- Chiral recognition of diketopiperazine cyclo(Pro-Gly) and propranolol using (-)-Epigallocatechin-3-O-gallate
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In the 1H-NMR spectrum of a solution containing an equimolecular amount of cyclo(L-Pro-Gly), cyclo(D-Pro-Gly) and (-)-epigallocatechin-3-O-gallate (EGCg) in a D2O, a difference in the chemical shift of 1H-NMR signal for H7a, H7β8a of the Pro residue was observed. Judging from the crystal structures of the 2: 2 complexes of EGCg and cyclo(L-Pro-Gly), cyclo(D-Pro-Gly), the difference in the chemical shift resulted mainly from a magnetic anisotropic shielding effect by the ring current from the B ring of EGCg. Therefore, it was considered that chirality of cyclo(Pro-Gly) was recognized by EGCg in the D2O solution. Furthermore, in the 1H-NMR spectrum of a solution containing an equimolecular amount of racemic propranolol ((R)- and (S)-propranolols) and EGCg in D2O, the 1H-NMR signal for H2 of the naphthalene group was observed as two doublets, suggesting that the racemic propranolol formed diastereomers of complexes with EGCg; as a result, chirality of propranolol was recognized by EGCg in the D2O solution.
- Ishizu, Takashi,Tsutsumi, Hiroyuki,Yokoyama, Emi,Tanabe, Haruka,Yokoyama, Aoi
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- Molecular capture and conformational change of diketopiperazines containing proline residues by epigallocatechin-3-O-gallate in water
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The addition of an aqueous solution of diketopiperazine cyclo(Pro-Xxx) (Xxx: amino acid residue) to an aqueous solution of (?)-epigallocatechin-3-O-gallate (EGCg) led to precipitation of the complex of EGCg and cyclo(Pro-Xxx). The molecular capture abilities of cyclo(Pro-Xxx) using EGCg were evaluated by the ratio of the amount of cyclo(Pro-Xxx) included in the precipitates of the complex with EGCg to that of the total cyclo(Pro-Xxx) used. Stronger hydrophobicity of the side chain of the amino acid residue of cyclo(Pro-Xxx) led to a higher molecular capture ability. Furthermore, the molecular capture ability decreased when the side chain of the amino acid residue had a hydrophilic hydroxyl group. When diketopiperazine cyclo(Pro-Xxx), excluding cyclo(D-Pro-L-Ala), was taken into the hydrophobic space formed by the three aromatic A, B, and B′ rings of EGCg, and formed a complex, their conformation was maintained in the hydrophobic space. Based on nuclear Overhauser effect (NOE) measurement, the 3-position methyl group of cyclo(D-Pro-L-Ala) in D2O was axial, whereas that of cyclo(L-Pro-L-Ala) was equatorial. When cyclo(D-Pro-L-Ala) was taken into the hydrophobic space of EGCg and formed a 2:2 complex, its 3-position methyl group changed from the axial position to the equatorial position due to steric hindrance by EGCg.
- Ishizu, Takashi,Tokunaga, Miku,Fukuda, Moeka,Matsumoto, Mana,Goromaru, Takeshi,Takemoto, Soushi
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p. 585 - 589
(2021/06/06)
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- AGRICULTURAL CHEMICAL CONTAINING 2,5-DIKETOPIPERAZINE DERIVATIVE AS ACTIVE INGREDIENT
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Disclosed herein is an agricultural agent containing a 2,5-diketopiperazine derivative capable of controlling plant diseases and promoting plant growth or an agriculturally acceptable salt thereof as an active ingredient.
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Paragraph 0033
(2013/06/05)
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- Bis(2-sulfanylethyl)amido peptides enable native chemical ligation at proline and minimize deletion side-product formation
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Native chemical ligation of C-terminal peptidyl prolyl alkylthioesters with N-terminal cysteinyl peptides usually exhibits poor kinetic rates compared to other C-terminal amino acid residues. It is shown here that the reaction is accompanied by the formation of a deletion side product which is minimized by using a bis(2-sulfanylethyl)amido (SEA) thioester surrogate at a mildly acidic pH.
- Raibaut, Laurent,Seeberger, Phillip,Melnyk, Oleg
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supporting information
p. 5516 - 5519
(2013/11/19)
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- Direct acyl substitution of carboxylic acids: A chemoselective o- to N-acyl migration in the traceless staudinger ligation
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A chlorophosphite-modified, Staudinger-like acylation of azides involving a highly chemoselective, direct nucleophilic acyl substitution of carboxylic acids is described. The reaction provides the corresponding amides with analytical purity in 32-97 % yield after a simple aqueous workup without the need for a pre-activation step. The use of chlorophosphites as dual carboxylic acid-azide activating agents enables the formation of acyl C-N bonds in the presence of a wide range of nucleophilic and electrophilic functional groups, including amines, alcohols, amides, aldehydes, and ketones. The coupling of carboxylic acids and azides for the formation of alkyl amides, sulfonyl amides, lactams, and dipeptides is described. Copyright
- Kosal, Andrew D.,Wilson, Erin E.,Ashfeld, Brandon L.
