Chiral monodentate phosphoramidite ligands were conveniently prepared from 1,1＇-bi-2-naphthol （BINOL） and （S）-pyrrolidine in good yields, which were effective chiral ligands in the enantioselective rhodium-cataly...Chiral monodentate phosphoramidite ligands were conveniently prepared from 1,1＇-bi-2-naphthol （BINOL） and （S）-pyrrolidine in good yields, which were effective chiral ligands in the enantioselective rhodium-catalyzed hydrogenation of dehydroamino esters and enamides at low hydrogenation pressure. High conversion rate （up to 99% for dehydroamino esters and enamides） and good enantioselectivity （up to 96.3% ee for dehy- droamino esters and 91.7% ee for enamides） were obtained.展开更多
Two new C2-symmetrical bidentate phosphoramidite ligands were synthesized and employed in the Rh-catalyzed asymmetric hydrogenation of β-（acylamino）acrylates, up to 89% ee with full conversions was obtained.
Comprehensive Summary.To overcome the depurination challenges associated with classical DNA synthesis methods,this study introduces a novel approach using fluoride-sensitive,triisopropylsilyl(TIPS)-protected phosphora...Comprehensive Summary.To overcome the depurination challenges associated with classical DNA synthesis methods,this study introduces a novel approach using fluoride-sensitive,triisopropylsilyl(TIPS)-protected phosphoramidite monomers for the efficient synthesis of short single-stranded DNA.The bulky TIPS group selectively protects the 5'-hydroxyl group of nucleosides and can be rapidly removed under mild,non-acidic conditions using fluoride ions,minimizing side reactions.Four novel TIPS-protected phosphoramidite monomers were synthesized and characterized,achieving>99%deprotection efficiency.These monomers were applied to the solid-phase synthesis of a 5-mer ssDNA sequence,yielding an overall efficiency of 99%for each cycle.The strategy demonstrates significant potential for improving the reliability and scalability of oligonucleotide synthesis,offering a promising alternative for applications in synthetic biology and nucleic acid research.展开更多
Chain elongation via dinucleotide(dimer)block coupling was considered as an improved chemical technique capable of synthesizing high-quality longer oligonucleotide for de novo DNA synthesis in synthetic biology.Howeve...Chain elongation via dinucleotide(dimer)block coupling was considered as an improved chemical technique capable of synthesizing high-quality longer oligonucleotide for de novo DNA synthesis in synthetic biology.However,this dimer block-wise approach was constrained by readily available dimer phosphoramidite with sufficient quality.Herein,through the usage of a one-pot coupling-oxidation-deprotection cascade process for preparing the key precursors 3'-hydroxyl dimers,then condensation with phosphorodiamidite,purification by flash column chromatography and precipation in methyl tert-butyl ether,a rationally designed dimer phosphoramidite bearing an internucleotide allyl phosphate and aβ-cyanoethyl phosphoramidite at the 3’-hydroxyl was synthesized.All sixteen allylic dimer phosphoramidites 2a-p were smoothly prepared with overall yields exceeding 50%and HPLC purities ranging from 97.40%to 99.69%.With these allylic reagents,oligonucleotides were successfully synthesized using a modified solid-phase phosphoramidite method and were completely deprotected under normal ammonialysis condition.Our results indicated that these dimer block-wise synthesized oligonucleotides were of sufficient quality for gene assembly and protein expression,thus,the allylic phosphate linked dimer phosphoramidite can serve as a promising dimer reagent that will enable the applications of long oligonucleotides.展开更多
Reversible protein phosphorylation is of great importance in the regulation of many cellular processes. Structurally well defined compounds are needed for the study of the roles of the phospho proteins in biologica...Reversible protein phosphorylation is of great importance in the regulation of many cellular processes. Structurally well defined compounds are needed for the study of the roles of the phospho proteins in biological processes. In this paper, O phosphorylated oligopeptides were synthesized using bis alkyloxy N,N dialkylphosphoramidite reacting with the oligopeptide followed by oxidation. Many hydroxyl groups in oligopeptides can be phosphorylated in one step.展开更多
Phosphopeptides were synthesized with bis-alkyloxy-N,N-dialkylphosphorfollowed by oxidation. Many hydroxyl groups in oligopeptides can be O-phosphorylated in onestep.
