Cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic and benzylic Grignard reagents and their application to tandem radical cyclization/cross-coupling reactions

Details of cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic Grignard reagents are disclosed. A combination of cobalt(II) chloride and 1,2-bis(diphenylphosphino)ethane (DPPE) or 1,3-bis(diphenylphosphino)propane (DPPP) is suitable as a precatalyst and allows secondary and tertiary alkyl halides--as well as primary ones--to be employed as coupling partners for allyl Grignard reagents. The reaction offers a facile synthesis of quaternary carbon centers, which has practically never been possible with palladium, nickel, and copper catalysts. Benzyl, methallyl, and crotyl Grignard reagents can all couple with alkyl halides. The benzylation definitely requires DPPE or DPPP as a ligand. The reaction mechanism should include the generation of an alkyl radical from the parent alkyl halide. The mechanism can be interpreted in terms of a tandem radical cyclization/cross-coupling reaction. In addition, serendipitous tandem radical cyclization/cyclopropanation/carbonyl allylation of 5-alkoxy-6-halo-4-oxa-1-hexene derivatives is also described. The intermediacy of a carbon-centered radical results in the loss of the original stereochemistry of the parent alkyl halides, creating the potential for asymmetric cross-coupling of racemic alkyl halides.     

Liquid chromatographic-mass spectrometric analysis for screening of patients with cystinuria, and identification of cystine stone.

Analyses of amino acids in the urine of a normal human and of patients with heterozygous and homozygous cystinuria have been carried out, using liquid chromatography-mass spectrometry with an atmospheric pressure ionization interface system. A kidney cystine stone was also analysed by this system. Very intense quasi-molecular ions ([M + H]+) of standard cystine, arginine, lysine and ornithine were observed on mass chromatograms as base peaks. Mass chromatograms of the urine samples from a normal human and from patients with heterozygous and homozygous cystinuria were easily distinguishable. The retention times in the mass chromatogram and mass spectrum of kidney stone cystine was almost the same as that of authentic cystine.     

Carbonyl methylenation of easily enolizable ketones

An organometallic reagent prepared from CH₂I₂, Zn, and TiCl₄ is effective for methylenation of the title ketones.     

Determination of Low-Level Ethylenediaminetetraacetic Acid in Water Samples by Ion Chromatography with Ultraviolet Detection

A convenient and sensitive ion chromatographic (IC) method for the analysis of ethylenediaminetetraacetic acid (EDTA) in water samples was proposed. Using a fast reversible reaction of free EDTA and metal–EDTA complexes into Fe(III)–EDTA complex in the presence of Fe(III) ions, sample solutions were applied to an ion-exchange column using a mobile phase (pH 2.3), which was composed of 100 μM Fe(III) chloride and 5 mM methanesulfonic acid. The addition of Fe(III) solution (100 μL) containing 10 mM Fe(III) chloride and 0.5 M methanesulfonic acid to the sample solution (10 mL) permitted the injection of a large volume (400 μL) of sample, which allowed for greater sensitivity. The proposed IC method gave a highly linear (r ² > 0.999) calibration curve ranging 0.005–1.0 μM EDTA and had a limit of detection of 1.5 nM. High repeatability (RSD < 2.1%) and recoveries (88–108%) were also obtained. With this method, total EDTA level in raw and drinking waters were analyzed successfully.     

Studies of Japanese lacquer: Urushiol dimerization by the coupling reaction between urushiol quinone and a triolefinic component of urushiol

Previously, the formation of urushiol quinone from urushiol was demonstrated in the laccase-catalyzed oxidation process of the sap of the Japanese lacquer tree (Rhus vernicifera D.C.) or of lacquer formed from it. This paper presents the results of the investigation on the participation of urushiol quinone in the oxidative polymerization and crosslinking of the sap or the lacquer. The polymeric urushiol was obtained by the fractionation of the mildly oxidized sap (Japanese lacquer), and a specific dimeric urushiol was isolated from it by thin-layer chromatography (TLC). Structural analysis of the dimer illustrated that it has a conjugated triene structure and may be formed by a coupling reaction between urushiol quinone and a triolefinic component of urushiol. Further support for this was given by the spectroscopic study of the reaction between 4-tert-butyl-o-quinone and the triolefinic component of dimethylurushiol, and by the isolation and identification of the coupling product between them.     

