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Ling Song - One of the best experts on this subject based on the ideXlab platform.
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chemo and enantioselective addition and β hydrogen transfer reduction of carbonyl compounds with diethylzinc reagent in one pot catalyzed by a single chiral organometallic catalyst
Journal of Organic Chemistry, 2015Co-Authors: Huayin Huang, Guangling Bian, Hua Zong, Ling SongAbstract:Using a single chiral Phosphoramide–Zn(II) complex as the catalyst, the asymmetric β-H transfer reduction of aromatic α-trifluoromethyl ketones and enantioselective addition of aromatic aldehydes with Et2Zn in one pot were successfully realized, affording the corresponding additive products of secondary alcohols in high yields (up to 99%) with excellent enantioselectivities (up to 98% ee) and the reduction products of α-trifluoromethyl alcohols in good to excellent yields with up to 77% ee.
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investigation on the asymmetric addition reactions between varied nonaromatic aldehydes and diethylzinc catalyzed by chiral Phosphoramide and thiophosphorodiamide ligands
Tetrahedron Letters, 2015Co-Authors: Huayin Huang, Guangling Bian, Hua Zong, Ling SongAbstract:The asymmetric addition reactions between varied nonaromatic aldehydes and diethylzinc catalyzed by chiral Phosphoramide L1 and thiophosphorodiamide L4 were thoroughly investigated. Both ligands worked very well for α-branched aliphatic and α-branched α,β-unsaturated aldehydes. For α-nonbranched aliphatic aldehydes, L4 behaved much better than L1. For α-nonbranched α,β-unsaturated aldehydes, L4 showed high enantioselectivities and L1 only gave racemic alcohol products.
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highly efficient asymmetric additions of diethylzinc to aldehydes triply activated by chiral Phosphoramide zn ii complexes derived from cinchona alkaloids
Chirality, 2013Co-Authors: Bin Shen, Huayin Huang, Guangling Bian, Hua Zong, Ling SongAbstract:New chiral Phosphoramide ligands derived from cinchona alkaloids were developed, which react with diethylzinc to form chiral Phosphoramide-Zn(II) complexes containing two Lewis bases and one Lewis acid. These trifunctional complexes can serve as highly efficient chiral catalysts for triple activation of enantioselective addition reactions of diethylzinc with aldehydes to give desired alcohol products with excellent yields and enantiomeric excess (ee) values up to 99%. Chirality 25:561-566, 2013. © 2013 Wiley Periodicals, Inc.
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synergistic effect of achiral quaternary ammonium salt on asymmetric additions of diethylzinc to aldehydes
Tetrahedron Letters, 2013Co-Authors: Hua Zong, Huayin Huang, Guangling Bian, Ling SongAbstract:Abstract Our investigation has shown that achiral quaternary ammonium salt has a significant synergistic effect on the asymmetric additions of diethylzinc to aldehydes catalyzed by chiral Phosphoramide–Zn(II) complex. The addition of 10 mol % NBu 4 X can dramatically reduce the loading amount of chiral ligand without sacrificing the excellent reactivity and enantioselectivity of the asymmetric reaction.
Jian Zhou - One of the best experts on this subject based on the ideXlab platform.
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h bond donor directed switching of diastereoselectivity in the michael addition of α azido ketones to nitroolefins
Chemical Science, 2020Co-Authors: Peigang Ding, Jinsheng Yu, Jian Zhou, Feng Zhou, Xin Wang, Qiuhua ZhaoAbstract:The development of catalyst-controlled stereodivergent asymmetric catalysis is important for providing facile access to all stereoisomers of chiral products with multiple stereocenters from the same starting materials. Despite progress, new design strategies for diastereodivergent asymmetric catalysis are still highly desirable. Here we report the potency of H-bond donors as the governing factor to tune diastereoselectivity in a highly diastereoselective switchable enantioselective Michael addition of α-azido ketones to nitroolefins. While a newly developed bifunctional tertiary amine, Phosphoramide, preferentially afforded syn-adducts, an analogous squaramide catalyst selectively gave anti-adducts. The resulting multifunctional tertiary azides can be converted to spiro-pyrrolidines with four continuous stereocenters in a one-pot operation. Mechanistic studies cast light on the control of diastereoselectivity by H-bond donors. While the squaramide-catalyzed reaction proceeded with a transition state with both squaramide N–H bonds binding to an enolate intermediate, an unprecedented model was proposed for the Phosphoramide-mediated reaction wherein an amide N–H bond and an alkylammonium ion formed in situ interact with nitroolefins, with the enolate stabilized by nonclassical C–H⋯O hydrogen-bonding interactions.
