A GaCl3-catalyzed reaction of alpha,beta-unsaturated ketones with isocyanides leading to the formation of unsaturated lactone derivatives is described. This is the first example of the catalytic [4+1] cycloaddition of alpha,beta-unsaturated ketones and isocyanides. GaCl3 is an excellent catalyst due to its lower oxophilicity, which is desirable for all of the key steps, such as E/Z isomerization, cyclization, and deattachment from the products.
Hepatitis viruses and alcohol are major causes of liver disease. This study was aimed at investigating the effect of alcohol intake on the replication of hepatitis C virus and the efficacy of interferon therapy. Fifty-three patients who were histologically proved to have chronic hepatitis C were tested. Of these, 16 were diagnosed as habitual drinkers whose cumulative total consumption of alcohol was more than 100 kg or who had consumed at least 60 gm of ethanol daily for at least 5 yr. The quantities of hepatitis C virus RNA in serum were measured with a competitive assay that combined reverse transcription and polymerase chain reaction. The subjects received a 26-wk course of interferon-alpha therapy. There were no significant differences in age and ALT levels between habitual drinkers and nonhabitual drinkers. The titer of viral RNA (logarithmic transformed copy numbers per milliliter of serum) of habitual drinkers (8.5 +/- 0.5) was higher than that of nonhabitual drinkers (7.7 +/- 0.8) (p < 0.01). Neopterin levels in serum, a marker for the activation of cell-mediated immunity, were lower for habitual drinkers (5.7 +/- 1.5 pmol/ml) than for nonhabitual drinkers (8.1 +/- 5.0 pmol/ml) (p < 0.01). Eleven of the nonhabitual drinkers (30%) were long-term responders whose alanine aminotransferase levels remained within normal range during the 24 wk after interferon therapy, whereas only one (6%) of the habitual drinkers was a long-term responder (p = 0.06). These findings suggest that alcohol intake increases hepatitis C virus RNA levels in serum--at least in part--impairment of cellular immunity, and modulates the efficacy of interferon therapy.
The Brønsted acid catalyzed formal insertion of an isocyanide into a C-O bond of an acetal is described. A diverse array of acyclic and cyclic acetals can be applied to the catalytic insertion to form alpha-alkoxy imidates. Functional groups, such as nitro, cyano, halogen, ester, and alkoxy groups, are tolerant to the reaction conditions employed. The course of the reaction is highly dependent on the structure of the isocyanide. The use of an electron-deficient aryl isocyanide, such as 2c and 2d, is required to selectively obtain the monoinsertion product. When aryl isocyanides containing alkyl substituents, such as 2a and 2b, are employed, two molecules of the isocyanide are incorporated, and the double-insertion product is obtained. The reaction of tert-octyl isocyanide also induces a double incorporation, but the subsequent acid-mediated fragmentation leads to the 2-alkoxy imidoyl cyanide. The monoinsertion products, alpha-alkoxy imidates, can readily be hydrolyzed to alpha-alkoxy esters, realizing the formal carbonylation of an acetal.
The reaction of cyclic ketals or acetals with 2,6-dibromophenylisocyanide in the presence of a catalytic amount of GaCl(3) results in the insertion of isocyanide into the carbon-oxygen bond of cyclic ketals and acetals. [reaction: see text]
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