13726-69-7Relevant articles and documents
An Unconventional Redox Cross Claisen Condensation-Aromatization of 4-Hydroxyprolines with Ketones
Tang, Mi,Sun, Rengwei,Li, Hao,Yu, Xinhong,Wang, Wei
, p. 8419 - 8425 (2017)
Reaction of α-amino acids, particularly prolines and their derivatives with carbonyl compounds via decarboxylative redox process, is a viable strategy for synthesis of structurally diverse nitrogen centered heterocyclics. In these processes, the decarboxylation is the essential driving force for the processes. The realization of the redox process without decarboxylation may offer an opportunity to explore new reactions. Herein, we report the discovery of an unprecedented redox Claisen-type condensation aromatization cascade reaction of 4-substituted 4-hydroxyproline and its esters with unreactive ketones. We found that the use of propionic acid as a catalyst and a co-solvent can change the reaction course. The commonly observed redox decarboxylation and aldol condensation reactions are significantly minimized. Moreover, unreactive ketones can effectively participate in the Claisen condensation reaction. The new reactivity enables a redox cyclization via an unconventional Claisen-type condensation reaction of in situ formed enamine intermediates from ketone precursors with 4-substituted 4-hydroxyproline and its esters as electrophilic acylation partners. Under the reaction conditions, the cascade process proceeds highly regio- and stereoselectively to afford highly synthetically and biologically valued cis-2,3-dihydro-1H-pyrrolizin-1-ones with a broad substrate scope in efficient 'one-pot' operation, whereas such structures generally require multiple steps.
The selective O-acylation of hydroxyproline as a convenient method for the large-scale preparation of novel proline polymers and amphiphiles
Kristensen, Tor E.,Hansen, Finn K.,Hansen, Tore
, p. 387 - 395 (2009)
In this work we show how a direct O-acylation of trans-4-hydroxy-L-proline with acyl chlorides in trifluoroacetic acid makes a range of novel proline derivatives readily available on large-scale. No protecting groups or chromatographic techniques are involved in any of the procedures, and certain amphiphilic proline derivatives, which recently have received interest in synthesis, are now potentially some of the most readily accessible organocatalysts. The selective acylation was also utilized in the synthesis of a novel high-load proline polymer, poly(O-acryloyl-trans-4-hydroxy-L-proline), a polymer with the highest proline loading reported and for which classical methods failed for its preparation. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.
β-L-Arabinofuranosylation Conducted by 5-O-(2-pyridinecarbonyl)-L-arabinofuranosyl Trichloroacetimidate
Li, Hong-Zhan,Ding, Jie,Cheng, Chun-Ru,Chen, Yue,Liang, Xing-Yong
, p. 1 - 7 (2018)
We describe a β-L-arabinofuranosylation method by employing the 5-O-(2-pyridinecarbonyl)-L-arabinofuranosyl trichloroacetimidate 10 as a donor. This approach allows a wide range of acceptor substrates, especially amino acid acceptors, to be used. Stereoselective synthesis of β-(1,4)-L-arabinofuranosyl-(2S, 4R)-4-hydroxy-L-proline (β-L-Araf-L-Hyp4) and its dimer is achieved readily by this method. Both the stereoselectivities and yields of the reactions are excellent. To demonstrate the utility of this methodology, the preparation of a trisaccharide in a one-pot manner was carried out.
L-proline-grafted mesoporous silica with alternating hydrophobic and hydrophilic blocks to promote direct asymmetric aldol and Knoevenagel-Michael cascade reactions
An, Zhe,Guo, Ying,Zhao, Liwei,Li, Zhi,He, Jing
, p. 2566 - 2576 (2014)
Promotion of heterogeneous asymmetric catalysis is of major interest in the asymmetric catalysis field. In this work, a novel strategy for the synthesis of l-proline-grafted mesoporous silica with alternating hydrophobic and hydrophilic blocks to promote the heterogeneous asymmetric catalysis was reported. The surface synergies in the neat environment and the interface acceleration in aqueous medium thereby fostered high catalytic activities and enantioselectivity in the direct aldol reaction and the Knoevenagel-Michael cascade reaction. The l-proline loading could be reduced to as low as 0.63 mol %, giving 95% ee for anti-isomers and 81% ee for syn-isomers in the catalytic asymmetric aldol reaction of nitrobenzaldehyde and cyclohexanone, which was hard to accomplish on the homogeneous counterpart. In the direct asymmetric aldol reaction of ethyl-2-oxoacetate and cyclohexanone, 82% yield in 24 h and 90% ee were achieved. More exciting, the catalysts were applied to more exigent reactions. As an example, in the Knoevenagel-Michael cascade reaction, 85% yield in 10 h and up to 91% ee was achieved.
Chemical Probes Unravel an Antimicrobial Defense Response Triggered by Binding of the Human Opioid Dynorphin to a Bacterial Sensor Kinase
Wright, Megan H.,Fetzer, Christian,Sieber, Stephan A.
