15329-69-8Relevant articles and documents
"one-Pot" Aminolysis/Thiol-Maleimide End-Group Functionalization of RAFT Polymers: Identifying and Preventing Michael Addition Side Reactions
Abel, Brooks A.,McCormick, Charles L.
, p. 6193 - 6202 (2016)
We show that many of the nucleophiles (catalysts, reducing agents, amines, thiols) present during "one-pot" aminolysis/thiol-maleimide end-group functionalization of RAFT polymers can promote side reactions that substantially reduce polymer end-group functionalization efficiencies. The nucleophilic catalyst 1,8-diazabicyclo[5.4.0]undec-7-ene and the reducing agent tributylphosphine were shown to initiate anionic polymerization of N-methylmaleimide (NMM) in both polar and nonpolar solvents whereas hexylamine-initiated polymerization of NMM occurred only in high-polarity solvents. Furthermore, triethylamine-catalyzed Michael reactions of the representative thiol ethyl 2-mercaptopropionate (E2MP) and NMM in polar solvents resulted in anionic maleimide polymerization when [NMM]0 > [E2MP]0. Base-catalyzed enolate formation on the α-carbon of thiol-maleimide adducts was also shown as an alternative initiation pathway for maleimide polymerization in polar solvents. Ultimately, optimal "one-pot" reaction conditions were identified allowing for up to 99% maleimide end-group functionalization of dithiobenzoate-terminated poly(N,N-dimethylacrylamide). Much of the work described herein can also be used to ensure near-quantitative conversion of small molecule thiol-maleimide reactions while preventing previously unforeseen side reactions.
Triethylamine-catalyzed synthesis of oxazepine from maleamic acids
Badru, Rahul,Singh, Baldev
, p. 635 - 640 (2015)
2-Thioxo-1,3-oxazepine-4,7-dione compounds were obtained via triethylamine-catalyzed condensation of maleamic acids with thiophosgene under anhydrous conditions. This method features relatively a simple methodology, use of inexpensive reagents, convenient operating conditions and high yields.
Thermally Sensitive Protecting Groups for Cysteine, and Manufacture and Use Thereof
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Paragraph 0085, (2021/02/12)
In a preferred embodiment, there is provided a protecting group for protecting the thiol side chain of a cysteine residue, the protecting group comprising a Diels-Alder cycloadduct of a furan and a maleimide, and optionally, a linker interposed between the thiol side chain and the Diels-Alder cycloadduct.
Dichloro Butenediamides as Irreversible Site-Selective Protein Conjugation Reagent
Abegg, Daniel,Adibekian, Alexander,Afonso, Cláudia F.,Bernardes, Gon?alo J. L.,Corzana, Francisco,Laserna, Victor,Martin, Esther M.,Ravn, Peter
supporting information, p. 23750 - 23755 (2021/10/01)
We describe maleic-acid derivatives as robust cysteine-selective reagents for protein labelling with comparable kinetics and superior stability relative to maleimides. Diamide and amido-ester derivatives proved to be efficient protein-labelling species with a common mechanism in which a spontaneous cyclization occurs upon addition to cysteine. Introduction of chlorine atoms in their structures triggers ring hydrolysis or further conjugation with adjacent residues, which results in conjugates that are completely resistant to retro-Michael reactions in the presence of biological thiols and human plasma. By controlling the microenvironment of the reactive site, we can control selectivity towards the hydrolytic pathway, forming homogeneous conjugates. The method is applicable to several scaffolds and enables conjugation of different payloads. The synthetic accessibility of these reagents and the mild conditions required for fast and complete conjugation together with the superior stability of the conjugates make this strategy an important alternative to maleimides in bioconjugation.
Synthesis and biological evaluation of novel benzylidene-succinimide derivatives as noncytotoxic antiangiogenic inhibitors with anticolorectal cancer activity in vivo
Luo, Kaixiu,Bao, Yafeng,Liu, Feifei,Xiao, Chuanfan,Li, Ke,Zhang, Conghai,Huang, Rong,Lin, Jun,Zhang, Jihong,Jin, Yi
, p. 805 - 827 (2019/07/10)
A novel series of benzylidene-succinimide derivatives were synthesized, characterized and evaluated for their cytotoxicities against HCT116, and SW480 cancer cells and NCM460 normal human cells. Their antiangiogenic capabilities were evaluated using a chick chorioallantoic membrane (CAM) assay. The compound, XCF-37b, was selected as the most potent antiangiogenic inhibitor with noncytotoxicity to evaluate the pharmacological effects on human umbilical vein endothelial cells (HUVECs) and cancer cells in vivo and in vitro. The results showed that XCF-37b inhibited HT29-cell colon tumor growth in vivo, without showing cytotoxicity against the five other cancer cell lines in vitro. Experiments confirmed that XCF-37b had obvious antiangiogenic activity by HUVEC migration and invasion and rat aortic ring angiogenesis ex vivo. Mechanism studies showed that XCF-37b inhibited the AKT/mTOR and VEGFR2 signaling pathways, as evidenced by decreased expressions of phosphor-AKT (p-AKT), p-mTOR, p-VEGFR2 (Tyr175), p-Src (Tyr416), p-FAK (Tyr925), and p-Erk1/2 (Thr202/Tyr204). Moreover, XCF-37b significantly decreased the protein expressions of matrix metalloproteinase-2 (MMP-2), MMP-9 and hypoxia-inducible factor-1α (HIF-1α). XCF-37b generally regulated angiogenic inhibition through several regulatory pathways, without significantly interfering with colorectal cancer cell growth.
