- Transition Metal-Free N-Arylation of Amino Acid Esters with Diaryliodonium Salts
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A transition metal-free approach for the N-arylation of amino acid derivatives has been developed. Key to this method is the use of unsymmetric diaryliodonium salts with anisyl ligands, which proved important to obtain high chemoselectivity and yields. The scope includes the transfer of both electron deficient, electron rich and sterically hindered aryl groups with a variety of different functional groups. Furthermore, a cyclic diaryliodonium salt was successfully employed in the arylation. The N-arylated products were obtained with retained enantiomeric excess.
- Kervefors, Gabriella,Kersting, Leonard,Olofsson, Berit
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supporting information
p. 5790 - 5795
(2021/03/08)
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- Highly enantioselective enzymatic resolution of aromatic β-amino acid amides with Pd-catalyzed racemization
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The kinetic resolution of an aromatic β-amino acid amide 3a-d via N-acylation was explored with two lipases, Candida antarctica lipase A (CALA) and Pseudomonas stutzeri lipase (PSL). The PSL-catalyzed resolution proceeded with excellent enantioselectivity
- Kim, Mahn-Joo,Choi, Eunjeong,Kim, Yunwoong,Ahn, Yangsoo,Park, Jaiwook
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p. 1449 - 1452
(2013/12/04)
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- Synthesis, in vitro and in vivo biological evaluation, docking studies, and structure-activity relationship (SAR) discussion of dipeptidyl boronic acid proteasome inhibitors composed of β-amino acids
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A series of novel dipeptidyl boronic acid proteasome inhibitors composed of β-amino acids were synthesized, in vitro and in vivo biologically evaluated, and theoretically modeled for the first time. From the screened racemic compounds in enzyme, 4i was the most active. The IC50 value of its pure enantiomer 4q was 9.6 nM, 36-fold more active than its isomer 4p and as active as the marketed bortezomib in inhibiting human 20S proteasome. This candidate also showed good activities with IC50 values nearly less than 5 μM against several human solid and hematologic tumor cell lines. Safety evaluation in vivo with zebrafish and Sprague-Dawley (SD) rats showed that the candidate 4q was less toxic than bortezomib. Pharmacokinetic profiles suggested candidate 4q showed a more plasma exposure and longer half-life than bortezomib. Docking results indicated that 4q nearly interacted with 20S proteasome in a similar way as bortezomib.
- Zhu, Yongqiang,Zhu, Xinrong,Wu, Gang,Ma, Yuheng,Li, Yuejie,Zhao, Xin,Yuan, Yunxia,Yang, Jie,Yu, Sen,Shao, Feng,Li, Runtao,Ke, Yanrong,Lu, Aijun,Liu, Zhenming,Zhang, Liangren
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supporting information; experimental part
p. 1990 - 1999
(2010/08/03)
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- BETA-AMINO ACID DERIVATIVES FOR TREATMENT OF DIABETES
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Novel heterocyclic compounds of the Formula (I) in which R1, R2, R2', R2', R3, R4, R5, R6, R7 and R8 have the meanings indicated in Claim 1, are activators of glucokinase and can be used for the prevention and/or treatment of Diabetes Typ 1 and 2, obesity, neuropathy and/or nephropathy.
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Page/Page column 43
(2009/09/05)
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- β-amino acids to piperidinones by petasis methylenation and acid-induced cyclization
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(Chemical Equation Presented) Ester-imine derivatives of β-amino acids were methylenated with dimethyltitanocene under microwave irradiation and the resulting enol ethers cyclized with Broensted acid or triisopropylaluminium to give 2,6-syn-disubstituted
- Adriaenssens, Louis V.,Hartley, Richard C.
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p. 10287 - 10290
(2008/04/12)
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- Synthesis and physicochemical characterization of new C-functionalized derivatives of the gadolinium(III) complex with 3,6,10-tris(carboxymethyl)-3,6, 10-triazadodecanedioic acid (H5ttda) exhibiting fast water exchange - Potential paramagnetic reporters for molecular imaging
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To confirm the observation that [Gd(ttda)] derivatives have a significantly shorter residence time τM of the coordinated H2O molecule than [Gd(dtpa)], four new C-functionalized [Gd(ttda)] complexes, [Gd(4-Me-ttda)] (1), [Gd(4-Ph-ttda)] (2), [Gd(9-Me-ttda)] (3), and [Gd(9-Ph-ttda)] (4), were prepared and characterized (H5ttda = 3,6,10-tris(carboxymethyl)-3,6,10-triazadodecanedioic acid; H5dtpa = 3,6,9-tris(carboxymethyl)-3,6,9-triazaundecanedioic acid). The temperature dependence of the proton relaxivity for these complexes at 0.47 T and of the 17O transverse relaxation rate of H217O at 7.05 T confirm that the proton relaxivity is not limited by the H 2O-exchange rate. The residence time of the H2O molecules in the first coordination sphere of the gadolinium complexes at 310 K, as calculated from 17O-NMR data, is 13, 43, 2.9, and 56 ns for 1, 2, 3, and 4, respectively. At 310 K, the longitudinal relaxivity of 2 is higher than for the parent compound [Gd(ttda)] and the other complexes of the series. The stability of the new compounds was studied by transmetallation with Zn 2+ ions. All the new complexes are more stable than the parent compound [Gd(ttda)].
- Laurent, Sophie,Elst, Luce Vander,Vroman, Antoine,Muller, Robert N.
