Carbamoyl-phosphate synthase plays a vital role in the carbon and nitrogen metabolism cycles. In Xanthomonas citrisubsp. citri, carA and carB encode the small and large subunits of carbamoyl-phosphate synthase, respec...Carbamoyl-phosphate synthase plays a vital role in the carbon and nitrogen metabolism cycles. In Xanthomonas citrisubsp. citri, carA and carB encode the small and large subunits of carbamoyl-phosphate synthase, respectively. The deletion mutation of the coding regions revealed that carA did not affect any of the phenotypes, while carB played multiple roles in pathogenicity. The deletion of carB rendered the loss of pathogenicity in host plants and the ability to induce a hyper- sensitive reaction in the non-hosts. Quantitative reverse transcription-PCR assays indicated that 11 hrp genes coding the type Ill secretion system were suppressed when interacting with citrus plants. The mutation in carB also affected bacterial utilization of several carbon and nitrogen resources in minimal medium MMX and extracellular enzyme activities. These data demonstrated that only the large subunit of carbamoyl-phosphate synthase was essential for canker development by X. citri subsp, citri.展开更多
Eighteen 2′,4′-difluoro-3-（carbamoyl）biphenyl-4-yl benzoates were synthesized from diflunisal in three steps with total yields from 72% to 86%. All compounds were identified by IR, 1^H NMR, MS and elemental analys...Eighteen 2′,4′-difluoro-3-（carbamoyl）biphenyl-4-yl benzoates were synthesized from diflunisal in three steps with total yields from 72% to 86%. All compounds were identified by IR, 1^H NMR, MS and elemental analysis. The anti-inflammatory activity and analgesic activity for 18 compounds were evaluated. The preliminary assay results showed that compounds 4a and 4p exhibited potent anti-inflammatory-analgesic activity.展开更多
A practical one-pot preparation of carbamoyl fluorides from easily obtained pyridine N-oxide,commercially available secondary amines and synthetically versatile difluorocarbene precursors(Ruppert-Prakash reagent or Ch...A practical one-pot preparation of carbamoyl fluorides from easily obtained pyridine N-oxide,commercially available secondary amines and synthetically versatile difluorocarbene precursors(Ruppert-Prakash reagent or Chen's reagent)was developed herein,which dexterously resorted to the oxidation of difluorocarbene by external pyridine N-oxide to produce the toxic and gaseous fluorophosgene in situ.Notable features of this method include nice functionality tolerance,late-stage modification of drug molecules and the recoveryand recycle of quinoline.展开更多
Carbamoyl phosphate synthetase i （CPS1） deficiency （CPS1D） is an inborn error of the urea cycle having autosomal （2q34） recessive inheritance that can cause hyperammonemia and neonatal death or mental retardatio...Carbamoyl phosphate synthetase i （CPS1） deficiency （CPS1D） is an inborn error of the urea cycle having autosomal （2q34） recessive inheritance that can cause hyperammonemia and neonatal death or mental retardation. We analyzed the effects on CPS1 activity, kinetic parameters and enzyme stability of missense mutations reported in patients with CPS1 deficiency that map in the 20-kDa C-terminal domain of the enzyme. This domain turns on or off the enzyme depending on whether the essential allosteric activator of CPS 1, N-acetyl- L-glutamate （NAG）, is bound or is not bound to it. To carry out the present studies, we exploited a novel system that allows the expression in vitro and the purification of human CPS1, thus permitting site-directed mutagenesis. These studies have clarified disease causation by individual mutations, identifying functionally important residues, and revealing that a number of mutations decrease the affinity of the enzyme for NAG. Patients with NAG affinity-decreasing mutations might benefit from NAG site saturation therapy with N-carbamyl-L- glutamate （a registered drug, the analog of NAG）. Our results, together with additional present and prior site-directed mutagenesis data for other residues mapping in this domain, suggest an NAG-triggered conformational change in the 134-~4 loop of the C-terminal domain of this enzyme. This change might be an early event in the NAG activation process. Molecular dynamics simulations that were restrained according to the observed effects of the mutations are consistent with this hypothesis, providing further backing for this structurally plausible signaling mechanism by which NAG could trigger urea cycle activation via CPS1.展开更多
We present an efficient, fast and simple strategy of generating the intermediate carbamoyl chlorides from secondary amines using stoichiometric amounts of bis（trichloromethyl）carbonate （BTC） in solution and solven...We present an efficient, fast and simple strategy of generating the intermediate carbamoyl chlorides from secondary amines using stoichiometric amounts of bis（trichloromethyl）carbonate （BTC） in solution and solvent-free conditions with excellent yields. The results obtained showed the yield increasing on whether a base was used. Finally, an efficient and rapid synthesis of variety carbamate derivatives was developed by the reaction with a high variety of different alcohols, phenols, diols and this intermediate at room temperature with grinding and in solvent-free conditions under microwave irradiation. The presence of various safe bases is shown to be effective in reducing the reaction times, increasing the yields and easing purification. The present method does not involve any hazardous phosgene.展开更多
