55750-61-3Relevant academic research and scientific papers
Synthesis N - maleic imide-based arylalkylic and its succinyl eater of method
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, (2017/10/13)
The invention provides a method for synthesizing N-maleimidoalkyl acid and succinimido ester thereof, which comprises the following steps: (a) carrying out cyclization reaction on a compound disclosed as Formula (II) and phenyl 4-nitrotrifluoroacetate in an organic solvent in the presence of alkali to obtain N-maleimidoalkyl acid disclosed as Formula (III); and (b) reacting the N-maleimidoalkyl acid disclosed as Formula (III) and an acylation reagent in an organic solvent at reflux temperature to obtain an acyl chloride intermediate disclosed as (IV), reacting the acyl chloride intermediate disclosed as (IV) with N-hydroxy succinimide in an organic solvent in the presence of alkali to obtain the N-maleimidoalkyl acid succinimido ester disclosed as Formula (V). The method has the advantages of simple technique, high yield and high product purity, and is suitable for industrial production. The reaction route is disclosed in the specification.
Advanced aqueous-phase phosphoramidation reactions for effectively synthesizing peptide-oligonucleotide conjugates trafficked into a human cell line
Wang, Tzu-Pin,Ko, Ni Chien,Su, Yu-Chih,Wang, Eng-Chi,Severance, Scott,Hwang, Chi-Ching,Shih, Ying Ting,Wu, Min Hui,Chen, Yen-Hsu
, p. 2417 - 2433 (2013/02/23)
Peptide-oligonucleotide conjugates (POCs) have held promise as effective therapeutic agents in treating microbial infections and human genetic diseases including cancers. In clinical applications, POCs are especially useful to circumvent cellular delivery and specificity problems of oligonucleotides. We previously reported that nucleic acid phosphoramidation reactions performed in aqueous solutions have the potential for facile POC synthesis. Here, we carried out further studies to significantly improve aqueous-phase two-step phosphoramidation reaction yield. Optimized reactions were employed to effectively synthesize POCs for delivery into human A549 cells. We achieved optimization of aqueous-phase two-step phosphoramidation reaction and improved reaction yield by (1) determining appropriate co-solutes and co-solute concentrations to acquire higher reaction yields, (2) exploring a different nucleophilicity of imidazole and its derivatives to stabilize essential nucleic acid phosphorimidazolide intermediates prior to POC formation, and (3) enhancing POC synthesis by increasing reactant nucleophilicity. The advanced two-step phosphoramidation reaction was exploited to effectively conjugate a well-studied cell penetrating peptide, the Tat48-57 peptide, with oligonucleotides, bridged by either no linkers or a disulfide-containing linker, to have the corresponding POC yields of 47-75%. Phosphoramidation-synthesized POCs showed no cytotoxicity to human A549 cells at studied POC concentrations after 24 h inoculation and were successfully trafficked into the human A549 cell line as demonstrated by flow cytometry, fluorescent microscopy, and confocal laser scanning microscopy study. The current report provides insight into aqueous-phase phosphoramidation reactions, the knowledge of which was used to develop effective strategies for synthesizing POCs with crucial applications including therapeutic agents for medicine.
Synthesis of N-Maleoyl-aminoacids and -peptides
Augustin, Manfred,Mueller, Wolfgang
, p. 789 - 798 (2007/10/02)
N-Maleoyl-aminoacid-N'-hydroxysuccinimidesters 3 or N-maleoyl-aminobenzoic acids 5 are synthsized from N-maleyl-aminoacids 1 on different ways.N-maleoyl-aminobenzoic-4-nirophenyl-, -2-nitro-phenyl- or 2,4-dinitro-phenylesters 6, 7 and 8 will be obtained from 1 or 5. o-Mercaptoaniline, thiourea or cysteine react with 5 to benzothiazines 9, thiazolidines 10 and 1,4-thiazines 11.From 5 the peptides 12 are yielded.The pentapeptide 13 are formed from 12 by addition of glutathione.
Design and Synthesis of Naltrexone-Derived Affinity Labels with Nonequilibrium Opioid Agonist and Antagonist Activities. Evidence for the Existence of Different μ Receptor Subtypes in Different Tissues
Sayre, L. M.,Larson, D. L.,Takemori, A. E.,Portoghese, P. S.
, p. 1325 - 1335 (2007/10/02)
A series of β-funaltrexamine (2, β-FNA) analogues (3-14) were synthesized that contain a variety of electrophilic groups attached at the 6β-position of the opiate.The opioid agonist and antagonist activities of these ligands were evaluated in the guinea pig ileum (GPI) and mouse vas deferens (MVD) in vitro assays.Several of the compounds behaved like β-FNA in that they exhibited reversible agonist activity at κ opioid receptors and irreversible antagonist activity at μ opioid receptors.The rank order of irreversible antagonism for a series of related Michael acceptors did not parallel their intrinsic chemical reactivity, confirming that the degree of covalent binding is in part dependent on the spatial disposition of the electrophilic center relative to the receptor nucleophile (secondary recognition).The maleimidoacetamide 8 behaved very differently from β-FNA in that it exhibited considerably greater irreversible μ antagonism in MVD relative to the μ blockage in the GPI.This suggests that different proportions of μ receptor subtypes exist in the two tissues.Several of the agents tested, including some nonreactive control compounds, displayed an unusual type of persistent κ agonist activity in the GPI.This activity, which was reversed by addition of naxolone, reappeared upon washing.Receptor models have been presented to explain this effect.A few of the reactive ligands displayed a true nonreversible κ agonist activity, suggesting a covalent association with the receptor.Of note in this regard was the propiolamide 6, which appeared to be an irreversible mixed agonist-antagonist at κ and μ receptors.
