The pyrrole-derived alkaloids with marine origin, especially their permethyl derivatives, have unique structures and promising biological activities. Marine natural product neolamellarins are a collection of lamellari...The pyrrole-derived alkaloids with marine origin, especially their permethyl derivatives, have unique structures and promising biological activities. Marine natural product neolamellarins are a collection of lamellarin-like phenolic pyrrole compounds, which can inhibit hypoxia-induced HIF-1 activation. Many pyrrole-derived lamellarin-like alkaloids show potent MDR reversing activity. In this study, five permethylated derivatives of neolamellarin A were synthesized with their MDR reversing activity studied in order to identify new MDR reversal agents. A convergent strategy was adopted to synthesize the permethylated derivatives of neolamellarin A. Pyrrole was first converted into a corresponding N-trisisopropylsilyl （TIPS）-substituted derivative, then through iodination afforded 3,4-diiodinated pyrrole compound. The key intermediate, 3,4-disubstituent-lH-pyrrole, was obtained through desilylation of 3,4-disubstituent-l-TIPS pyrrole, which was prepared from 3,4-diiodinated pyrrole derivative and aryl boronic acid ester through Suzuki cross-coupling reaction between them. Then, the intermediate, 3,4-disubstituent-lH-pyrrole, reacted with fresh phenylacetyl chloride under n-BuLi/THF condition afforded the target compounds. Finally, we obtained five novel pyrrolic com- pounds, permethylated derivatives ofneolamellarin A 16a-e, in 30%-37% yield through five step reactions. The bioactivity testing of these compounds are in process.展开更多
Caspase-1-mediated IL-1β production is generally controlled by two pathways. Toll-like receptors （TLRs） recognize pathogen-derived products and induce NF-KB-dependent pro-IL-1β transcription; NOD-like receptors （...Caspase-1-mediated IL-1β production is generally controlled by two pathways. Toll-like receptors （TLRs） recognize pathogen-derived products and induce NF-KB-dependent pro-IL-1β transcription; NOD-like receptors （NLRs） assemble caspase-l-activating inflammasome complexes that sense bacterial products/danger signals. Through a targeted chemical screen, we identify bromoxone, a marine natural product, as a specifc and potent inhibitor of the caspase-1 pathway. Bromoxone is effective over diverse inflammatory stimuli including TLR ligands plus ATP/nigeri- cin, cytosolic DNA, flagellin and Bacillus anthracis lethal toxin. Bromoxone also efficiently suppresses easpase-1 acti- vation triggered by several types of bacterial infection. Bromoxone acts upstream or at the level of the inflammasome in a transcription-independent manner. Bromoxone also inhibits pro-IL-1β expression by targeting components up- stream of IKK in the TLR-NF-kB pathway. The unique dual activities of bromoxone are shared by the known TAK1 inhibitor that specifically blocks Nalp3 inflammasome activation. Hinted from the mechanistic and pharmacological properties of bromoxone, we further discover that several known NF-KB inhibitors that act upstream of IKK, but not those targeting IKK or IKK downstream, are potent blockers of different NLRs-mediated caspase-1 activation. Our study uncovers a possible non-transcriptional molecular link between the NLR （Nalp3）-mediated inflammasome pathway and TLR-NF-kB signaling, and suggests a potential strategy to develop new anti-inflammatory drugs.展开更多
Aim To determine the structure of the by-product produced in Grignard reaction for preparing mifepristone derivatives, and elucidate the reaction mechanism.Methods The structure of the by-product was determined with e...Aim To determine the structure of the by-product produced in Grignard reaction for preparing mifepristone derivatives, and elucidate the reaction mechanism.Methods The structure of the by-product was determined with elemental analysis, one- and two-dimension spectra NMR (DEPT, 1H-1Hcosy, HMQC, HMBC) and compared with those of mifepristone.Results The main by-product was 11,17-di-addition product of Grignard reagent of N, N-dimethylamino phenyl bromide.Conclusion This is the first complete assignment of 1H NMR and 13C NMR of compound (3).展开更多