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michael addition catalyzed by chiral secondary amine Phosphoramide using fluorinated silyl enol ethers formation of quaternary carbon stereocenters
Angewandte Chemie, 2015Co-Authors: Jinsheng Yu, Fumin Liao, Kui Liao, Jian ZhouAbstract:A chiral secondary amine Phosphoramide was developed and identified as a powerful catalyst for the Mukaiyama–Michael addition of fluorinated enol silyl ethers to tetrasubstituted olefins. The resulting products are obtained with high enantioselectivities and contain a quaternary carbon stereocenter bearing either a difluoroalkyl or monofluoroalkyl group.
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highly enantioselective michael addition of 3 arylthio and 3 alkylthiooxindoles to nitroolefins catalyzed by a simple cinchona alkaloid derived Phosphoramide
ChemInform, 2015Co-Authors: Weiming Gao, Feng Zhou, Yulei Zhao, Yunlin Liu, Jian ZhouAbstract:A new cinchona alkaloid derived bifunctional tertiary amine-Phosphoramide C1e is identified as a highly enantioselective catalyst for Michael addition of both unprotected 3-arylthio- and 3-alkylthiooxindoles to nitroolefins. The Phosphoramide moiety of C1e plays an indispensable role in this reaction.
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cinchona alkaloid based Phosphoramide catalyzed highly enantioselective michael addition of unprotected 3 substituted oxindoles to nitroolefins
ChemInform, 2012Co-Authors: Miao Ding, Feng Zhou, Cuihong Wang, Xiaoli Zhao, Jian ZhouAbstract:A cinchonidine derived, bifunctional Phosphoramide is shown to catalyze the title reaction with up to 95% ds.
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cinchona alkaloid based Phosphoramide catalyzed highly enantioselective michael addition of unprotected 3 substituted oxindoles to nitroolefins
Chemical Science, 2011Co-Authors: Miao Ding, Feng Zhou, Cuihong Wang, Xiaoli Zhao, Jian ZhouAbstract:A newly developed cinchonidine-derived Phosphoramide 6b, simple and easily available, was identified as a powerful catalyst for the highly enantioselective Michael addition of both unprotected 3-aryl and 3-alkyloxindoles to β-substituted nitroalkenes to furnish the C3 quaternary stereogenic carbon center with an adjacent tertiary stereocenter in up to 21 : 1 diastereoselectivity and up to 99% enantioselectivity.
Hisashi Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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design of chiral n triflyl Phosphoramide as a strong chiral bronsted acid and its application to asymmetric diels alder reaction
Journal of the American Chemical Society, 2006Co-Authors: Daisuke Nakashima, Hisashi YamamotoAbstract:A highly reactive and acidic chiral Bronsted acid catalyst, chiral N-triflyl Phosphoramide, was developed. Highly enantioselective Diels−Alder reaction of α,β-unsaturated ketone with silyloxydiene was demonstrated using this chiral Bronsted acid catalyst.
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design of chiral n triflyl Phosphoramide as a strong chiral bronsted acid and its application to asymmetric diels alder reaction
Journal of the American Chemical Society, 2006Co-Authors: Daisuke Nakashima, Hisashi YamamotoAbstract:A highly reactive and acidic chiral Bronsted acid catalyst, chiral N-triflyl Phosphoramide, was developed. Highly enantioselective Diels-Alder reaction of alpha,beta-unsaturated ketone with silyloxydiene was demonstrated using this chiral Bronsted acid catalyst.
Yongying Jiang - One of the best experts on this subject based on the ideXlab platform.
