A series of og-aminoalkyl ammonium hydrogen phosphates were synthesized through a simple and efficient three-step method. The starting materials, co-aminoalkyl alcohols （AC-n, with carbon number n = 3, 4, 5, 6）, wer...A series of og-aminoalkyl ammonium hydrogen phosphates were synthesized through a simple and efficient three-step method. The starting materials, co-aminoalkyl alcohols （AC-n, with carbon number n = 3, 4, 5, 6）, were amino-protected with 9- fluorenylmethyl chloroformate （Fmoc-C1）, followed by phosphorylation with POCI3 and deprotection in piperidine/DME The structures of each intermediate and final product were confirmed by 1H NMR, FTIR and mass spectrum. The yield of each step was about 77-92%, with a total yield higher than 56%. This new method was superior in low-cost raw materials, mild reaction temperatures （0-25 ℃） and easy purification methods.展开更多
Phenylglycine 1 as a representative of natural resourceful a-amino acid was modified by reduction and protection of functional group to afford the amino alcohol as a chiral building block 3. A new chiral compound, the...Phenylglycine 1 as a representative of natural resourceful a-amino acid was modified by reduction and protection of functional group to afford the amino alcohol as a chiral building block 3. A new chiral compound, the chiral building block/spiro-cyclopropane derivative containing four stereogenic centers, compound 7, has been obtained in 52% yield with de≥98% via the tandem double Michael addition/internal nucleophilic substitution under mild condition of 5-l-menthyloxy-3-bromo-2-(5H)-furanone 4 with the nucleophilic reagent, the amino alcohol 3. The new chiral compound 7 is identified on the basis of its analytical data and spectroscopic data, such as UV, IR, 1H NMR, 13C NMR, MS and elementary analysis. The absolute configuration of the interesting spiro-cyclopropanes 7 was established by X-ray crystallography. This result can provide new route and method for the introduction of chiral building block and the important synthetic strategy in synthesis of some complex molecules containing展开更多
Al_(2)O_(3)-supported monometallic Ni,Co,and bimetallic Ni-Co nanocatalysts originated from layered double hydroxide precursors were synthesized by co-precipitation method,and used for the synthesis of useful 5-amino-...Al_(2)O_(3)-supported monometallic Ni,Co,and bimetallic Ni-Co nanocatalysts originated from layered double hydroxide precursors were synthesized by co-precipitation method,and used for the synthesis of useful 5-amino-1-pentanol(5-AP)and 1,5-pentanediol(1,5-PD)by reductive amination(RA)or direct hydrogenation of biofurfuralderived 2-hydroxytetrahydropyran(2-HTHP),respectively.In both reactions,the yield of the target products decreased monotonously with the increasing amounts of Co in the NiCo/Al_(2)O_(3)catalysts,owing probably to the replacement of highly reactive Ni by Co component with inferior hydrogenation activity at the low reaction temperature of 60℃.However,the incorporation of Co could improve the reducibility of the NiCo/Al_(2)O_(3)bimetallic catalysts and promote the reaction stability of the catalysts,especially for Ni_(2)Co1/Al_(2)O_(3),in both reactions with over 180 h time-on-stream.Characterization of the catalysts before and after the reaction showed that the incorporating Co could inhibit the sintering of metal particles and hinder the surface oxidation of the more reactive Ni0species,thanks to the formation of Ni-Co alloy in the bimetallic catalysts.DFT-based modeling of the reaction mechanisms is also performed,supporting the reaction pathway proposed previously and also the much higher activity of Ni in the RA of 2-HTHP as compared with Co.展开更多