Improved separation of alpha chains of collagen type I, type III, and type V by noninterrupted electrophoresis using thioglycolic acid as a negatively charged reducer

Improved separation of alpha chains of collagen type I (alpha 1 [I]2 alpha 2[I]), type III(alpha 1[III]3), and type V (alpha 1[V]alpha 3[V])was achieved by noninterrupted sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a negatively charged reducer, thioglycolic acid. The thioglycolic acid, added to the running buffer of the cathodic reservoir, in the middle of electrophoresis quickly migrated in the gel anode, reducing interchain disulfide linkages in collagen type III and dissociating it into its alpha chain monomer, alpha 1[III], without an interruption of electrophoresis. The alpha chain, alpha 1[III], migrated more slowly than the alpha 1 [I] and alpha 2[I] chains of collagen type I, resulting in an excellent separation of alpha 1[III] from alpha 1[I]. The mobility of alpha 1[III] could be controlled by varying the time of thioglycolic acid addition to the running buffer. This enabled us not only to separate alpha 1[III] from alpha 1[I] and alpha 1[V], but also to precisely quantitate these alpha chains, even at low protein loading of mixed samples.     

Convergent syntheses of polycyclic ethers. Illustrations of the utility of acetal-linked intermediates

One of the most characteristic and spectacular class of compounds isolated from marine sources is the polycyclic ethers. Following the initial report of the structural determination of brevetoxin B, a variety of novel polycyclic ethers have begun to surface. These natural products include ciguatoxins, gambierol, gambieric acids, yessotoxins and gymnocins, each of which exhibit distinct biological properties such as cytotoxicity and neurotoxicity, as well as antiviral and antifungal activities. Because of these intriguing biological activities and their complex molecular architecture, the total synthesis of these compounds has been pursued by many laboratories over two decades. In particular, the development of novel convergent strategies to assemble the structural fragments is crucial for the successful construction of these nano-scale molecules. This Perspective will focus on a recent convergent methodology using an acetal-linkage as a key motif. Application of this methodology culminated in the total syntheses of gambierol and ciguatoxin CTX3C.     

The synthesis of isoquinoline alkaloid and its related compounds using alanine derivatives as chiral auxiliaries

Chiral 1-substituted isoquinoline derivatives, which were obtained by the reaction using alanine derivatives as chiral auxiliaries, were transformed to (S)-2,3,9,10,11-pentamethoxyhomoprotoberberine (7) and a synthetic intermediate for O-methylkreysigine (9) in good yields and high stereoselectivity. The corresponding chiral allyl derivative of isoquinoline was transformed to a pyrrolidinoisoquinoline (16) in a highly enantioselective manner.     

Effect of monomer concentration on characteristics of methacrylic acid-grafted polyethylene film prepared by photografting

The effect of monomer concentration on photografting of methacrylic acid (MAA) onto linear low-density polyethylene (PE) film (thickness=30 μm) was investigated at 60 °C in water solvent together with the location of MAA-grafted chains. Xanthone was used as a photoinitiator which was coated on the film sample earlier. The higher percentage of grafting and graft efficiency were afforded for the system with the higher monomer concentration. The resultant MAA-grafted films were subjected to measurements of pH-responsive character and ability to adsorb cupric ion in order to understand the characteristics of function introduced. The grafted samples exhibited the pH-responsive character, where they shrank and swelled in acidic and alkaline media, respectively. The pH-responsive character of the grafted films was higher for the samples prepared in the system with a higher monomer concentration. Moreover, the grafted samples exhibited the ability to adsorb cupric ion, and the ability was reduced when the sample was prepared in the system with a higher monomer concentration. The different extents of the pH-responsive character and ability to adsorb cupric ion of the resulting grafted PE films were discussed in terms of location of grafted chains in the film substrate, which was determined by a scanning electron microscope and an attenuated total reflection infrared spectroscopy.     

Studies on palytoxins

The complete structure of palytoxin (1) was elucidated by us in 1982.¹ Our continuous interests in palytoxin led us to examine minor constituents of Okinawan Palythoa tuberculosa. In this paper, we describe successful isolation and structural elucidation of four minor toxins, which were named homopalytoxin (2), bishomopalytoxin (3), neopalytoxin (4) and deoxypalytoxin (5).