skeleton, and the Shiina macrolactonization to establish the fourteen-membered macrolide structure.     

Test of athermal terms of activity coefficient models by Monte Carlo simulation with hard-core models

The infinite dilution activity coefficients of exactly athermal fluids were calculated by Monte Carlo simulation with hard-core models. The hard-core models used in this work were hard-sphere and hard-spherocylinder models. The Widom test particle method was adopted to calculate the residual chemical potentials of solutes in pure solvent and in pure solute solutions. The infinite dilution activity coefficients of solutes were obtained from the residual chemical potentials of solutes. The infinite dilution activity coefficients calculated by Monte Carlo simulation were compared with those of athermal terms in activity coefficient equations. Staverman–Guggenheim equation overestimates the activity coefficients. The deviations of activity coefficients increase with increasing the hard-core volume of solute. Flory–Huggins equation based on molar volume gives good results for the hard-spherocylinder systems. Elbro-FV equation gives good results for both the hard-sphere and hard-spherocylinder systems.     

Orientation Control of Photo‐Immobilized Antibodies on the Surface of Azobenzene‐Containing Polymers by the Introduction of Functional Groups

In our photo‐induced immobilization technique for an antibody (IgG) using azopolymers, the introduction of COOH and NMe₂ into the azopolymers, which can introduce surface charges, strongly affected the immobilization properties such as the efficiency of immobilization and the activity of the immobilized IgG (i.e., the orientation of the immobilized IgG). The introduction of COOH promoted a more active orientation of the immobilized IgG. The orientation was determined during the adsorption process onto the azopolymer surface in solution before photo‐immobilization, and was maintained during the photo‐immobilization. The surface charge of the azopolymer appears to be an important factor for IgG orientation, which involves electrostatic interactions between its Fab and the azopolymer surface.