A series of amino alcohol derivatives containing 1,3,4-oxadiazole moieties was synthesized with 7-bromo-2-tetralone as starting materials, 2,2-dimethyl-1,3-oxazolidine as intermediates and Strecker reaction and cycliz...A series of amino alcohol derivatives containing 1,3,4-oxadiazole moieties was synthesized with 7-bromo-2-tetralone as starting materials, 2,2-dimethyl-1,3-oxazolidine as intermediates and Strecker reaction and cyclization with POCt3 as key steps. The structures of the key intermediate and target compounds were confirmed by IH NMR, 13C NMR and HRMS. Some compounds have resulted in the generation of highly potent sphingosine 1-phosphate receptor type 1（S1P1） agonists.展开更多
A chiral Lewis base organocatalyzed enantioselective hydrosilylation ofa-keto ketimines was investigated.The reactions afforded various enantioenriched a-amino ketones with good yields（up to 95％） in moderate to goo...A chiral Lewis base organocatalyzed enantioselective hydrosilylation ofa-keto ketimines was investigated.The reactions afforded various enantioenriched a-amino ketones with good yields（up to 95％） in moderate to good enantioselectivities（up to 98％ e.e.）.Furthermore,one of the products was reduced to a chiral 1,2-amino alcohol.Following cyclization of it with triphosgene generated a cannabinoid receptor 1 （CB 1） inhibitor with good diastereoselectivity.展开更多
Alcohol use disorder(AUD) is one of the most widespread neuropsychiatric conditions, having a significant health and socioeconomic impact. According to the 2014 World Health Organization global status report on alcoho...Alcohol use disorder(AUD) is one of the most widespread neuropsychiatric conditions, having a significant health and socioeconomic impact. According to the 2014 World Health Organization global status report on alcohol and health, the harmful use of alcohol is responsible for 5.9% of all deaths worldwide. Additionally, 5.1% of the global burden of disease and injury is ascribed to alcohol(measured in disability adjusted life years, or disability adjusted life years). Although the neurobiological basis of AUD is highly complex, the corticostriatal circuit contributes significantly to the development of addictive behaviors. In-depth investigation into the changes of the neurotransmitters in this circuit, dopamine, gamma-aminobutyricacid, and glutamate, and their corresponding neuronal receptors in AUD and other addictions enable us to understand the molecular basis of AUD. However, these discoveries have also revealed a dearth of knowledge regarding contributions from nonneuronal sources. Astrocytes, though intimately involved in synaptic function, had until recently been noticeably overlooked in their potential role in AUD. One major function of the astrocyte is protecting neurons from excitotoxicity by removing glutamate from the synapse via excitatory amino acid transporter type 2. The importance of this key transporter in addiction, as well as ethanol withdrawal, has recently become evident, though its regulation is still under investigation. Historically, pharmacotherapy for AUD has been focused on altering the activity of neuronal glutamate receptors. However, recent clinical evidence has supported the animal-based findings, showing that regulating glutamate homeostasis contributes to successful management of recovery from AUD.展开更多
N (1 Phenyl 2 hydroxyethyl) 2,3 naphthylenedicarboximide(1a) was obtained by the reaction of 2,3 naphthylenedicarbonitrile with R phenylglycinol. 2,3 Naphthylenedicarboxylic acid, when reacts with thionyl chloride, gi...N (1 Phenyl 2 hydroxyethyl) 2,3 naphthylenedicarboximide(1a) was obtained by the reaction of 2,3 naphthylenedicarbonitrile with R phenylglycinol. 2,3 Naphthylenedicarboxylic acid, when reacts with thionyl chloride, gives 2,3 naphthalenedicarboxylic acid cyclic anhydride rather than the corresponding 2,3 naphthalenedicarboxylic acid dichloride. The former, when reacts with S leucinol, gives corresponding dicarboximide(1b). The crystal structure of compound 1a was determined by an X ray single crystal diffraction analysis. Compound 1a: C 40 H 30 N 2O 6, F W=634 66, orthorhombic, space group P 2(1)2(1)2(1), a =1 15556(5) nm, b =3 16552(12) nm, c =0 85984(3) nm; α= 90°, β=90°, γ=90°, V =3 1452(11) nm 3, Z=4, \{F(000)=\}1328, D c=1 340 g/cm 3, μ =0 091 mm -1 . Reflections collected/unique, 28053/4068( R int =0 0411); Final R indices : R 1=0 0337, wR 2=0 0687; Largest diff. peak and hole, 248 and \{-222\} e·nm -3 .展开更多