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supporting information
p. 14444 - 14453,10
(2020/09/16)
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- Design, synthesis, and structure-activity relationship study of bicyclic piperazine analogs of indole-3-carboxamides as novel cannabinoid CB1 receptor agonists
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Bicyclic piperazine derivatives were synthesized as conformationally constrained analogs of N-alkyl piperazines and were found to be potent CB1 receptor agonists. The CB1 receptor agonist activity was dependent upon the absolute configuration of the chiral center of the bicyclic ring system. Although the conformational constraint did not protect the compounds from metabolism by N-dealkylation, several bicyclic analogs were found to be more potent than the unconstrained lead compound. Compound 8b demonstrated potent antinociceptive activity in vivo.
- Moir, Elizabeth M.,Yoshiizumi, Kazuya,Cairns, Jim,Cowley, Phillip,Ferguson, Morag,Jeremiah, Fiona,Kiyoi, Takao,Morphy, Richard,Tierney, Jason,Wishart, Grant,York, Mark,Baker, James,Cottney, Jean E.,Houghton, Andrea K.,McPhail, Petula,Osprey, Andrew,Walker, Glenn,Adam, Julia M.
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scheme or table
p. 7327 - 7330
(2011/01/12)
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- 6' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1—R4 A, B, D, E, and G are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 37
(2008/12/08)
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- Kinetics of diketopiperazine formation using model peptides
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The intramolecular aminolysis of Phe-Pro-p-nitroaniline (Phe-Pro-pNA) to Phe-Pro-diketopiperazine (Phe-Pro-DKP) was studied as a function of pH, temperature, buffer concentration, and buffer species using an HPLC assay that permits simultaneous analysis o
- Goolcharran, Chimanlall,Borchardt, Ronald T.
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p. 283 - 288
(2007/10/03)
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- Synthesis and Evaluation of Conformationally Restricted N--N-methyl-2-(1-pyrrolidinyl)ethylamines at ? Receptors. 2. Piperazines, Bicyclic Amines, Bridged Bicyclic Amines, and Miscellaneous Compounds
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As a continuation of our earlier study (J.Med.Chem. 1992, 35, 4334-4343) we conformationally restricted the ?-receptor ligand 2-(1-pyrrolidinyl)-N--N-methylethylamine (1) by incorporating it into a series of homologous piperazines 3-9 and homopiperazines 10 and 11, diazabicyclononanes and decanes, bridgehead bicyclooctanes and nonanes as well as other miscellaneous compounds. ?-Receptor binding affinites were obtained using (+)-pentazocine in guinea pig brain membrane ?1 sites.The studies suggest that the nitrogen lone pair orient ation found in the piperazines affords the strongest binding interaction.Other nitrogen lone pair orientations or compounds representing unlikely staggered conformations of 1 -1,4-diazabicyclononane (16)> show very weak ? interaction.Comperison of the binding data of different N-substituted homologues of 1 with those of the 1--4-alkylpiperazines suggests that the two nitrogen atoms of 1 are working in opposition to one another in terms of their sensitivity to steric bulk.The high binding affinity of the 1,4-diazabicyclononanes 12 suggests that these may approximate the methyl and pyrrolidine ring conformations found in 1 when it is bound to the ? receptor.Compound 12 exhibited a 4-fold enantioselectivity favoring (+)-12.The synthesis of 6,7-dichloro-2-amino>tetralin (19) and its desmethyl derivative 20 permitted constraint of the 3,4-dichlorophenyl and N-methyl moieties of 1 into a gauche orientation.The binding data suggests that this conformation in 1 favors strong binding interaction at ?-receptors. ?-Receptor K1's ra nged from 0.55 nM for 1--4-n-butylpiperazine (7) to 654 nM for 16.Overall comparison of the results indicate that 1 is subject to considerable conformational freedom and suggests that the ?-receptor is not subject to rigid stereochemical restraints with 1.These results add to our earlier study where we restrained 1 using simple monocyclic heterocycles.
- Costa, Brian R. de,He, Xiao-shu,Linders, Joannes T.M.,Dominguez, Celia,Gu, Zi Qiang,et al.
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p. 2311 - 2320
(2007/10/02)
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