, p. 6152 - 6159 (2017)
Host-microbe communication via small molecule signals is important for both symbiotic and pathogenic relationships, but is often poorly understood at the molecular level. Under conditions of host stress, levels of the human opioid peptide dynorphin are elevated, triggering virulence in the opportunistic pathogenic bacterium Pseudomonas aeruginosa via an unknown pathway. Here we apply a multilayered chemical biology strategy to unravel the mode of action of this putative interkingdom signal. We designed and applied dynorphin-inspired photoaffinity probes to reveal the protein targets of the peptide in live bacteria via chemical proteomics. ParS, a largely uncharacterized membrane sensor of a two-component system, was identified as the most promising hit. Subsequent full proteome studies revealed that dynorphin(1-13) induces an antimicrobial peptide-like response in Pseudomonas, with specific upregulation of membrane defense mechanisms. No such response was observed in a parS mutant, which was more susceptible to dynorphin-induced toxicity. Thus, P. aeruginosa exploits the ParS sensing machinery to defend itself against the host in response to dynorphin as a signal. This study highlights interkingdom communication as a potential essential strategy not only for induction of P. aeruginosa virulence but also for maintaining viability in the hostile environment of the host.
Rational Drug Design of Topically Administered Caspase 1 Inhibitors for the Treatment of Inflammatory Acne
Fournier, Jean-Fran?ois,Clary, Laurence,Chambon, Sandrine,Dumais, Laurence,Harris, Craig Steven,Millois, Corinne,Pierre, Romain,Talano, Sandrine,Thoreau, étienne,Aubert, Jérome,Aurelly, Michèle,Bouix-Peter, Claire,Brethon, Anne,Chantalat, Laurent,Christin, Olivier,Comino, Catherine,El-Bazbouz, Ghizlane,Ghilini, Anne-Laurence,Isabet, Tatiana,Lardy, Claude,Luzy, Anne-Pascale,Mathieu, Céline,Mebrouk, Kenny,Orfila, Danielle,Pascau, Jonathan,Reverse, Kevin,Roche, Didier,Rodeschini, Vincent,Hennequin, Laurent Fran?ois
, p. 4030 - 4051 (2018)
The use of an interleukin β antibody is currently being investigated in the clinic for the treatment of acne, a dermatological disorder affecting 650M persons globally. Inhibiting the protease responsible for the cleavage of inactive pro-IL1β into active IL-1β, caspase-1, could be an alternative small molecule approach. This report describes the discovery of uracil 20, a potent (38 nM in THP1 cells assay) caspase-1 inhibitor for the topical treatment of inflammatory acne. The uracil series was designed according to a published caspase-1 pharmacophore model involving a reactive warhead in P1 for covalent reversible inhibition and an aryl moiety in P4 for selectivity against the apoptotic caspases. Reversibility was assessed in an enzymatic dilution assay or by using different substrate concentrations. In addition to classical structure-activity-relationship exploration, topical administration challenges such as phototoxicity, organic and aqueous solubility, chemical stability in solution, and skin metabolic stability are discussed and successfully resolved.
Synthesis and DNA binding property of a novel peptide nucleic acid that contains cis-4-adeninyl-L-prolinol unit
Shigeyasu, Masanori,Kuwahara, Masayasu,Sisido, Masahiko,Ishikawa, Teruhiko
, p. 634 - 635 (2001)
A novel oxy-peptide nucleic acid that contains a cis-4-adeninyl-L-prolinol unit in the main chain (PPNA) was synthesized. The peptide nucleic acid with nine adenine units [PPNA(A9)] hybridized with the complementary DNA (T9). The hybrid showed a very sharp melting curve with Tm = 34 °C.
Synthetic Marine Sponge Collagen by Late-Stage Dihydroxylation
Priem, Christoph,Geyer, Armin
, p. 162 - 165 (2018)
Based on the observation that an increased substrate size is paralleled by an enhanced diastereoselectivity, a late-stage dihydroxylation protocol toward the 21mer CMP (collagen model peptide) Ac-(Pro-Hyp-Gly)3-Pro-Dyp-Gly-(Pro-Hyp-Gly)3-NH2 is presented. C3 and C4 hydroxylation have a converse effect on the triple-helical stability of collagen. Their combined influence on the melting temperature was studied by NMR spectroscopy.
The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase
Pi?ha, Jan,Vaňek, Václav,Budě??sińsky, Milo?,Mlad?ková, Jana,Garrow, Timothy A.,Ji??acek, Ji??i
, p. 256 - 275 (2013)
Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely defi ne the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine.
Collagen labelling with an azide-proline chemical reporter in live cells
Amgarten, Beatrice,Rajan, Rakesh,Martínez-Sáez, Nuria,Oliveira, Bruno L.,Albuquerque, Inês S.,Brooks, Roger A.,Reid, David G.,Duer, Melinda J.,Bernardes, Gon?alo J. L.
, p. 5250 - 5252 (2015)
We have developed a strategy for selective imaging of collagen in live foetal ovine osteoblasts. Our approach involves the incorporation of an azide-tagged proline in the biosynthesis of collagen followed by labelling using a strain-promoted [3+2] azide-alkyne cycloaddition reaction. This journal is