基金sponsored by the National Science Foundation of China (No. 50973069)the Scientific ResearchFoundation for the Returned Overseas Chinese Scholars,State Education Ministry (No. 20101561-3-3)
文摘A series of og-aminoalkyl ammonium hydrogen phosphates were synthesized through a simple and efficient three-step method. The starting materials, co-aminoalkyl alcohols （AC-n, with carbon number n = 3, 4, 5, 6）, were amino-protected with 9- fluorenylmethyl chloroformate （Fmoc-C1）, followed by phosphorylation with POCI3 and deprotection in piperidine/DME The structures of each intermediate and final product were confirmed by 1H NMR, FTIR and mass spectrum. The yield of each step was about 77-92%, with a total yield higher than 56%. This new method was superior in low-cost raw materials, mild reaction temperatures （0-25 ℃） and easy purification methods.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 29672004).
文摘Phenylglycine 1 as a representative of natural resourceful a-amino acid was modified by reduction and protection of functional group to afford the amino alcohol as a chiral building block 3. A new chiral compound, the chiral building block/spiro-cyclopropane derivative containing four stereogenic centers, compound 7, has been obtained in 52% yield with de≥98% via the tandem double Michael addition/internal nucleophilic substitution under mild condition of 5-l-menthyloxy-3-bromo-2-(5H)-furanone 4 with the nucleophilic reagent, the amino alcohol 3. The new chiral compound 7 is identified on the basis of its analytical data and spectroscopic data, such as UV, IR, 1H NMR, 13C NMR, MS and elementary analysis. The absolute configuration of the interesting spiro-cyclopropanes 7 was established by X-ray crystallography. This result can provide new route and method for the introduction of chiral building block and the important synthetic strategy in synthesis of some complex molecules containing
基金financially supported by the National Natural Science Foundation of China(21872155,22102198,and 22272187)the Strategic Pilot Science and Technology Project of the Chinese Academy of Sciences(XDA21010700)the CAS"Light of West China"Program
文摘Al_(2)O_(3)-supported monometallic Ni,Co,and bimetallic Ni-Co nanocatalysts originated from layered double hydroxide precursors were synthesized by co-precipitation method,and used for the synthesis of useful 5-amino-1-pentanol(5-AP)and 1,5-pentanediol(1,5-PD)by reductive amination(RA)or direct hydrogenation of biofurfuralderived 2-hydroxytetrahydropyran(2-HTHP),respectively.In both reactions,the yield of the target products decreased monotonously with the increasing amounts of Co in the NiCo/Al_(2)O_(3)catalysts,owing probably to the replacement of highly reactive Ni by Co component with inferior hydrogenation activity at the low reaction temperature of 60℃.However,the incorporation of Co could improve the reducibility of the NiCo/Al_(2)O_(3)bimetallic catalysts and promote the reaction stability of the catalysts,especially for Ni_(2)Co1/Al_(2)O_(3),in both reactions with over 180 h time-on-stream.Characterization of the catalysts before and after the reaction showed that the incorporating Co could inhibit the sintering of metal particles and hinder the surface oxidation of the more reactive Ni0species,thanks to the formation of Ni-Co alloy in the bimetallic catalysts.DFT-based modeling of the reaction mechanisms is also performed,supporting the reaction pathway proposed previously and also the much higher activity of Ni in the RA of 2-HTHP as compared with Co.