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peptide conjugates of 4 aminocyclophosphamide as prodrugs of Phosphoramide mustard for selective activation by prostate specific antigen psa
Bioorganic & Medicinal Chemistry, 2013Co-Authors: Yongying JiangAbstract:Abstract In our continued effort to develop prodrugs of Phosphoramide mustard, conjugates of 4-aminocyclophosphamide (4-NH 2 -CPA) with three PSA-specific peptides were synthesized and evaluated as substrates of PSA. These include conjugates of cis -(2 R ,4 R )-4-NH 2 -CPA with a tetrapeptide Succinyl-Ser-Lys-Leu-Gln-OH, a hexapeptide Succinyl-His-Ser-Ser-Lys-Leu-Gln-OH, and a pentapeptide Glutaryl-Hyp-Ala-Ser-Chg-Gln-OH. These conjugates were cleaved by PSA efficiently and exclusively after the expected glutamine residue to release 4-NH 2 -CPA, the activated prodrug form of Phosphoramide mustard. The cleavage was most efficient for the pentapeptide conjugate 3 (Glutaryl-Hyp-Ala-Ser-Chg-Gln-NH-CPA), which showed a half-life of 55 min with PSA, followed by the hexapeptide conjugate 2 (Succinyl-His-Ser-Ser-Lys-Leu-Gln-NH-CPA) and the tertrapeptide conjugate 1 (Succinyl-Ser-Lys-Leu-Gln-NH-CPA) with half-lives of 6.5 and 12 h, respectively. These results indicate a potential of the conjugate 3 as an anticancer prodrug of Phosphoramide mustard for selective PSA activation.
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synthesis and stereochemical preference of peptide 4 aminocyclophosphamide conjugates as potential prodrugs of Phosphoramide mustard for activation by prostate specific antigen psa
Bioorganic & Medicinal Chemistry Letters, 2009Co-Authors: Yongying Jiang, Robert S DipaolaAbstract:In an effort to develop proteolytically activated prodrugs of Phosphoramide mustard by prostate-specific antigen (PSA), a series of tetrapeptide (Cbz-Ser-Ser-Phe-Tyr)-conjugated 4-aminocyclophosphamide (4-NH(2)-CPA) isomers were synthesized and evaluated as substrates of PSA. The cleavage of the conjugates by PSA were found to be stereoselective as only the two isomers with 4R-configuration were efficiently cleaved by PSA. The cis-(2R,4R)-isomer was the best substrate of PSA with a half-life of 12min. LC/MS analysis of the incubation solution of this isomer with PSA suggests that 4-NH(2)-CPA is released upon proteolysis and quickly degrades to cytotoxic Phosphoramide mustard. These results clarified the stereochemical requirements of PSA on the peptide conjugates of 4-NH(2)-CPA and demonstrated the potential of these conjugates as potential PSA-activated prodrugs targeting prostate cancer.
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n 2 2 dimethyl 2 2 nitrophenyl acetyl 4 aminocyclophosphamide as a potential bioreductively activated prodrug of Phosphoramide mustard
Bioorganic & Medicinal Chemistry Letters, 2008Co-Authors: Yongying JiangAbstract:N-(2,2-Dimethyl-2-(2-nitrophenyl)acetyl)-4-aminocyclophosphamide isomers (DMNA-NH-CPA, 4) were synthesized stereospecifically from Boc-L-Hse(OBn)-OH and the degradation of the corresponding reduced amine 5a was investigated by UV/vis spectroscopy and LC/MS. The rate of cyclization of 5a was found to increase with decreasing pH, with half-lives ranging from 3.2 to 54 min at pH 4-7.4, suggesting that the cyclization is catalyzed by the hydronium ions. LC/MS analysis of the degradation products of 5a indicates that 4-aminocyclophosphamide is rapidly released from 4 upon reductive activation under acidic conditions and further decomposes into the cytotoxic Phosphoramide mustard. These results validated 4-aminocyclophosphamide as a prodrug form of Phosphoramide mustard and suggest that compound 4 can potentially be used as a prodrug of Phosphoramide mustard for bioreductive activation.
