2666-93-5Relevant articles and documents
A convenient protocol for selective cleavage of 2-hydroxy acid amides. Application to semisynthesis of the cyclic heptapeptide aza HUN-7293.
Schreiner, Erwin P,Kern, Michael,Steck, Andrea
, p. 8299 - 8304 (2002)
A two-step protocol for the first chemoselective cleavage of 2-hydroxy acid amides has been developed. Mesylation of the model substrate 2-(hydroxypropionylamino)-4-methylpentanoic acid methyl ester (11) followed by treatment with N-ethylthiourea (13) all
Structure and biosynthesis of chrysophysarin A, a plasmodial pigment from the slime mould Physarum polycephalum (Myxomycetes)
Eisenbarth, Sophie,Steffan, Bert
, p. 363 - 365 (2000)
A yellow optically-active pigment, chrysophysarin A (1), has been isolated from microplasmodia of the slime mould Physarum polycephalum. The structure was established by means of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration
New amino acid clubbed Schiff bases inhibit carbonic anhydrase II, α-glucosidase, and urease enzymes: in silico and in vitro
Al-Harrasi, Ahmed,Al-Yahyaei, Balqees Essa Mohammad,Csuk, Rene,Halim, Sobia Ahsan,Khan, Ajmal,Khan, Majid,Khiat, Mohammed,Muhammed, Niaz,Rafiq, Kashif,Shah, Zarbad,Ur Rehman, Najeeb
, p. 712 - 728 (2021/01/18)
Combating pathological conditions related to hyperactivity of enzymes remains a formidable challenge for health. Small molecules therapy constitutes one of the means to circumvent the medical disorders resulting from enzyme hyperactivity. In this regard, we have synthesized structurally diverse amino acid hybrid Schiff bases (5a–5l and 10a–10k) and evaluated them for carbonic anhydrase II, α-glucosidase, and urease inhibitory potential. These new chemical scaffolds showed variable efficacies against the selected enzymes. The results indicated that compounds 5b (11.8 ± 1.33 μM), 10i (83.3 ± 1.13 μM), and 10f (88.2 ± 2.27 μM) are the most active scaffolds against carbonic anhydrase II, α-glucosidase, and urease, respectively. A structure–activity relationship revealed the most structural features contributing to the overall activities. Molecular docking suggested that these compounds possess excellent binding interactions with the active site residues of the targets by interacting through hydrogen bonding, π–π, and π–cation interactions.
Continuous flow heterogeneous catalytic reductive aminations under aqueous micellar conditions enabled by an oscillatory plug flow reactor
?tv?s, Sándor B.,Buchholcz, Balázs,Darvas, Ferenc,Kappe, C. Oliver,Novák, Zoltán,Sipos, Gellért,Wernik, Michaela
supporting information, p. 5625 - 5632 (2021/08/16)
Despite the fact that continuous flow processing exhibits well-established technical advances, aqueous micellar chemistry, a field that has proven extremely useful in shifting organic synthesis to sustainable water-based media, has mostly been explored under conventional batch-based conditions. This is particularly because of the fact that the reliable handling of slurries and suspensions in flow has been considered as a significant technical challenge. Herein, we demonstrate that the strategic application of an oscillatory plug flow reactor enables heterogeneous catalytic reductive aminations in aqueous micellar media enhancing mass transport and facilitating process simplicity, stability and scalability. The micellar flow process enabled a broad range of substrates, including amino acid derivatives, to be successfully transformed under reasonably mild conditions utilizing only very low amounts of Pd/C as a readily available heterogeneous catalyst. The preparative capabilities of the process along with the recyclability of the heterogenous catalyst and the aqueous reaction media were also demonstrated. This journal is
Total Synthesis of the Natural Herbicide MBH-001 and Analogues
Barber, David M.,D?ller, Uwe,Dietrich, Hansj?rg,Hoffmann, Michael G.,Kocakaya, Tamer,Kuhn, Birgit,Maier, Martin E.,Morkunas, Marius,Schmutzler, Dirk,Schnatterer, Stefan
, p. 2271 - 2290 (2020/04/23)
The first total synthesis of the natural herbicide MBH-001 (1) is reported. Structurally it is a 2-methyloxazol-5(2H)-one with a (1-hydroxyethyl) substituent at the 2-position. By relying on cyclic nitrones, a flexible route to MBH-001 and relevant analogues was developed. Key steps include the reaction of a 2-hydroxyimino ester with an aldehyde to form a 5-oxo-2,5-dihydrooxazole 3-oxide. In an aldol-type reaction, the anion of these cyclic nitrones reacted with an aldehyde at the 2-position. A final reduction of the nitrone to the corresponding imine using zinc led to the target compounds. The cyclic nitrones are also accessible by reacting an α-keto acid with an oxime. These two versatile synthetic routes enabled us to prepare the first MBH-001 analogues for structure activity relationship analysis of the herbicidal efficacy. Thus, furthering our aim of developing new herbicides to tackle the ever-growing problem of weed resistance.
