Abstract Iron‐catalyzed asymmetric amination of C(sp 3 )−H bonds is appealing for synthetic applications due to the biocompatibility and high earth abundance of iron, but examples of such reactions are sparse. Herein we describe chiral iron complexes of meso ‐ and β ‐substituted‐porphyrins that can catalyze asymmetric intramolecular C(sp 3 )−H amination of aryl and arylsulfonyl azides to afford chiral indolines (29 examples) and benzofused cyclic sulfonamides (17 examples), respectively, with up to 93 % ee (yield: up to 99 %) using 410 nm light under mild conditions. Mechanistic studies, including DFT calculations, for the reactions of arylsulfonyl azides reveal that the Fe(NSO 2 Ar) intermediate generated in situ under photochemical conditions reacts with the C(sp 3 )−H bond through a stepwise hydrogen atom transfer/radical rebound mechanism, with enantioselectivity arising from cooperative noncovalent interactions between the Fe(NSO 2 Ar) unit and the peripheral substituents of the chiral porphyrin scaffold.
Gaucher disease is an autosomal recessive lysosomal storage disorder caused by the deficient activity of glucocerebrosidase. Accumulation of glucosylceramide, primarily in the lysosomes of cells of the reticuloendothelial system, leads to hepatosplenomegaly, anemia and skeletal lesions in type I disease, and neurologic manifestations in types II and III disease. We report herein the identification of hydrophilic active‐site‐specific chaperones that are capable of increasing glucocerebrosidase activity in the cultured fibroblasts of Gaucher patients. Screening of a variety of natural and synthetic alkaloid compounds showed isofagomine, N ‐dodecyl deoxynojirimycin, calystegines A 3 , B 1 , B 2 and C 1 , and 1,5‐dideoxy‐1,5‐iminoxylitol to be potent inhibitors of glucocerebrosidase. Among them, isofagomine was the most potent inhibitor of glucocerebrosidase in vitro , and the most effective active‐site‐specific chaperone capable of increasing residual glucocerebrosidase activity in fibroblasts established from Gaucher patients with the most prevalent Gaucher disease‐causing mutation (N370S). Intracellular enzyme activity increased approximately two‐fold after cells had been incubated with isofagomine, and the increase in glucocerebrosidase activity was both dose‐dependent and time‐dependent. Western blotting demonstrated that there was a substantial increase in glucocerebrosidase protein in cells after isofagomine treatment. Immunocytochemistry revealed an improvement in the glucocerebrosidase trafficking pattern, which overlaps that of lysosome‐associated membrane protein 2 in Gaucher fibroblasts cultivated with isofagomine, suggesting that the transport of mutant glucocerebrosidase is at least partially improved in the presence of isofagomine. The hydrophilic active‐site‐specific chaperones are less toxic to cultured cells. These results indicate that these hydrophilic small molecules are suitable candidates for further drug development for the treatment of Gaucher disease.
With the rapid growth of population and industrial production, wastewater pollution has become a major environmental issue. Wastewater pollution also poses a threat to water resources and human health. Catalytic wet-air oxidation (CWAO) is one of the most economical and environmentally friendly technologies, especially for the treatment of toxic and non-biodegradable pollutants in wastewater. Various heterogeneous catalysts have been reported for use in wastewater treatment; however, most of these catalysts are effective only under high temperatures and high pressures. The increasing demand for the removal of wastewater pollutants necessitates the development of low-temperature, high-efficiency catalysts for CWAO technology. To achieve this, the ability of the catalyst to activate O
A carboxyl proteinase was purified from rice koji of Aspergillus kawachii to a homogeneous state on polyacrylamide gel electrophoresis. The molecular weight and isoelectric point of the enzyme were 35,000 and 3.9, respectively. The enzyme was most active between pH 2.8 and 3.4 with hemoglobin as substrate, and stable in the pH range of 2.2 ~ 6.4. The optimum temperature of the enzyme reaction was at 50°C. The serine content was highest and no methionine was found in the enzyme. The enzyme was inhibited by typical inhibitors for carboxyl proteinases such as DAN, EPNP, and SPI.
An efficient method has been developed for the asymmetric intramolecular C(sp3)−H amination of aryl and arylsulfonyl azides to give chiral indolines and benzofused cyclic sulfonamides in high product yields and with excellent enantioselectivities under mild reaction conditions, as reported by Li Dang, Yungen Liu, Chi-Ming Che and co-workers in their Research Article (e202218577). This method provides a complementary approach to asymmetric C(sp3)−H aminations by precious metal-based catalysis.
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