An efficient KI catalyzed nitrogenation of aldehydes and alcohols for the direct synthesis of carbamoyl azides and ureas via a radical process has been developed. The simple operating procedures, the readily available...An efficient KI catalyzed nitrogenation of aldehydes and alcohols for the direct synthesis of carbamoyl azides and ureas via a radical process has been developed. The simple operating procedures, the readily available starting materials including aldehydes, alcohols and amines, as well as the utility of the products all make this strategy very attractive.展开更多
Borylative cyclization of E-3-arylallyl carbamoyl chlorides is achieved through copper catalyzed intramolecular carboboration with B_(2)pin_(2).2-Aryl-3-boryl-γ-lactams are formed with exclusive cisdiastereoselectivi...Borylative cyclization of E-3-arylallyl carbamoyl chlorides is achieved through copper catalyzed intramolecular carboboration with B_(2)pin_(2).2-Aryl-3-boryl-γ-lactams are formed with exclusive cisdiastereoselectivity.CuBr-Dppp combination gives the best outcomes.The substrate scope is profiled.展开更多
Herein we report a nickel-catalyzed asymmetric two-component reductive aryl-acylation and arylcarbamoylation of aryl-iodide-tethered unactivated alkenes,which utilize ortho-pyridinyl esters and isocyanates as the elec...Herein we report a nickel-catalyzed asymmetric two-component reductive aryl-acylation and arylcarbamoylation of aryl-iodide-tethered unactivated alkenes,which utilize ortho-pyridinyl esters and isocyanates as the electrophilic acyl sources,respectively.Under the catalysis of a nickel–pyrox complex with zinc powder as the reductant,a variety of chiral indanes,indolines,and dihydrobenzofurans bearing a quaternary stereogenic center were prepared in moderate to high efficiency and good to excellent enantioselectivities.The utility of this method is demonstrated by various simple derivatizations of the attached carbonyl group,particularly the sequential benzylic oxidation and pinacol coupling,which provide a concise entry to the benzene-fused bicyclic bridged ring framework containing three challenging tetrasubstituted stereocenters in high stereocontrol.展开更多
In order to get good antitumor agents especially better than 5-fluorouracil,tegafur and l-hexylcarbamoyl-5-fluorouracil (HCFU),fourty nine 1-carbamoyl-5-fluorouracil having aromatic ring were synthesized from 5-fluoro...In order to get good antitumor agents especially better than 5-fluorouracil,tegafur and l-hexylcarbamoyl-5-fluorouracil (HCFU),fourty nine 1-carbamoyl-5-fluorouracil having aromatic ring were synthesized from 5-fluorouracil and isocyanates or amines.Antitumor activity was tested in the L-1210 tumor system,and 5 compounds gave better value of therapeutic ratio than 5-fluorouracil,tegafur,HCFU.l-(4-Methoxybenzylcarbamoyl)-5-fluorouracil gave the best result.展开更多
In sharp contrast to the well researched and well developed aminocarbonylation of alkenes,the dearomative carbamoylation of abundant areneπ-systems has scarcely been studied despite its great potential to enrich the ...In sharp contrast to the well researched and well developed aminocarbonylation of alkenes,the dearomative carbamoylation of abundant areneπ-systems has scarcely been studied despite its great potential to enrich the diversity-oriented synthesis of high-value amides.The formidable challenges associated with such dearomatization include the low reactivity of stable aromaticπ-systems and intricate selectivity issues.Herein,we disclose a general approach toward highly selective dearomative carbamoylations of areneπ-bonds under CO-gas-free conditions.Its extraordinary versatility was demonstrated by tolerating a broad range of nucleophilic partners with high yields and excellent selectivities,thus providing modular access to the divergent synthesis ofβ-functionalized primary amides.In addition,diverse downstream derivatizations including a formal C–H 1,2-olefination/carbamoylation reaction were conducted,exhibiting great potential in synthetic and medicinal chemistry.展开更多
基金supported by the National Natural Science Foundation of China (31171832)the Special Fund for Agro-Scientific Research in the Public Interest, China (201003067)
文摘Carbamoyl-phosphate synthase plays a vital role in the carbon and nitrogen metabolism cycles. In Xanthomonas citrisubsp. citri, carA and carB encode the small and large subunits of carbamoyl-phosphate synthase, respectively. The deletion mutation of the coding regions revealed that carA did not affect any of the phenotypes, while carB played multiple roles in pathogenicity. The deletion of carB rendered the loss of pathogenicity in host plants and the ability to induce a hyper- sensitive reaction in the non-hosts. Quantitative reverse transcription-PCR assays indicated that 11 hrp genes coding the type Ill secretion system were suppressed when interacting with citrus plants. The mutation in carB also affected bacterial utilization of several carbon and nitrogen resources in minimal medium MMX and extracellular enzyme activities. These data demonstrated that only the large subunit of carbamoyl-phosphate synthase was essential for canker development by X. citri subsp, citri.