A facile and efficient protocol for the synthesis of sulfur substituted-cyclopyrophosphate of cIDPRE（P_S^1-cIDPRE） was developed.The key step was the cyclization process which was completed by the sulfur substituted...A facile and efficient protocol for the synthesis of sulfur substituted-cyclopyrophosphate of cIDPRE（P_S^1-cIDPRE） was developed.The key step was the cyclization process which was completed by the sulfur substituted cyclization precursor 1b via the one-pot phosphoramidite strategy.展开更多
A highly efficient kinetic resolution of racemic thioanilide atropisomers via C(sp^(3))-H arylation has been achieved by a hybrid palladium catalyst bearing an anionic chiral Co^(Ⅲ)-complex and a phosphoramidite liga...A highly efficient kinetic resolution of racemic thioanilide atropisomers via C(sp^(3))-H arylation has been achieved by a hybrid palladium catalyst bearing an anionic chiral Co^(Ⅲ)-complex and a phosphoramidite ligand,leading to both enantioenriched atropisomeric arylation thioanilides(up to 99%ee)and N-Me atropisomeric thioanilides(up to 99%ee),simultaneously.The remained enantioenriched substrates can be arylated again by using an achiral anionic ligand to give the enantiomer with the opposite configuration.展开更多
An iridium-catalyzed allylic substitution of sodium phenyl selenide with unsymmetrical allyl carbonates was accomplished, which produced the linear allyl phenyl selenides in 38%--74% yields. An asymmetric irid- ium-ca...An iridium-catalyzed allylic substitution of sodium phenyl selenide with unsymmetrical allyl carbonates was accomplished, which produced the linear allyl phenyl selenides in 38%--74% yields. An asymmetric irid- ium-catalyzed allylation of sodium phenyl selenide was presented as well.展开更多
The direct functionalization of allylic C-H bonds is distinguished by enabling rapid assembly of structural complexity from simple molecules.Although Pd-catalyzed allylic C-H functionalization has been extensively stu...The direct functionalization of allylic C-H bonds is distinguished by enabling rapid assembly of structural complexity from simple molecules.Although Pd-catalyzed allylic C-H functionalization has been extensively studied,the discovery of new catalytic systems remains fairly underdeveloped.Here,we disclose a Pt-catalyzed allylic C-H alkylation of a wide range of α-alkenes by using phosphoramidites as ligands and malononitriles as alkylating reagents.Notably,the combination of chiral ureacatalyzed Michael addition and Pt-catalyzed allylic C-H alkylation can serve as an efficient protocol to access chiral tetrahydropyran with high levels of diastereo-and enantioselectivity.Mechanistic studies suggest that the Pt-catalyzed allylic C-H activation proceeds through a concerted proton and two-electron transfer process,which is analogous to transition state geometries of Pd catalysis.展开更多
The identification of hydroxylmethyl- and formylpyrimidines in genomic DNA was a landmark event in epigenetics. Numerous laboratories in related fields are investigating the biology of these and other nucleic acid mod...The identification of hydroxylmethyl- and formylpyrimidines in genomic DNA was a landmark event in epigenetics. Numerous laboratories in related fields are investigating the biology of these and other nucleic acid modifications. However, limitations in the ability to detect and synthesize appropriate modifications are an impediment. Herein, we explored a remarkable development in the selective detection of 5-formyluracil in both single-stranded and double-stranded DNA under mild conditions. The ＂switch-on＂ specificity towards 5-formyluracil enabled a high signal-to-noise ratio in qualitatively and quantitatively detecting materials containing 5-formyluradl, which is not affected by the presence of abasic sites and 5-formylcytosine, the modified cytosine counterpart of 5-formyluracil. In summar~ the innoxiousness, convenience, and cost-effidency of the 5-formyluracil phosphoramidite synthetic routine would promote the understanding of the epi^enetic role of this natural thvmidine modification.展开更多
Large scale synthesis of oligoribonucleotides has been successfully performed on PEG support by the phosphoramidite approach using t-butyldimethylsilyl to protect the 2'-hydroxyl group of ribonucleoside. By means ...Large scale synthesis of oligoribonucleotides has been successfully performed on PEG support by the phosphoramidite approach using t-butyldimethylsilyl to protect the 2'-hydroxyl group of ribonucleoside. By means of this procedure, the dodecamer r(AGUGGUCUUUGU) was synthesized in 98.1% average coupling yield, and 55 mg pure product was obtained from one gram of functionalized PEG.展开更多
The combination of hydrophobic polymers with nucleic acids is a fascinating way to engineer the self-assembly behavior of nucleic acids into diverse nanostructures such as micelles,vesicles,nanosheets,and worms.Here w...The combination of hydrophobic polymers with nucleic acids is a fascinating way to engineer the self-assembly behavior of nucleic acids into diverse nanostructures such as micelles,vesicles,nanosheets,and worms.Here we developed a robust route to synthesize a RNA macroinitiator with protecting groups on the 2′-hydroxyl groups in the solid phase using an oligonucleotide synthesizer.The protecting groups successfully solubilized the RNA macroinitiator,enabling atom transfer radical polymerization(ATRP)of hydrophobic monomers.As a result,the RNA−polymer hybrids obtained by ATRP exhibited enhanced chemical stability by suppressing cleavage.In addition,we demonstrated evidence of controlled polymerization behavior as well as control over the molecular weight of the hydrophobic polymers grown from RNA.We envision that this methodology will expand the field of RNA−polymer conjugates while vastly enhancing the possibility to alter and engineer the properties of RNA-based polymeric materials.展开更多
基金Supported by the National Natural Science Foundation of China (20572101)
文摘Chiral monodentate phosphoramidite ligands were conveniently prepared from 1,1＇-bi-2-naphthol （BINOL） and （S）-pyrrolidine in good yields, which were effective chiral ligands in the enantioselective rhodium-catalyzed hydrogenation of dehydroamino esters and enamides at low hydrogenation pressure. High conversion rate （up to 99% for dehydroamino esters and enamides） and good enantioselectivity （up to 96.3% ee for dehy- droamino esters and 91.7% ee for enamides） were obtained.