On the base of benzimidazole and benzofuran containing heterocyclic system, several derivatives with expected biological activity were synthesized. 2,3-diaminodibenzofuran was the primary substance. Adding various cyc...On the base of benzimidazole and benzofuran containing heterocyclic system, several derivatives with expected biological activity were synthesized. 2,3-diaminodibenzofuran was the primary substance. Adding various cyclic agents, 2-phenil was got, 2-（o-chlorophenil）, 2-（o-oxyphenil）, 2-chlorometyl- and 2-hydroximethyl-3H-benzo[b[furo（3,2-f] benzimidazoles. The aforementioned substances were characterized by IR and NMR spectroscopy.展开更多
目的了解北京市售乳制品和饮料中9种双酚二缩水甘油醚的污染水平。方法采用超高效液相色谱-串联质谱法测定北京市162份乳制品及饮料样品中双酚A二缩水甘油醚(bisphenol A diglycidyl ether, BADGE)、双酚F二缩水甘油醚(bisphenol F digl...目的了解北京市售乳制品和饮料中9种双酚二缩水甘油醚的污染水平。方法采用超高效液相色谱-串联质谱法测定北京市162份乳制品及饮料样品中双酚A二缩水甘油醚(bisphenol A diglycidyl ether, BADGE)、双酚F二缩水甘油醚(bisphenol F diglycidyl ether, BFDGE)及其衍生物的含量。结果 BADGE的水解产物BADGE·2H_(2)O的检出率最高(85.2%),含量<0.80~1370.37μg/kg,其次为BADGE的氯化衍生物BADGE·H;O·HCl,检出率为33.3%,含量<0.80~85.37μg/kg。此外还检出BADGE·H;O、BADGE、BADGE·2HCl、BFDGE和BFDGE·2H_(2)O。BADGE及其衍生物在乳制品和饮料中的含量未超过欧盟EC/1895/2005规定的限量值。金属罐装样品中BADGE·2H_(2)O的含量(<0.80~1370.37μg/kg)显著高于非金属罐装样品(<0.80~7.24μg/kg)。金属罐装样品中BADGE·2H_(2)O的含量水平为液体样品>半固体样品>固体样品。BADGE·2H_(2)O在酒精类饮料和非酒精类饮料中的含量差异无统计学意义。结论北京市售金属罐装饮料中BADGE及其衍生物的污染最为严重,BADGE·2H_(2)O在非金属罐装样品中有较高的检出率,提示金属罐装材料不是这类化合物的唯一污染来源。展开更多
In this paper,we continue to study the normality of a family of meromorphic functions without simple zeros and simple poles such that their derivatives omit a given holomorphic function.Such a family in general is not...In this paper,we continue to study the normality of a family of meromorphic functions without simple zeros and simple poles such that their derivatives omit a given holomorphic function.Such a family in general is not normal at the zeros of the omitted function.Our main result is the characterization of the non-normal sequences,and hence some known results are its corollaries.展开更多
基金supported by the National Natural Science Foundation of China (21171154 and 91129706)Special Fund for Marine Scientific Research in the Public Interest (01005024)
文摘The pyrrole-derived alkaloids with marine origin, especially their permethyl derivatives, have unique structures and promising biological activities. Marine natural product neolamellarins are a collection of lamellarin-like phenolic pyrrole compounds, which can inhibit hypoxia-induced HIF-1 activation. Many pyrrole-derived lamellarin-like alkaloids show potent MDR reversing activity. In this study, five permethylated derivatives of neolamellarin A were synthesized with their MDR reversing activity studied in order to identify new MDR reversal agents. A convergent strategy was adopted to synthesize the permethylated derivatives of neolamellarin A. Pyrrole was first converted into a corresponding N-trisisopropylsilyl （TIPS）-substituted derivative, then through iodination afforded 3,4-diiodinated pyrrole compound. The key intermediate, 3,4-disubstituent-lH-pyrrole, was obtained through desilylation of 3,4-disubstituent-l-TIPS pyrrole, which was prepared from 3,4-diiodinated pyrrole derivative and aryl boronic acid ester through Suzuki cross-coupling reaction between them. Then, the intermediate, 3,4-disubstituent-lH-pyrrole, reacted with fresh phenylacetyl chloride under n-BuLi/THF condition afforded the target compounds. Finally, we obtained five novel pyrrolic com- pounds, permethylated derivatives ofneolamellarin A 16a-e, in 30%-37% yield through five step reactions. The bioactivity testing of these compounds are in process.
