In this paper, we report that diisopropyl phosphoryl amino acid could be prepared with reasonable yields under solvent-free condition by adding amino acid to the mixture of diisopropyl phosphite and N-chlorodiisopropy...In this paper, we report that diisopropyl phosphoryl amino acid could be prepared with reasonable yields under solvent-free condition by adding amino acid to the mixture of diisopropyl phosphite and N-chlorodiisopropylamine.展开更多
The a-L-rhamnopyranosyl phosphomonoesters conjugated with L-amino acid methyl esters were stereoselectively synthesized in a convenient route by utilizing H-phosphonate intermediate.
To overcome immune tolerance to cancer,the immune system needs to be exposed to a multi-target action intervention.Here,we investigated the activating effect of CpG oligodeoxynucleotides(ODNs),mesyl phosphoramidate Cp...To overcome immune tolerance to cancer,the immune system needs to be exposed to a multi-target action intervention.Here,we investigated the activating effect of CpG oligodeoxynucleotides(ODNs),mesyl phosphoramidate CpG ODNs,anti-OX40 antibodies,and OX40 RNA aptamers on major populations of immunocompetent cells ex vivo.Comparative analysis of the antitumor effects of in situ vaccination with CpG ODNs and anti-OX40 antibodies,as well as several other combinations,such as mesyl phosphoramidate CpG ODNs and OX40 RNA aptamers,was conducted.Antibodies against programmed death 1(PD1)checkpoint inhibitors or their corresponding PD1 DNA aptamers were also added to vaccination regimens for analytical purposes.Four scenarios were considered:a weakly immunogenic Krebs-2 carcinoma grafted in CBA mice;a moderately immunogenic Lewis carcinoma grafted in C57Black/6 mice;and an immunogenic A20 B cell lymphoma or an Ehrlich carcinoma grafted in BALB/c mice.Adding anti-PD1 antibodies(CpG+αOX40+αPD1)to in situ vaccinations boosts the antitumor effect.When to be used instead of antibodies,aptamers also possess antitumor activity,although this effect was less pronounced.The strongest effect across all the tumors was observed in highly immunogenic A20 B cell lymphoma and Ehrlich carcinoma.展开更多
5,7-Dimethoxy-2-phenylquinolin-4-yl phenyloxy （N-L-alanine ethyl ester） phosphoramidate （C28H29N2O7P, Mr = 536.17） has been synthesized by a facial phosphorylated reaction, and its structure was determined by IR, ...5,7-Dimethoxy-2-phenylquinolin-4-yl phenyloxy （N-L-alanine ethyl ester） phosphoramidate （C28H29N2O7P, Mr = 536.17） has been synthesized by a facial phosphorylated reaction, and its structure was determined by IR, NMR, HR MS and X-ray single-crystal diffraction. The crystal belongs to triclinic, space group P1^-, with a = 11.375（2）, b = 11.591（2）, c = 11.638（2） A^°, α= 109.46（3）, β= 104.58（3）, γ= 100.48（3）°, V = 1339.6（5）A^°^3, Z = 2, Dc = 1.330 g/cm^3,μ = 0.152 mm^-1, F（000） = 564, the final R = 0.0654 and wR = 0.1546. In the crystal structure, the title compound is constructed by a centrosymmetric dimmer unit composed of a pair of π-π stacking diastereoisomers. The compound has a noteworthy feature in the framework, and such units are linked by two equal intermolecular P=O…H-N hydrogen bonds.展开更多
A blending chelate filter membrane with high chelate capacity for Ag + has been prepared by blending of phosphoramidic acid resin and polysulfone. The major parameters influencing structure of the chelate filter membr...A blending chelate filter membrane with high chelate capacity for Ag + has been prepared by blending of phosphoramidic acid resin and polysulfone. The major parameters influencing structure of the chelate filter membranes such as the blending ratio, phosphoramidic acid resin grain size and temperature of casting solution have been studied. The relationship among the chelate amount of Ag +, pH value, Ag + concentration and phosphoramidic acid resin grain diameter were examined. The chelate filter membrane had a capacity of 1 438 μg/cm 2 for Ag + under appropriate conditions. Sorption isotherm of Ag + could be expressed with the Freundlich sorption model. The dynamic chelate experiments proved that the sorption and desorption of membranes could be realized simultaneously for Ag +.展开更多