基金The authors would like to thank the National Natural Science Foundation of China （No. 20472083） for financial support of this work.
文摘Two new C2-symmetrical bidentate phosphoramidite ligands were synthesized and employed in the Rh-catalyzed asymmetric hydrogenation of β-（acylamino）acrylates, up to 89% ee with full conversions was obtained.
基金supported by the National Key R&D Program of China(No.2018YFA0902300)the Grants from the Key Project of the Medical and Health Science and Technology Plan of Zhejiang Province(WKJ-ZJ-2547)+2 种基金the National Natural Science Foundation of China(21991080)Zhejiang Provincial Science and Technology Plan Project(2024SDYXS0002)the Independent Deployment Project of the Hangzhou Institute of Medicine,Chinese Academy of Sciences(2024ZZBS03).
文摘Comprehensive Summary.To overcome the depurination challenges associated with classical DNA synthesis methods,this study introduces a novel approach using fluoride-sensitive,triisopropylsilyl(TIPS)-protected phosphoramidite monomers for the efficient synthesis of short single-stranded DNA.The bulky TIPS group selectively protects the 5'-hydroxyl group of nucleosides and can be rapidly removed under mild,non-acidic conditions using fluoride ions,minimizing side reactions.Four novel TIPS-protected phosphoramidite monomers were synthesized and characterized,achieving>99%deprotection efficiency.These monomers were applied to the solid-phase synthesis of a 5-mer ssDNA sequence,yielding an overall efficiency of 99%for each cycle.The strategy demonstrates significant potential for improving the reliability and scalability of oligonucleotide synthesis,offering a promising alternative for applications in synthetic biology and nucleic acid research.
基金supported by the National Key Research and Development Program of China(No.2018YFA0902300)。
文摘Chain elongation via dinucleotide(dimer)block coupling was considered as an improved chemical technique capable of synthesizing high-quality longer oligonucleotide for de novo DNA synthesis in synthetic biology.However,this dimer block-wise approach was constrained by readily available dimer phosphoramidite with sufficient quality.Herein,through the usage of a one-pot coupling-oxidation-deprotection cascade process for preparing the key precursors 3'-hydroxyl dimers,then condensation with phosphorodiamidite,purification by flash column chromatography and precipation in methyl tert-butyl ether,a rationally designed dimer phosphoramidite bearing an internucleotide allyl phosphate and aβ-cyanoethyl phosphoramidite at the 3’-hydroxyl was synthesized.All sixteen allylic dimer phosphoramidites 2a-p were smoothly prepared with overall yields exceeding 50%and HPLC purities ranging from 97.40%to 99.69%.With these allylic reagents,oligonucleotides were successfully synthesized using a modified solid-phase phosphoramidite method and were completely deprotected under normal ammonialysis condition.Our results indicated that these dimer block-wise synthesized oligonucleotides were of sufficient quality for gene assembly and protein expression,thus,the allylic phosphate linked dimer phosphoramidite can serve as a promising dimer reagent that will enable the applications of long oligonucleotides.
文摘Reversible protein phosphorylation is of great importance in the regulation of many cellular processes. Structurally well defined compounds are needed for the study of the roles of the phospho proteins in biological processes. In this paper, O phosphorylated oligopeptides were synthesized using bis alkyloxy N,N dialkylphosphoramidite reacting with the oligopeptide followed by oxidation. Many hydroxyl groups in oligopeptides can be phosphorylated in one step.
文摘Phosphopeptides were synthesized with bis-alkyloxy-N,N-dialkylphosphorfollowed by oxidation. Many hydroxyl groups in oligopeptides can be O-phosphorylated in onestep.
基金scientific research funding from the National Natural Science Foundation of China(Nos.21332010,21172010, 21002004)
文摘A facile and efficient protocol for the synthesis of sulfur substituted-cyclopyrophosphate of cIDPRE（P_S^1-cIDPRE） was developed.The key step was the cyclization process which was completed by the sulfur substituted cyclization precursor 1b via the one-pot phosphoramidite strategy.