文摘Caspase-1-mediated IL-1β production is generally controlled by two pathways. Toll-like receptors （TLRs） recognize pathogen-derived products and induce NF-KB-dependent pro-IL-1β transcription; NOD-like receptors （NLRs） assemble caspase-l-activating inflammasome complexes that sense bacterial products/danger signals. Through a targeted chemical screen, we identify bromoxone, a marine natural product, as a specifc and potent inhibitor of the caspase-1 pathway. Bromoxone is effective over diverse inflammatory stimuli including TLR ligands plus ATP/nigeri- cin, cytosolic DNA, flagellin and Bacillus anthracis lethal toxin. Bromoxone also efficiently suppresses easpase-1 acti- vation triggered by several types of bacterial infection. Bromoxone acts upstream or at the level of the inflammasome in a transcription-independent manner. Bromoxone also inhibits pro-IL-1β expression by targeting components up- stream of IKK in the TLR-NF-kB pathway. The unique dual activities of bromoxone are shared by the known TAK1 inhibitor that specifically blocks Nalp3 inflammasome activation. Hinted from the mechanistic and pharmacological properties of bromoxone, we further discover that several known NF-KB inhibitors that act upstream of IKK, but not those targeting IKK or IKK downstream, are potent blockers of different NLRs-mediated caspase-1 activation. Our study uncovers a possible non-transcriptional molecular link between the NLR （Nalp3）-mediated inflammasome pathway and TLR-NF-kB signaling, and suggests a potential strategy to develop new anti-inflammatory drugs.
文摘Aim To determine the structure of the by-product produced in Grignard reaction for preparing mifepristone derivatives, and elucidate the reaction mechanism.Methods The structure of the by-product was determined with elemental analysis, one- and two-dimension spectra NMR (DEPT, 1H-1Hcosy, HMQC, HMBC) and compared with those of mifepristone.Results The main by-product was 11,17-di-addition product of Grignard reagent of N, N-dimethylamino phenyl bromide.Conclusion This is the first complete assignment of 1H NMR and 13C NMR of compound (3).
文摘On the base of benzimidazole and benzofuran containing heterocyclic system, several derivatives with expected biological activity were synthesized. 2,3-diaminodibenzofuran was the primary substance. Adding various cyclic agents, 2-phenil was got, 2-（o-chlorophenil）, 2-（o-oxyphenil）, 2-chlorometyl- and 2-hydroximethyl-3H-benzo[b[furo（3,2-f] benzimidazoles. The aforementioned substances were characterized by IR and NMR spectroscopy.
文摘目的了解北京市售乳制品和饮料中9种双酚二缩水甘油醚的污染水平。方法采用超高效液相色谱-串联质谱法测定北京市162份乳制品及饮料样品中双酚A二缩水甘油醚(bisphenol A diglycidyl ether, BADGE)、双酚F二缩水甘油醚(bisphenol F diglycidyl ether, BFDGE)及其衍生物的含量。结果 BADGE的水解产物BADGE·2H_(2)O的检出率最高(85.2%),含量<0.80~1370.37μg/kg,其次为BADGE的氯化衍生物BADGE·H;O·HCl,检出率为33.3%,含量<0.80~85.37μg/kg。此外还检出BADGE·H;O、BADGE、BADGE·2HCl、BFDGE和BFDGE·2H_(2)O。BADGE及其衍生物在乳制品和饮料中的含量未超过欧盟EC/1895/2005规定的限量值。金属罐装样品中BADGE·2H_(2)O的含量(<0.80~1370.37μg/kg)显著高于非金属罐装样品(<0.80~7.24μg/kg)。金属罐装样品中BADGE·2H_(2)O的含量水平为液体样品>半固体样品>固体样品。BADGE·2H_(2)O在酒精类饮料和非酒精类饮料中的含量差异无统计学意义。结论北京市售金属罐装饮料中BADGE及其衍生物的污染最为严重,BADGE·2H_(2)O在非金属罐装样品中有较高的检出率,提示金属罐装材料不是这类化合物的唯一污染来源。
基金supported by National Natural Science Foundation of China(Grant No.11171045)
文摘In this paper,we continue to study the normality of a family of meromorphic functions without simple zeros and simple poles such that their derivatives omit a given holomorphic function.Such a family in general is not normal at the zeros of the omitted function.Our main result is the characterization of the non-normal sequences,and hence some known results are its corollaries.