基金the Opening Foundation of The Biochemical Engineering Key Discipline (No.20050105) Zhejiang,China,for financial supportthe National Center for Drug Screening,Shanghai,China,for evaluation of anti-inflammatory and analgesic activity.
文摘Eighteen 2′,4′-difluoro-3-（carbamoyl）biphenyl-4-yl benzoates were synthesized from diflunisal in three steps with total yields from 72% to 86%. All compounds were identified by IR, 1^H NMR, MS and elemental analysis. The anti-inflammatory activity and analgesic activity for 18 compounds were evaluated. The preliminary assay results showed that compounds 4a and 4p exhibited potent anti-inflammatory-analgesic activity.
基金The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China(grant no.22271151)and the Distinguished Youth Foundation of Jiangsu Province.
文摘A practical one-pot preparation of carbamoyl fluorides from easily obtained pyridine N-oxide,commercially available secondary amines and synthetically versatile difluorocarbene precursors(Ruppert-Prakash reagent or Chen's reagent)was developed herein,which dexterously resorted to the oxidation of difluorocarbene by external pyridine N-oxide to produce the toxic and gaseous fluorophosgene in situ.Notable features of this method include nice functionality tolerance,late-stage modification of drug molecules and the recoveryand recycle of quinoline.
基金supported by grants from the Alicia Koplowitz Foundation, the Valencian government (No. Prometeo II/2014/ 029 to V.R.)the Spanish government (Nos. BFU2011-30407 to V.R., BFU2012-30770 to J.G. and a FPU fellowship to C.D.-F.)the Swiss National Science Foundation (No. 310030_127184 to J.H.)
文摘Carbamoyl phosphate synthetase i （CPS1） deficiency （CPS1D） is an inborn error of the urea cycle having autosomal （2q34） recessive inheritance that can cause hyperammonemia and neonatal death or mental retardation. We analyzed the effects on CPS1 activity, kinetic parameters and enzyme stability of missense mutations reported in patients with CPS1 deficiency that map in the 20-kDa C-terminal domain of the enzyme. This domain turns on or off the enzyme depending on whether the essential allosteric activator of CPS 1, N-acetyl- L-glutamate （NAG）, is bound or is not bound to it. To carry out the present studies, we exploited a novel system that allows the expression in vitro and the purification of human CPS1, thus permitting site-directed mutagenesis. These studies have clarified disease causation by individual mutations, identifying functionally important residues, and revealing that a number of mutations decrease the affinity of the enzyme for NAG. Patients with NAG affinity-decreasing mutations might benefit from NAG site saturation therapy with N-carbamyl-L- glutamate （a registered drug, the analog of NAG）. Our results, together with additional present and prior site-directed mutagenesis data for other residues mapping in this domain, suggest an NAG-triggered conformational change in the 134-~4 loop of the C-terminal domain of this enzyme. This change might be an early event in the NAG activation process. Molecular dynamics simulations that were restrained according to the observed effects of the mutations are consistent with this hypothesis, providing further backing for this structurally plausible signaling mechanism by which NAG could trigger urea cycle activation via CPS1.