Synthesis and evaluation of antitumor activities of 4-selenopyrimidine derivatives
Shi, Mingxing,Wang, Libo,Zhang, Long,Wang, Kexin,Zhang, Hualin,Wang, Yajing,Li, Chang,Han, Weina
, p. 96 - 116 (2020/10/22)
Pyrimidine antimetabolic agents are the essential drugs in treatment of various tumors. Novel synthesis and biological evaluation of the pyrimidine derivatives incorporating selenium element and amino acid carrier as potential antitumor agents have not been tried and studied. Based on the biological significance of pyrimidine structure, these two additional elemental fragments maybe enhance the antitumor effect and reduce toxic side effects of pyrimidine agents. The aim of this paper is to synthesis a series of 4-selenopyrimidine derivatives in order to find more potent lead compounds against cancer. In this study, 12 new 4-selenopyrimidine derivatives that are unstable in acidic solutions but very stable in alkaline and neutral solutions avoiding light were synthesized, and the antitumor activities on HepG2 cell lines of these compounds were evaluated by MTT assay. The results have shown that these compounds could reduce the proliferation of HepG2 cells in a dose-dependent fashion, and the inhibitory activity of compounds a6 was greater than that of positive control 5-fluorouracil (5-FU), the IC50 for a6 was 3.63 μM. In the comprehensive analysis of the structure–activity relationship, we could draw the antitumor effect of selenouracil derivatives is stronger than those of selenothymine derivatives. These results suggest that the substituent groups of selenium element and amino acid on the pyrimidine derivatives are vital for their antitumor activities on HepG2 cells.
N-Pyrazinoyl substituted amino acids as potential antimycobacterial agents-the synthesis and biological evaluation of enantiomers
Bárta, Pavel,Dole?al, Martin,Horá?ek, Ond?ej,Jand'Ourek, Ond?ej,Janou?ek, Ji?í,Juhás, Martin,Kone?ná, Klára,Ku?era, Radim,Ku?erová, Lucie,Kubí?ek, Vladimír,Kune?, Ji?í,Paterová, Pavla,Zitko, Jan
, (2020/04/09)
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, M. smegmatis, M. aurum, Staphylococcus aureus, Pseudomonas aeruginosa, and fungal strains, including Candida albicans and Aspergillus flavus. Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 μM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing l-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-d/l-Pgl-Me, MIC 1.95 μg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the d- and l-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.
SOLUTION PHASE ROUTES FOR WNT HEXAPEPTIDES
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, (2020/12/30)
The present disclosure relates generally to the field of polypeptide synthesis, and more particularly, to the solution phase synthesis of the Wnt hexapeptide Foxy-5 and protected derivatives and peptide fragments thereof.
Catalytic Mechanism Study on the 1,2- and 1,4-Transfer Hydrogenation of Ketimines and β-Enamino Esters Catalyzed by Axially Chiral Biscarboline-Based Alcohols
Dong, Mengxian,Wang, Jie,Wu, Shijie,Zhao, Yang,Ma, Yangyang,Xing, Yongfei,Cao, Fei,Li, Longfei,Li, Zhenqiu,Zhu, Huajie
supporting information, p. 4602 - 4610 (2019/08/30)
Axial N-O alcohols, which have two large carboline moieties connected to the axis were synthesized and used in catalytic enantioselective 1,2- and 1,4-transfer hydrogenations of total 26 ketimines and β-enamino esters. Excellent levels of enantioselectivity ranging from 91% to 99% were achieved by using catalyst (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. Interestingly, a mixture of (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide and (aR)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide was also able to provide high enantioselectivities up to 95% that is the same as that using pure (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. A plausible catalytic mechanism was suggested and total four kinds of transition states (TS) including almost 60 TS structures were investigated using density functional theory (DFT) with different basis sets such as 6-311G(2d,p). The predicted activation energy data are consistent with the experimental results. (Figure presented.).
Postsynthetic Modification of Phenylalanine Containing Peptides by C-H Functionalization
Terrey, Myles J.,Perry, Carole C.,Cross, Warren B.
supporting information, p. 104 - 108 (2019/01/11)
New methods for peptide modification are in high demand in drug discovery, chemical biology, and materials chemistry; methods that modify natural peptides are particularly attractive. A Pd-catalyzed, C-H functionalization protocol for the olefination of phenylalanine residues in peptides is reported, which is compatible with common amino acid protecting groups, and the scope of the styrene reaction partner is broad. Bidentate coordination of the peptide to the catalyst appears crucial for the success of the reaction.