Novel steroidal phosphoramidate conjugates of 3＇-azido-2＇,3＇-dideoxythymidine （AZT） and amino acid esters were synthesized and determined by positive and negative ion electrospray ionization mass spectrometry. Th...Novel steroidal phosphoramidate conjugates of 3＇-azido-2＇,3＇-dideoxythymidine （AZT） and amino acid esters were synthesized and determined by positive and negative ion electrospray ionization mass spectrometry. The MS fragmentation behaviors of the steroidal phosphoramidate conjugates have been investigated in conjunction with tandem mass spectrometry of ESI-MS/MS. There were three characteristic fragment ions in the positive ion ESI mass spectra, which were the Na adduct ions with loss of steroidal moiety, amino acid ester moiety from pseudo molecular ion （M＋Na）^＋, and the phosphoamino acid methyl ester Na adduct ion by α-cleavage of the phosphora- midate respectively. The main fragment ions in negative ion ESI mass spectra were the ion （M-HN3）^-, the ion （M - AZT- H）^-, and the ion （M-steroidal moiety-H）^- besides the pseudo molecular ion （M-H）^-. The fragmentation patterns did not depend on the attached amino acid ester moiety.展开更多
Diphenyl diamine-based phosphonyl imines attached by the N-isopropyl group in the auxiliary have been synthesized in good yields under convenient reaction conditions.These new chiral N-phosphonyl imines can react with...Diphenyl diamine-based phosphonyl imines attached by the N-isopropyl group in the auxiliary have been synthesized in good yields under convenient reaction conditions.These new chiral N-phosphonyl imines can react with glycine enolate smoothly to give chiral α-β diamino esters in good yields(72%-90%) and up to excellent diastereoselectivity(】99:1 dr).By treatment with HBr,the chiral auxiliary can be readily removed.The absolute structure has been unambiguously determined by converting a product to a known sample.展开更多
Chiral N-triflyl phosphoramide was found an efficient catalyst for the enantioselective Friedel-Crafts alkylation reaction of 4,7-dihydroindole with β, γ-unsaturated a-keto esters. In the presence of 5 tool% of the ...Chiral N-triflyl phosphoramide was found an efficient catalyst for the enantioselective Friedel-Crafts alkylation reaction of 4,7-dihydroindole with β, γ-unsaturated a-keto esters. In the presence of 5 tool% of the optimized catalyst, various pyrrolo[1,2-a]indoles were obtained in excellent enantioselectivity, moderate yields and up to 3 ： 1 di- astereoselectivity based on the one-pot synthesis including the Friedel-Crafts alkylation reaction and the subsequent p-benzoquinone oxidation.展开更多
Dinucleotide (TpAZT) phosphoramidates were synthesized by Todd reaction of dinucleoside H-phosphonates and amino acid methyl esters, and their diastereomers (Rp and Sp) were separated by crystallization, and the resul...Dinucleotide (TpAZT) phosphoramidates were synthesized by Todd reaction of dinucleoside H-phosphonates and amino acid methyl esters, and their diastereomers (Rp and Sp) were separated by crystallization, and the results showed that natural and cheap methyl esters of alanine and phenylalanine can be used for large-scale synthesis of dinucleotide analogs.展开更多
Two chiral phosporamidates, (R)-(–)-1, 1′-binaphthyl-2, 2′dihydroxy-N- [α-(S)-methylbenzyl] phosphoramidate and (–)-1,1′-biphenyl-2,2′-dihydroxy-N-[α-(S)-methylbenzyl]-phosphoramidate were synthesized. Their c...Two chiral phosporamidates, (R)-(–)-1, 1′-binaphthyl-2, 2′dihydroxy-N- [α-(S)-methylbenzyl] phosphoramidate and (–)-1,1′-biphenyl-2,2′-dihydroxy-N-[α-(S)-methylbenzyl]-phosphoramidate were synthesized. Their crystal structures were determined by X-ray single crystal diffraction analysis. The phosphoramidate molecules are self-associated by intermolecular NH ···O = P hydrogen bonds and aromatic edge to face interactions.展开更多
基金the National Natural Science Foundation of china (Grand No.20132020) for financial support the Ministry of Science and Technology the Chinese Ministry of Education and Tsinghua University
文摘In this paper, we report that diisopropyl phosphoryl amino acid could be prepared with reasonable yields under solvent-free condition by adding amino acid to the mixture of diisopropyl phosphite and N-chlorodiisopropylamine.