基金We are grateful for the financial support from NSFC(Grant No.21831007).
文摘A highly efficient kinetic resolution of racemic thioanilide atropisomers via C(sp^(3))-H arylation has been achieved by a hybrid palladium catalyst bearing an anionic chiral Co^(Ⅲ)-complex and a phosphoramidite ligand,leading to both enantioenriched atropisomeric arylation thioanilides(up to 99%ee)and N-Me atropisomeric thioanilides(up to 99%ee),simultaneously.The remained enantioenriched substrates can be arylated again by using an achiral anionic ligand to give the enantiomer with the opposite configuration.
文摘An iridium-catalyzed allylic substitution of sodium phenyl selenide with unsymmetrical allyl carbonates was accomplished, which produced the linear allyl phenyl selenides in 38%--74% yields. An asymmetric irid- ium-catalyzed allylation of sodium phenyl selenide was presented as well.
基金The financial support from the National Nature Science Foundation of China(NSFC)(nos.21831007 and 21672197 for L.-Z.G.and nos.21702182 and 21873081 for X.H.)the Chinese Academy of Sciences(grant no.XDB20020000)+1 种基金Youth Innovation Promotion Association CAS,Fundamental Research Funds for the Central Universities(no.2020XZZX002-02 for X.H.)the State Key Laboratory of Clean Energy Utilization(no.ZJUCEU2020007 for X.H.)is gratefully acknowledged.
文摘The direct functionalization of allylic C-H bonds is distinguished by enabling rapid assembly of structural complexity from simple molecules.Although Pd-catalyzed allylic C-H functionalization has been extensively studied,the discovery of new catalytic systems remains fairly underdeveloped.Here,we disclose a Pt-catalyzed allylic C-H alkylation of a wide range of α-alkenes by using phosphoramidites as ligands and malononitriles as alkylating reagents.Notably,the combination of chiral ureacatalyzed Michael addition and Pt-catalyzed allylic C-H alkylation can serve as an efficient protocol to access chiral tetrahydropyran with high levels of diastereo-and enantioselectivity.Mechanistic studies suggest that the Pt-catalyzed allylic C-H activation proceeds through a concerted proton and two-electron transfer process,which is analogous to transition state geometries of Pd catalysis.
基金We thank the National Basic Research Program of China （Nos. 2012CB720600 and 2012CB720603）, the National Natural Science Foundation of China （Nos. 21432008, 91413109, and 81373256）.
文摘The identification of hydroxylmethyl- and formylpyrimidines in genomic DNA was a landmark event in epigenetics. Numerous laboratories in related fields are investigating the biology of these and other nucleic acid modifications. However, limitations in the ability to detect and synthesize appropriate modifications are an impediment. Herein, we explored a remarkable development in the selective detection of 5-formyluracil in both single-stranded and double-stranded DNA under mild conditions. The ＂switch-on＂ specificity towards 5-formyluracil enabled a high signal-to-noise ratio in qualitatively and quantitatively detecting materials containing 5-formyluradl, which is not affected by the presence of abasic sites and 5-formylcytosine, the modified cytosine counterpart of 5-formyluracil. In summar~ the innoxiousness, convenience, and cost-effidency of the 5-formyluracil phosphoramidite synthetic routine would promote the understanding of the epi^enetic role of this natural thvmidine modification.
文摘Large scale synthesis of oligoribonucleotides has been successfully performed on PEG support by the phosphoramidite approach using t-butyldimethylsilyl to protect the 2'-hydroxyl group of ribonucleoside. By means of this procedure, the dodecamer r(AGUGGUCUUUGU) was synthesized in 98.1% average coupling yield, and 55 mg pure product was obtained from one gram of functionalized PEG.
基金NSF DMR 2202747 and DTRA grant HDTRA1-20-1-0014.G.S.gratefully acknowledges the Polish National Agency for Academic Exchange(BPN/PPO/2022/1/00027)for financial support。
文摘The combination of hydrophobic polymers with nucleic acids is a fascinating way to engineer the self-assembly behavior of nucleic acids into diverse nanostructures such as micelles,vesicles,nanosheets,and worms.Here we developed a robust route to synthesize a RNA macroinitiator with protecting groups on the 2′-hydroxyl groups in the solid phase using an oligonucleotide synthesizer.The protecting groups successfully solubilized the RNA macroinitiator,enabling atom transfer radical polymerization(ATRP)of hydrophobic monomers.As a result,the RNA−polymer hybrids obtained by ATRP exhibited enhanced chemical stability by suppressing cleavage.In addition,we demonstrated evidence of controlled polymerization behavior as well as control over the molecular weight of the hydrophobic polymers grown from RNA.We envision that this methodology will expand the field of RNA−polymer conjugates while vastly enhancing the possibility to alter and engineer the properties of RNA-based polymeric materials.