文摘We present an efficient, fast and simple strategy of generating the intermediate carbamoyl chlorides from secondary amines using stoichiometric amounts of bis（trichloromethyl）carbonate （BTC） in solution and solvent-free conditions with excellent yields. The results obtained showed the yield increasing on whether a base was used. Finally, an efficient and rapid synthesis of variety carbamate derivatives was developed by the reaction with a high variety of different alcohols, phenols, diols and this intermediate at room temperature with grinding and in solvent-free conditions under microwave irradiation. The presence of various safe bases is shown to be effective in reducing the reaction times, increasing the yields and easing purification. The present method does not involve any hazardous phosgene.
基金Financial support from National Basic Research Program of China （973 Program） （No. 2015CB856600）, the National Natural Science Foundation of China （Nos. 21325206, 21632001）, National Young Top-notch Talent Support Program, CAS Interdisciplinary Innovation Team, and Peking University Health Science Center （Nos. BMU20150505, BMU20160541） is greatly ap- preciated. We thank Bencong Zhu and Ao Sun in this group for reproducing the results of 2a and 2k.
文摘An efficient KI catalyzed nitrogenation of aldehydes and alcohols for the direct synthesis of carbamoyl azides and ureas via a radical process has been developed. The simple operating procedures, the readily available starting materials including aldehydes, alcohols and amines, as well as the utility of the products all make this strategy very attractive.
基金the National Natural Science Foundation of China(No.21672027)for financial supportsupported by High-Level Entrepreneurial Talent Team of Jiangsu Province(No.2017-37)。
文摘Borylative cyclization of E-3-arylallyl carbamoyl chlorides is achieved through copper catalyzed intramolecular carboboration with B_(2)pin_(2).2-Aryl-3-boryl-γ-lactams are formed with exclusive cisdiastereoselectivity.CuBr-Dppp combination gives the best outcomes.The substrate scope is profiled.
基金supported by start-up funds from the Young Scholar 1000 Talents Planthe National Natural Science Foundation of China(21772183 and 22071230)+2 种基金the Fundamental Research Funds for the Central Universities(WK2060190086)the Project Funded by China Postdoctoral Science Foundation(2020M682006)the University of Science and Technology of China.
文摘Herein we report a nickel-catalyzed asymmetric two-component reductive aryl-acylation and arylcarbamoylation of aryl-iodide-tethered unactivated alkenes,which utilize ortho-pyridinyl esters and isocyanates as the electrophilic acyl sources,respectively.Under the catalysis of a nickel–pyrox complex with zinc powder as the reductant,a variety of chiral indanes,indolines,and dihydrobenzofurans bearing a quaternary stereogenic center were prepared in moderate to high efficiency and good to excellent enantioselectivities.The utility of this method is demonstrated by various simple derivatizations of the attached carbonyl group,particularly the sequential benzylic oxidation and pinacol coupling,which provide a concise entry to the benzene-fused bicyclic bridged ring framework containing three challenging tetrasubstituted stereocenters in high stereocontrol.
文摘In order to get good antitumor agents especially better than 5-fluorouracil,tegafur and l-hexylcarbamoyl-5-fluorouracil (HCFU),fourty nine 1-carbamoyl-5-fluorouracil having aromatic ring were synthesized from 5-fluorouracil and isocyanates or amines.Antitumor activity was tested in the L-1210 tumor system,and 5 compounds gave better value of therapeutic ratio than 5-fluorouracil,tegafur,HCFU.l-(4-Methoxybenzylcarbamoyl)-5-fluorouracil gave the best result.
基金the National Natural Science Foundation of China(grant no.22271251)the Fundamental Research Funds for the Central Universities(grant nos.226-2023-00016,226-2023-00115,and 226-2022-00224).
文摘In sharp contrast to the well researched and well developed aminocarbonylation of alkenes,the dearomative carbamoylation of abundant areneπ-systems has scarcely been studied despite its great potential to enrich the diversity-oriented synthesis of high-value amides.The formidable challenges associated with such dearomatization include the low reactivity of stable aromaticπ-systems and intricate selectivity issues.Herein,we disclose a general approach toward highly selective dearomative carbamoylations of areneπ-bonds under CO-gas-free conditions.Its extraordinary versatility was demonstrated by tolerating a broad range of nucleophilic partners with high yields and excellent selectivities,thus providing modular access to the divergent synthesis ofβ-functionalized primary amides.In addition,diverse downstream derivatizations including a formal C–H 1,2-olefination/carbamoylation reaction were conducted,exhibiting great potential in synthetic and medicinal chemistry.