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p. 562 - 573
(2008/02/07)
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- Ruthenium-catalyzed asymmetric epoxidation of olefins using H 2O2, part I: Synthesis of new chiral N,N,N,-tridentate pybox and pyboxazine ligands and their ruthenium complexes
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The synthesis of chiral tridentate N,N,N-pyridine-2.6-bisoxazolines 3 (pyhox ligands) and N,N,N-pyridine-2.6-bisoxazines 4 (pyboxazine ligands) is described in detail. These novel ligands constitute a useful tool-box for the application in asymmetric catalysis. Compounds 3 and 4 are conveniently prepared by cyclization of enantiomerically pure α- or β-amino al cohols with dimethyl pyridine-2,6-dicarboximidate. The corresponding ruthenium complexes are efficient asymmetric epoxidation catalysts and have been prepared in good yield and fully char acterized by spectroscopic means. Four of these ruthenium complexes have been characterized by X-ray crystallography. For the first time the molecular structure of a pyboxazine complex (2,6-bis-[(4S)-4-phenyl-5,6- dihydro-4H-[1,3]oxazinyl]pyridine)(pyridine-2,6-dicarboxylate)ruthenium (S)-2aa, is presented.
- Tse, Man Kin,Bhor, Santosh,Klawonn, Markus,Anilkumar, Gopinathan,Jiao, Haijun,Doebler, Christian,Spannenberg, Anke,Magerlein, Wolfgang,Hugl, Herbert,Beller, Matthias
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p. 1855 - 1874
(2008/02/02)
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- Synthesis and antiaggregation activity of a new RGDF peptidomimetic
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A new RGDF peptidomimetic, [4-oxo-4-(pyperazin-1-yl)butyryl]glycyl-D,L-β-phenyl-β-alanine was synthesized. The arginyl mimetic used was the 4-oxo-4-(piperazin-1-yl)butanoic acid residue, and the Asp-Phe chain is replaced by a β-phenyl-β-alanine residue. The synthesized pseudopeptide showed ability to inhibite ADF-induced thrombocyte aggregation in a thrombocyte-rich rat blood plasma (IC50 8.7 × 10-9 M).
- Krys'ko,Kabanov,Polishchuk,Chugunov,Pavlovskii,Andronati,Mazepa,Kabanova,Karaseva
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p. 948 - 952
(2007/10/03)
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- Synthesis and CNS activity of new 3-amino-3-arylpropionic acid derivatives
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The synthesis of new analogues of methylphenidate and modafinil, derived from 3-amino-3-arylpropionic acids, is described. Central pharmacological properties were studied in mice.
- Renault,Guillon,Huard,Miel,Stiebing,Le Bourn,Boulouard,Dallemagne,Rault
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p. 217 - 223
(2007/10/03)
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- X-ray crystallographic study of substituted perhydropyrimidinones. Extreme changes in ring conformation
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X-ray crystal structures of 20 differently substituted perhydropyrimidin-4-ones are presented. Analysis of these data reveal a remarkable conformational sensitivity of a six-membered ring to substitution. Thus half-chair, envelope, boat, twist-boat, and intermediate conformations are found for the six-membered heterocycle, providing evidence for a relatively fiat conformational energy surface in this ring. Interpretation of the preferred conformations is advanced in terms of steric interactions among substituents and, in some cases, as the result of particular conformational (A1.3 strain, anomeric) effects.
- Ramirez-Quiros, Yara,Balderas, Margarita,Escalante, Jaime,Quintana, Delia,Gallardo, Itzell,Madrigal, Domingo,Molins, Elies,Juaristi, Eusebio
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p. 8668 - 8680
(2007/10/03)
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- Novel synthesis of 4-carboxymethyl 5-alkyl/aryl oxazolidin-2-ones by rearrangement of 2-carboxymethyl 3-alkyl/aryl N-tert-butoxycarbonyl aziridines
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(matrix presented) A two-step approach for the diastereoselective synthesis of 4-carboxymethyl 5-alkyl/aryl oxazolidin-2-ones is described, which proceeds via the intermediate formation of 2-carboxymethyl 3-alkyl/aryl N-tert-butoxycarbonyl (N-Boc) aziridines. By reaction of N-Boc β-amino methyl esters with LiHMDS and iodine, trans 2,3-disubstituted N-Boc aziridines are obtained with high stereoselectivities and yields. The final rearrangement to oxazolidin-2-ones is achieved by treatment with a catalytic amount of a Lewis acid and proceeds with high yield and complete regio- and stereoselectivity.
- Tomasini, Claudia,Vecchione, Andrea
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p. 2153 - 2156
(2008/02/09)
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- SYNTHESIS OF 6-ARYL-4-HYDROXYPIPERIDIN-2-ONES AND A POSSIBLE APPLICATION TO THE SYNTHESIS OF A NOVEL HMG-CoA REDUCTASE INHIBITOR
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A series of 6-aryl-4-hydroxypiperidin-2-ones (11a-11g) were synthesised with the key step being a Dieckmann cyclisation of the appropriate methyl 3-(ethoxycarbonylacetylamino)-3-(substituted) propionate (8a-8g) and this new synthetic route was successfully applied to the synthesis of 4-hydroxy-6-(2-phenylethyl)piperidin-2-one (11h).The application of this strategy to the synthesis of the putative HMG-CoA reductase inhibitor 6--4-hydroxypiperidin-2-one (11i) was attempted, but failed during the Dieckmann cyclisation of methyl 3-(ethoxycarbonylacetylamino)- 3-propionate (8i).An alternative synthesis of a 1:1 diastereomeric mixture of (11i) was achieved by the reductive cleavage of the isoxazoline (24) with Raney nickel.The mixture of diastereoisomers (11i) was inactive in-vitro and in-vivo (rat) against HMG-CoA reductase
- Ashton, Michael J.,Hills, Susan J.,Newton, Christopher G.,Taylor, John B.,Tondu, Sylvie C. D.
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p. 1015 - 1035
(2007/10/02)
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