Selectfluor-Promoted Intramolecular N-S Bond Formation of α-Carbamoyl Ketene Dithioacetals in the Presence of Water: Synthesis of Multifunctionalized Isothiazolones.

A practical and efficient protocol toward fully substituted isothiazolones through Selectfluor-mediated intramolecular oxidative annulation of α-carbamoyl ketene dithioacetals has been developed in the presence of H2O and metal-free conditions. Notably, the experimental results reveal that H2O was crucial to the formation of new N-S bonds and the elimination of alkyl group from the sulfur atom. This protocol provides readily prepared substrates and possesses good functional group tolerance, mild reaction conditions, and operational simplicity, which provides potential access to applications in the pharmaceutical chemistry.

Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21(WAF1) expression and hepatic apoptosis.

AIM:To detect the expression of caspase 3 gene in primary human hepatocellular carcinoma (HCC) and investigate its relationship top21(WAF1) gene expression and HCC apoptosis.METHODS:In situ hybridization was employed to determine caspase 3 and p21(WAF1) expression in HCC.In situ end-labeling was used to detect hepatocytic apoptosis in HCC.RESULTS:Twenty-one of 39 (53.8%) cases of HCC were found to express caspase 3 transcripts, while 46.2% of HCC failed to express caspase 3.Non-cancerous adjacent liver tissues showed more positive caspase 3(87.5%, 7/8) as compared with HCC (p < 0.05). The expression of caspase 3 is correlated with HCC differentiation, 72.2% (13/18) of moderately to highly differentiated HCC showed caspase 3 transcripts positive, while only 38.1% of poorly differentiated HCC harbored caspase 3 transcripts (italic>p < 0.05). No relationship was found between caspase 3 expression and tumor size or grade or metastasis, although 62.5% (5/8) of HCC with metastasis were caspase 3 positive and a little higher than that with no metastasis (51.6%, p> 0.05). Expression of caspase 3 alone did not affect the apoptosis index (AI) of HCC. The AI was 7.12 in caspase 3 positive tumors (n = 21), while in caspase 3-negative cases (n = 18) 6.59 (italic>p > 0.05). Expression of caspase 3 clearly segregated with p21(WAF1) positive tumors as compared with p21(WAF1) negative cases (16 of 23, 69.6% versus 5 of 16, 31.3%) with statistical significance (p = 0.017).In the cases with positive caspase 3 and negative p21(WAF1), the AI was found slightly higher, but with no statistical significance, than that with expres-sion of p21(WAF1) and caspase 3 (7.21 vs 6.98 , p>0.05).CONCLUSION:Loss of caspase 3 expression may contribute to HCC carcinogenesis, although the expression of caspase 3 does not correlate well with cell apoptosis in HCC.p21(WAF1) may be merely one of the inhibitors which can reduce caspase 3 mediated cell apoptosis in HCCs.