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Nitroaryl Phosphoramides as novel prodrugs for E. coli nitroreductase activation in enzyme prodrug therapy.
Journal of Medicinal Chemistry, 2003Co-Authors: Yongying Jiang, Jiye Han, Patrick Browne, Peter F. Searle, Paul R. Race, Richard J. Knox, Eva I. HydeAbstract:Cyclic and acyclic nitroaryl Phosphoramide mustard analogues were activated by E. coli nitroreductase, an enzyme explored in GDEPT. The more active acyclic 4-nitrobenzyl Phosphoramide mustard (7) showed 167 500x selective cytotoxicity toward nitroreductase-expressing V79 cells with an IC(50) as low as 0.4 nM. This is about 100x more active and 27x more selective than CB1954 (1). The superior activity was attributed to its better substrate activity (k(cat)/K(m) 19x better than 1) and/or excellent cytotoxicity of Phosphoramide mustard released.
Huayin Huang - One of the best experts on this subject based on the ideXlab platform.
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chemo and enantioselective addition and β hydrogen transfer reduction of carbonyl compounds with diethylzinc reagent in one pot catalyzed by a single chiral organometallic catalyst
Journal of Organic Chemistry, 2015Co-Authors: Huayin Huang, Guangling Bian, Hua Zong, Ling SongAbstract:Using a single chiral Phosphoramide–Zn(II) complex as the catalyst, the asymmetric β-H transfer reduction of aromatic α-trifluoromethyl ketones and enantioselective addition of aromatic aldehydes with Et2Zn in one pot were successfully realized, affording the corresponding additive products of secondary alcohols in high yields (up to 99%) with excellent enantioselectivities (up to 98% ee) and the reduction products of α-trifluoromethyl alcohols in good to excellent yields with up to 77% ee.
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investigation on the asymmetric addition reactions between varied nonaromatic aldehydes and diethylzinc catalyzed by chiral Phosphoramide and thiophosphorodiamide ligands
Tetrahedron Letters, 2015Co-Authors: Huayin Huang, Guangling Bian, Hua Zong, Ling SongAbstract:The asymmetric addition reactions between varied nonaromatic aldehydes and diethylzinc catalyzed by chiral Phosphoramide L1 and thiophosphorodiamide L4 were thoroughly investigated. Both ligands worked very well for α-branched aliphatic and α-branched α,β-unsaturated aldehydes. For α-nonbranched aliphatic aldehydes, L4 behaved much better than L1. For α-nonbranched α,β-unsaturated aldehydes, L4 showed high enantioselectivities and L1 only gave racemic alcohol products.
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highly efficient asymmetric additions of diethylzinc to aldehydes triply activated by chiral Phosphoramide zn ii complexes derived from cinchona alkaloids
Chirality, 2013Co-Authors: Bin Shen, Huayin Huang, Guangling Bian, Hua Zong, Ling SongAbstract:New chiral Phosphoramide ligands derived from cinchona alkaloids were developed, which react with diethylzinc to form chiral Phosphoramide-Zn(II) complexes containing two Lewis bases and one Lewis acid. These trifunctional complexes can serve as highly efficient chiral catalysts for triple activation of enantioselective addition reactions of diethylzinc with aldehydes to give desired alcohol products with excellent yields and enantiomeric excess (ee) values up to 99%. Chirality 25:561-566, 2013. © 2013 Wiley Periodicals, Inc.
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synergistic effect of achiral quaternary ammonium salt on asymmetric additions of diethylzinc to aldehydes
Tetrahedron Letters, 2013Co-Authors: Hua Zong, Huayin Huang, Guangling Bian, Ling SongAbstract:Abstract Our investigation has shown that achiral quaternary ammonium salt has a significant synergistic effect on the asymmetric additions of diethylzinc to aldehydes catalyzed by chiral Phosphoramide–Zn(II) complex. The addition of 10 mol % NBu 4 X can dramatically reduce the loading amount of chiral ligand without sacrificing the excellent reactivity and enantioselectivity of the asymmetric reaction.