Facile construction and divergent transformation of polycyclic isoxazoles: direct access to polyketide architectures

[reaction: see text] Base-promoted cyclocondensation of C-chloro oximes with cyclic 1,3-diketones affords functionalized isoxazoles in good yield and under convenient reaction conditions. This process enables the synthesis of highly substituted products with notable functional group tolerance. The products obtained are directly converted to a variety of polyketide-derived polycyclic structures including xanthenes, anthracenes, and benzophenones.     

SPECIFIC PHOTOCOUPLING OF 5-BROMOURIDINE TO TRYPTOPHAN IN AQUEOUS FROZEN SOLUTION§

Abstract —5-Bromouridine (BrUd) photochemically reacted with l -tryptophan (trp) only in aqueous frozen solution giving rise to 2-[1,2,3,4-tetrahydro-1-(β-d -ribofuranosyl)-2,4-dioxo-5-pyrimidinyl]-l -tryptophan ( 1a ). Under similar conditions irradiation of 5-bromouracil (BrU) and trp gave the corresponding coupled product 2. Addition of acetone, potassium carbonate or sodium chloride to the frozen system completely inhibited the photocoupling reaction. These photocoupling reactions are suggested to proceed via mixed aggregate formation between trp and BrUd (or BrU) in frozen aqueous solution. Stacking interactions in these aggregates are characterized by an efficient quenching of trp fluorescence by BrUd. Under the same conditions other amino acids such as phenylalanine, tyrosine, histidine and lysine did not react with BrUd, indicating that the photocoupling of BrUd (or BrU) is specific for trp.     

Amidase and peptidase activities of polyclonal immunoglobulin G present in the sera of patients with rheumatoid arthritis

Polyclonal Immunoglobulin (Ig) G from patients with rheumatoid arthritis (RA) and healthy subjects hydrolyzed carbobenzoxy−Val−Gly−Arg p-nitroanilide and D−Pro−Phe−Arg p-nitroanilide. RA IgG exhibited higher activity against the former substrate, but not the latter. On the other hand, RA IgG showed reduced activity against D−Pro−Phe−Arg methylcoumarinamide, when compared with those of the healthy controls. These results suggest that RA IgGs differ from normal IgGs in the substrate specificity of amidase activity. Preliminary studies have shown that two out of three RA IgG samples cleaved a pentapeptide—Gln−Arg−Arg−Arg−Ala−Ala— which is assumed to be associated with the risk of developing RA (Gregersen, P. K. et al. (1987), Arthritis Rheum. 30, 1205–1213). By contrast, virtually no cleavage of the same peptide was observed with IgG from healthy controls. A peptide analog, Gln−Arg−Arg−Trp−Ala, was not cleaved at all by any IgGs examined either from RA patients or healthy controls.     

Mechanism of selective p-quinol formation in the cobalt schiff base complex-catalyzed oxygenation of 4-alkyl-2,6-di-t-butylphenols

The selective formation of $\text{p}$-quinols in the Co(Salpr)-catalyzed oxygenation of 4-alkyl-2,6-di-$\text{t}$-butylphenols in MeOH has been found to involve the rate determining reduction of peroxy-$\text{p}$-quinolato Co(III) complex formed in the initial fast step. An ionic mechanism of the reduction of the OO bond in the peroxy complex by MeOH has been discussed based on kinetic studies. The reactive species in the catalytic cycle is found to be [Co(III)(Salpr)(OH)].     

Improving the properties of the proton exchange membranes by introducing α-methylstyrene in the pre-irradiation induced graft polymerization

New proton exchange membranes (PEMs) were prepared by pre-irradiation induced grafting of α-methylstyrene (AMS)/styrene (STY)/divinylbenzene (DVB) into the crosslinked polytetrafluoroethylene (RX-PTFE) films and successively sulfonated. The new PEMs showed the improved glass transition temperature and chemical stability as compared with the PEMs prepared by pre-irradiation induced grafting of STY/DVB. The balance of the cost, grafting kinetic, thermal properties and the properties of the resulted proton exchange membrane is the key point of this work.     

A new route to 3-alkyl-2,5-di-t-butyl-2,4-cyclopentadienones from 4-alkyl-2,6-di-t-butylphenols

Base-catalyzed reaction of 5-acylmethyl-2,5-di-$\text{t}$-butyl-4-oxa-2-cyclopentenones selectively derived from 4-alkyl-2,6-di-$\text{t}$-butylphenols $\text{via}$ three steps involving oxygenation, acetylation, and acid-treatment gave 3-alkyl-2,5-di-$\text{t}$-butyl-2,4-cyclopentadienones in excellent yield.     

Isolation of new quinidine metabolites and simultaneous determination of quinidine and its metabolites in blood and urine by direct injection HPLC analysis

Summary New quinidine metabolites, including 10,11-dihydrodiol quinidine N-oxide, 10,11-dihydrodiol quinidine and their glucuronides, were found in human urine. A quinidine monitoring HPLC method including these metabolites, is proposed by the direct injection of body fluid samples onto the precolumn for deproteinization followed by reverse phase separation in the analytical column with a column switching technique. The recovery of spiked quinidine and its metabolites in plasma was quantitative (98–102%) with good reproducibility (C.V.: 1.6–4.0%). Several clinical samples such as whole blood and urine were analyzed by the present method.     

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.     

A photochemical synthesis of 3-aryl-1-methylquinolinones

A number of fluorescent 3-aryl-1-methylquinolinones 3 were synthesized by the regiospecific photocoupling reaction of 3-halo-1-methylquinolinones 1 with aromatic and heteroaromatic compounds 2 . An unusual photocoupling product 4 was obtained in the photolysis of 3-iodo-1-methylquinolinone in the presence of benzene. The structure of 4 was unequivocally established by an X-ray crystallographic analysis.     

Stereoselective synthesis of procyanidin B3-3-O-gallate and 3,3″-di-O-gallate, and their abilities as antioxidant and DNA polymerase inhibitor

A simple method for the synthesis of procyanidin B3 substituted with a galloyl group at the 3 and 3″ position is described. Condensation of a benzylated catechin-3-O-gallate electrophile with a nucleophile, catechin and catechin-3-O-gallate, proceeded smoothly and stereoselectively to afford the corresponding dimer gallates, procyanidin B3-3-O-gallate and procyanidin B3-3,3″-di-O-gallate, in good yields. Further, their antioxidant activities on UV-induced lipid peroxide formation, DPPH radical scavenging activity and inhibitory activity of DNA polymerase were also investigated. Among three procyanidin B3 congeners (procyanidin B3, 3-O-gallate and 3,3″-di-O-gallate), the 3,3″-di-O-gallate derivative showed the strongest antioxidant and radical scavenging activity. Interestingly, the 3-O-gallate derivative was the strongest inhibitor of mammalian DNA polymerase with IC₅₀ value of 0.26 μM, although it showed the weakest antioxidant and radical scavenging activity. It became apparent that the presence of a galloyl group at the C-3 position in the proanthocyanidin oligomer was very important for biological activity, however, the antioxidant activity of these compounds was not parallel to the DNA polymerase inhibitory activity.