基金The authors would like to thank the financial supports from the NNSF of China(No.201 72033),the Ministry of Science and Technology,the Ministry of Education and Tsinghua University.
文摘The a-L-rhamnopyranosyl phosphomonoesters conjugated with L-amino acid methyl esters were stereoselectively synthesized in a convenient route by utilizing H-phosphonate intermediate.
基金supported by the Russian Ministry of Science and High Education via the Institute of Cytology and Genetics (State Budget Project No.FWNR-2022-0016)the Russian Foundation for Basic Research (Grant No.18-29-09045).
文摘To overcome immune tolerance to cancer,the immune system needs to be exposed to a multi-target action intervention.Here,we investigated the activating effect of CpG oligodeoxynucleotides(ODNs),mesyl phosphoramidate CpG ODNs,anti-OX40 antibodies,and OX40 RNA aptamers on major populations of immunocompetent cells ex vivo.Comparative analysis of the antitumor effects of in situ vaccination with CpG ODNs and anti-OX40 antibodies,as well as several other combinations,such as mesyl phosphoramidate CpG ODNs and OX40 RNA aptamers,was conducted.Antibodies against programmed death 1(PD1)checkpoint inhibitors or their corresponding PD1 DNA aptamers were also added to vaccination regimens for analytical purposes.Four scenarios were considered:a weakly immunogenic Krebs-2 carcinoma grafted in CBA mice;a moderately immunogenic Lewis carcinoma grafted in C57Black/6 mice;and an immunogenic A20 B cell lymphoma or an Ehrlich carcinoma grafted in BALB/c mice.Adding anti-PD1 antibodies(CpG+αOX40+αPD1)to in situ vaccinations boosts the antitumor effect.When to be used instead of antibodies,aptamers also possess antitumor activity,although this effect was less pronounced.The strongest effect across all the tumors was observed in highly immunogenic A20 B cell lymphoma and Ehrlich carcinoma.
基金supported by the National Natural Science Foundation of China (No. 20472076, 20572061, 20732004)Henan Academic Foundation of Science and Technology (No. 0512001400)
文摘5,7-Dimethoxy-2-phenylquinolin-4-yl phenyloxy （N-L-alanine ethyl ester） phosphoramidate （C28H29N2O7P, Mr = 536.17） has been synthesized by a facial phosphorylated reaction, and its structure was determined by IR, NMR, HR MS and X-ray single-crystal diffraction. The crystal belongs to triclinic, space group P1^-, with a = 11.375（2）, b = 11.591（2）, c = 11.638（2） A^°, α= 109.46（3）, β= 104.58（3）, γ= 100.48（3）°, V = 1339.6（5）A^°^3, Z = 2, Dc = 1.330 g/cm^3,μ = 0.152 mm^-1, F（000） = 564, the final R = 0.0654 and wR = 0.1546. In the crystal structure, the title compound is constructed by a centrosymmetric dimmer unit composed of a pair of π-π stacking diastereoisomers. The compound has a noteworthy feature in the framework, and such units are linked by two equal intermolecular P=O…H-N hydrogen bonds.