1, 3-Dipolar cycloaddition reactions: Synthesis of 5-benzyl-1-(2',4'- dibromophenyl)-3-(4''-substituted phenyl)-3a,4,6,6a-tetrahydro-1H, 5H-pyrrolo[3,4-c]pyrazole-4,6-dione derivatives
Kaur, Manpreet,Singh, Baldev,Singh, Baljit
, p. 1529 - 1534 (2014/04/03)
1,3-Dipolar cycloaddition of nitrilimines 3 with N-benzyl maleimide 4 has provided 5-benzyl-1-(2',4'-dibromophenyl)-3-(4''-substituted phenyl)-3a,4,6,6a-tetrahydro-1H,5H-pyrrolo[3,4-c]pyrazole-4,6-dione derivatives 5 in excellent yield as the only isomer through a concerted pathway. Indian Academy of Sciences.
Antifungal, cytotoxic and SAR studies of a series of N-alkyl, N-aryl and N-alkylphenyl-1,4-pyrrolediones and related compounds
Sortino,Garibotto,Cechinel Filho,Gupta,Enriz,Zacchino
experimental part, p. 2823 - 2834 (2011/06/21)
The synthesis, in vitro evaluation and SAR studies of 67 maleimides and derivatives acting as antifungal agents are reported. A detailed SAR study supported by theoretical calculations led us to determine that: an intact maleimido ring appears to be necessary for a strong antifungal activity, dissimilarly affected by the substituents in positions 2 and 3. The best activities were shown by 2,3-nonsubstituted followed by 2,3 dichloro- and 2-methyl-substituted maleimides. They all were fungicide rather than fungistatic enhancing the importance of their antifungal activity. 2,3-Dimethyl and 2,3-diphenyl-maleimides possessed marginal or null activity. The presence of a flexible connecting chain in N-phenylalkyl maleimides appears not to be essential for antifungal activity, although its length shows a correlation with the antifungal behavior, displaying maleimides with alkyl chains of n = 3 and n = 4 the best antifungal activities in most fungi. Different substituents on the benzene ring did not have a clear influence on the activity. Values of chemical potential properties as well as of energy do not sufficiently discriminate between active and inactive compounds. Nevertheless, it was found that, although log P alone is not strong enough to properly predict the antifungal activity, the comparison of its values for compounds within the same sub-type, showed an enhancement of antifungal activity along with an increment of lipophilicity. In addition, the LUMO's electronic clouds of the highly active compounds showed to be concentrated on the imido ring, indicating that their carbon atoms are potential sites for nucleophilic attack. Same results were obtained from MEPs. Most of the active compounds did not show cytotoxic activity against human cancer cell lines and no one possessed hemolytic activity, indicating that their activity is selective to pathogenic fungi and that they are not toxic at MIC concentrations.
Terification of maleamic acids without double bond isomerization
Sanchez, Albert,Pedroso, Enrique,Grandas, Anna
experimental part, p. 2600 - 2606 (2010/09/07)
Activation of the carboxylic acid group of a maleamic acid by treatment with an arenesulfonyl chloride followed by addition of an alcohol affords a fumaramate or a maleamate, depending on the reaction conditions. The E isomer is obtained when the acid is treated with nearly equimolar amounts of 2,4,6-triisopropylbenzenesulfonyl chloride and an alcohol in pyridine. Replacement of pyridine by 2-picoline and use of a larger excess of activating agent (mesitylenesulfonyl chloride) and alcohol affords the Z isomer. In both cases, high diastereomeric excesses and yields are achieved.
Manganese catalyzed cis-dihydroxylation of electron deficient alkenes with H2O2
Saisaha, Pattama,Pijper, Dirk,Van Summeren, Ruben P.,Hoen, Rob,Smit, Christian,De Boer, Johannes W.,Hage, Ronald,Alsters, Paul L.,Feringa, Ben L.,Browne, Wesley R.
supporting information; experimental part, p. 4444 - 4450 (2010/11/05)
A practical method for the multigram scale selective cis-dihydroxylation of electron deficient alkenes such as diethyl fumarate and N-alkyl and N-aryl-maleimides using H2O2 is described. High turnovers (>1000) can be achieved with this efficient manganese based catalyst system, prepared in situ from a manganese salt, pyridine-2-carboxylic acid, a ketone and a base, under ambient conditions. Under optimized conditions, for diethyl fumarate at least 1000 turnovers could be achieved with only 1.5 equiv. of H2O2 with d/l-diethyl tartrate (cis-diol product) as the sole product. For electron rich alkenes, such as cis-cyclooctene, this catalyst provides for efficient epoxidation.
Synthesis of an amino moiety in trovafloxacin by using an in-expensive amidine base, N, N-diethylacetamidine
Madhusudhan,Balraju,Rajesh,Narayana, B. Venkata,Reddy
experimental part, p. 569 - 573 (2009/12/06)
The simple and in-expensive amidine base, N.N-diethylacetamidine, has been prepared and utilized in the construction of bicyclic hetero compound, 4 and employed for further reduction of amidic carbonyl groups of 4 by using NaBH 4I2-THF condition which is an efficient and commercially viable method to prepare 5 towards the synthesis of amino moiety I, in Trovafloxacin 2 an antibacterial agent.