文摘A series of amino alcohol derivatives containing 1,3,4-oxadiazole moieties was synthesized with 7-bromo-2-tetralone as starting materials, 2,2-dimethyl-1,3-oxazolidine as intermediates and Strecker reaction and cyclization with POCt3 as key steps. The structures of the key intermediate and target compounds were confirmed by IH NMR, 13C NMR and HRMS. Some compounds have resulted in the generation of highly potent sphingosine 1-phosphate receptor type 1（S1P1） agonists.
基金Supported by the National Natural Science Foundation of China（No.20972155）.
文摘A chiral Lewis base organocatalyzed enantioselective hydrosilylation ofa-keto ketimines was investigated.The reactions afforded various enantioenriched a-amino ketones with good yields（up to 95％） in moderate to good enantioselectivities（up to 98％ e.e.）.Furthermore,one of the products was reduced to a chiral 1,2-amino alcohol.Following cyclization of it with triphosgene generated a cannabinoid receptor 1 （CB 1） inhibitor with good diastereoselectivity.
基金Supported by Mayo Graduate School,NIAAA,No.AA018779SC Johnson Genomics of Addiction Program,Ulm Family Foundation,Center for Individualized Medicine at MayoDavid Lehr Research Award from American Society for Pharmacology and Experimental Therapeutics
文摘Alcohol use disorder(AUD) is one of the most widespread neuropsychiatric conditions, having a significant health and socioeconomic impact. According to the 2014 World Health Organization global status report on alcohol and health, the harmful use of alcohol is responsible for 5.9% of all deaths worldwide. Additionally, 5.1% of the global burden of disease and injury is ascribed to alcohol(measured in disability adjusted life years, or disability adjusted life years). Although the neurobiological basis of AUD is highly complex, the corticostriatal circuit contributes significantly to the development of addictive behaviors. In-depth investigation into the changes of the neurotransmitters in this circuit, dopamine, gamma-aminobutyricacid, and glutamate, and their corresponding neuronal receptors in AUD and other addictions enable us to understand the molecular basis of AUD. However, these discoveries have also revealed a dearth of knowledge regarding contributions from nonneuronal sources. Astrocytes, though intimately involved in synaptic function, had until recently been noticeably overlooked in their potential role in AUD. One major function of the astrocyte is protecting neurons from excitotoxicity by removing glutamate from the synapse via excitatory amino acid transporter type 2. The importance of this key transporter in addiction, as well as ethanol withdrawal, has recently become evident, though its regulation is still under investigation. Historically, pharmacotherapy for AUD has been focused on altering the activity of neuronal glutamate receptors. However, recent clinical evidence has supported the animal-based findings, showing that regulating glutamate homeostasis contributes to successful management of recovery from AUD.
基金Supported by the National Natural Science Foundation of China(No. 2 0 172 0 0 1)
文摘N (1 Phenyl 2 hydroxyethyl) 2,3 naphthylenedicarboximide(1a) was obtained by the reaction of 2,3 naphthylenedicarbonitrile with R phenylglycinol. 2,3 Naphthylenedicarboxylic acid, when reacts with thionyl chloride, gives 2,3 naphthalenedicarboxylic acid cyclic anhydride rather than the corresponding 2,3 naphthalenedicarboxylic acid dichloride. The former, when reacts with S leucinol, gives corresponding dicarboximide(1b). The crystal structure of compound 1a was determined by an X ray single crystal diffraction analysis. Compound 1a: C 40 H 30 N 2O 6, F W=634 66, orthorhombic, space group P 2(1)2(1)2(1), a =1 15556(5) nm, b =3 16552(12) nm, c =0 85984(3) nm; α= 90°, β=90°, γ=90°, V =3 1452(11) nm 3, Z=4, \{F(000)=\}1328, D c=1 340 g/cm 3, μ =0 091 mm -1 . Reflections collected/unique, 28053/4068( R int =0 0411); Final R indices : R 1=0 0337, wR 2=0 0687; Largest diff. peak and hole, 248 and \{-222\} e·nm -3 .