文摘A blending chelate filter membrane with high chelate capacity for Ag + has been prepared by blending of phosphoramidic acid resin and polysulfone. The major parameters influencing structure of the chelate filter membranes such as the blending ratio, phosphoramidic acid resin grain size and temperature of casting solution have been studied. The relationship among the chelate amount of Ag +, pH value, Ag + concentration and phosphoramidic acid resin grain diameter were examined. The chelate filter membrane had a capacity of 1 438 μg/cm 2 for Ag + under appropriate conditions. Sorption isotherm of Ag + could be expressed with the Freundlich sorption model. The dynamic chelate experiments proved that the sorption and desorption of membranes could be realized simultaneously for Ag +.
基金Project supported by the National Natural Science Foundation of China （No. 20542004）, the Specialized Research Fund for the Doctoral Program of Higher Education （No. 20050003104）, and the Beijing Commission of Education （No. XK 100030514）.
文摘Novel steroidal phosphoramidate conjugates of 3＇-azido-2＇,3＇-dideoxythymidine （AZT） and amino acid esters were synthesized and determined by positive and negative ion electrospray ionization mass spectrometry. The MS fragmentation behaviors of the steroidal phosphoramidate conjugates have been investigated in conjunction with tandem mass spectrometry of ESI-MS/MS. There were three characteristic fragment ions in the positive ion ESI mass spectra, which were the Na adduct ions with loss of steroidal moiety, amino acid ester moiety from pseudo molecular ion （M＋Na）^＋, and the phosphoamino acid methyl ester Na adduct ion by α-cleavage of the phosphora- midate respectively. The main fragment ions in negative ion ESI mass spectra were the ion （M-HN3）^-, the ion （M - AZT- H）^-, and the ion （M-steroidal moiety-H）^- besides the pseudo molecular ion （M-H）^-. The fragmentation patterns did not depend on the attached amino acid ester moiety.
基金supported by the National Institutes of Health (Grant Nos.1 RO3 DA026960-01)Robert Welch Foundation (Grant No.D-1361)
文摘Diphenyl diamine-based phosphonyl imines attached by the N-isopropyl group in the auxiliary have been synthesized in good yields under convenient reaction conditions.These new chiral N-phosphonyl imines can react with glycine enolate smoothly to give chiral α-β diamino esters in good yields(72%-90%) and up to excellent diastereoselectivity(】99:1 dr).By treatment with HBr,the chiral auxiliary can be readily removed.The absolute structure has been unambiguously determined by converting a product to a known sample.
文摘Chiral N-triflyl phosphoramide was found an efficient catalyst for the enantioselective Friedel-Crafts alkylation reaction of 4,7-dihydroindole with β, γ-unsaturated a-keto esters. In the presence of 5 tool% of the optimized catalyst, various pyrrolo[1,2-a]indoles were obtained in excellent enantioselectivity, moderate yields and up to 3 ： 1 di- astereoselectivity based on the one-pot synthesis including the Friedel-Crafts alkylation reaction and the subsequent p-benzoquinone oxidation.
基金The authors would like to thank the financial supports from the National Natural Science Foundation of China(No.29902003,20132020 and 20175026),the Ministry of Science and Technology,the Chinese Ministry of Education and Tsinghua University.
文摘Dinucleotide (TpAZT) phosphoramidates were synthesized by Todd reaction of dinucleoside H-phosphonates and amino acid methyl esters, and their diastereomers (Rp and Sp) were separated by crystallization, and the results showed that natural and cheap methyl esters of alanine and phenylalanine can be used for large-scale synthesis of dinucleotide analogs.
基金Project supported by the National Natural Science Foundation of China (Grant No. 29872023)the Ministry of Education of China (Research Funds for Chinese Scholars returning from abroad)China Postdoctoral Science Foundation
文摘Two chiral phosporamidates, (R)-(–)-1, 1′-binaphthyl-2, 2′dihydroxy-N- [α-(S)-methylbenzyl] phosphoramidate and (–)-1,1′-biphenyl-2,2′-dihydroxy-N-[α-(S)-methylbenzyl]-phosphoramidate were synthesized. Their crystal structures were determined by X-ray single crystal diffraction analysis. The phosphoramidate molecules are self-associated by intermolecular NH ···O = P hydrogen bonds and aromatic edge to face interactions.
