- A convenient protocol for selective cleavage of 2-hydroxy acid amides. Application to semisynthesis of the cyclic heptapeptide aza HUN-7293.
-
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
- Schreiner, Erwin P,Kern, Michael,Steck, Andrea
-
-
Read Online
- Structure and biosynthesis of chrysophysarin A, a plasmodial pigment from the slime mould Physarum polycephalum (Myxomycetes)
-
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
- Eisenbarth, Sophie,Steffan, Bert
-
-
Read Online
- New amino acid clubbed Schiff bases inhibit carbonic anhydrase II, α-glucosidase, and urease enzymes: in silico and in vitro
-
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.
- 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)
-
- Continuous flow heterogeneous catalytic reductive aminations under aqueous micellar conditions enabled by an oscillatory plug flow reactor
-
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
- ?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)
-
- Total Synthesis of the Natural Herbicide MBH-001 and Analogues
-
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.
- 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)
-
- Synthesis and evaluation of antitumor activities of 4-selenopyrimidine derivatives
-
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.
- Shi, Mingxing,Wang, Libo,Zhang, Long,Wang, Kexin,Zhang, Hualin,Wang, Yajing,Li, Chang,Han, Weina
-
-
- N-Pyrazinoyl substituted amino acids as potential antimycobacterial agents-the synthesis and biological evaluation of enantiomers
-
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.
- 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
-
-
- SOLUTION PHASE ROUTES FOR WNT HEXAPEPTIDES
-
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.
- -
-
Page/Page column 24
(2020/12/30)
-
- 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
-
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.).
- 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)
-
- Postsynthetic Modification of Phenylalanine Containing Peptides by C-H Functionalization
-
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.
- Terrey, Myles J.,Perry, Carole C.,Cross, Warren B.
-
supporting information
p. 104 - 108
(2019/01/11)
-
- Exciton-Coupled Circular Dichroism Characterization of Monotopically Binding Guests in Host?Guest Complexes with a Bis(zinc porphyrin) Tweezer
-
A stiff-stilbene-linked bisporphyrin tweezer with inherent helicity was used for exciton-coupled circular dichroism (ECCD) characterization of a series of monotopically binding amine guest molecules. CD signals were observed for a variety of monoamines at relatively low tweezer/amine (host/guest) ratios between 1 : 10 to 1 : 70. For the amines producing the most intense CD signals, a binding stoichiometry of 1 : 2 was found. A likely explanation is the presence of guest-guest interactions in the complexes. This is supported by the correlation observed between CD signal intensity and magnitude of possible noncovalent binding between the guests, which can be divided into three groups showing no, moderate and strong response, respectively. Further support for this rationalization comes from molecular modelling.
- Olsson, Sandra,Sch?fer, Clara,Blom, Magnus,Gogoll, Adolf
-
p. 1169 - 1178
(2019/01/04)
-
- The reactions of α-amino acids and α-amino acid esters with high valent transition metal halides: synthesis of coordination complexes, activation processes and stabilization of α-ammonium acylchloride cations
-
Titanium tetrachloride smoothly reacted with a selection of α-amino acids (aaH) in CH2Cl2 affording yellow to orange solid coordination compounds, 1a-d, in 70-78% yields. The salts [NHEt3][TiCl4(aa)], 2a-b, were obtained from TiCl4/aaH/NEt3 (aa = l-phenylalanine, N,N-dimethylphenylalanine), in 60-65% yields. The complex , 3, was isolated from the reaction of l-proline with NbCl5/NHiPr2, performed in CH2Cl2 at room temperature. The X-ray structure of 3 features a bridging (E)-1,2-bis(3,4-dihydro-2H-pyrrol-5-yl)ethene-1,2-diolate ligand, resulting from the unprecedented C-C coupling between two proline units. Unusually stable α-ammonium acyl chlorides were prepared by the reactions of PCl5/MCln (MCln = NbCl5, WCl6) with l-proline, N,N-dimethylphenylalanine, sarcosine and l-methionine. MX5 (M = Nb, Ta; X = F, Cl) reacted with l-leucine methylester and l-proline ethylester to give ionic coordination compounds, [MX4L2][MX6] (M = Nb, L = Me2CHCH2CH(NH2)CO2Me, X = F, 9; Cl, 11a; M = Nb, X = Cl, , 11c; Ta, 11d), in moderate to good yields. [NbCl5(Me2CHCH2CHNH3CO2Me)][NbCl6], 12, was isolated as a co-product of the reaction of NbCl5 with l-leucine isopropylester, and crystallographically characterized. The reaction of NbCl5 with l-serine isopropylester afforded NbCl3(OCH2CHNHCO2iPr), 13, in 66% yield. The activation of the ester O-R bond was observed in the reactions of l-leucine methyl ester with NbF5 and l-proline ethyl ester with MBr5 (M = Nb, Ta), these reactions proceeding with the release of EtF and EtBr, respectively. All the metal products were characterized by analytical and spectroscopic methods, while DFT calculations were carried out in order to provide insight into the structural and mechanistic aspects.
- Biancalana, Lorenzo,Bortoluzzi, Marco,Ferretti, Eleonora,Hayatifar, Mohammad,Marchetti, Fabio,Pampaloni, Guido,Zacchini, Stefano
-
p. 10158 - 10174
(2017/02/15)
-
- SYNTHESIS OF ARYL CYCLOHEXANE CARBOXAMIDE DERIVATIVES USEFUL AS SENSATES IN CONSUMER PRODUCTS
-
Synthesis methods to produce a series of carboxamides built off of an (S)-2-amino acid backbone or an (R)-2-amino acid backbone, depending upon the desired diastereomer of the end product.
- -
-
Paragraph 0060; 0127; 0128
(2017/03/21)
-
- Polycyclic Azetidines and Pyrrolidines via Palladium-Catalyzed Intramolecular Amination of Unactivated C(sp3)-H Bonds
-
A novel strategy to construct complex polycyclic nitrogen-containing heterocycles from aliphatic amines via picolinamide-assisted palladium-catalyzed C-H bond activation reaction was reported. The reaction exhibits broad substrate scope for the synthesis of various azabicyclic scaffolds, including azetidines and tropane-class alkaloids. Application of this method to naturally occurring (-)-cis-myrtanylamine, an unprecedented type of carbon-carbon bond activation, in which the electron-pair involved initiates an intramolecular "SN2-like" displacement of a cyclopalladium-fragment from a tertiary center, is described.
- Zhao, Jie,Zhao, Xiao-Jing,Cao, Pei,Liu, Ji-Kai,Wu, Bin
-
supporting information
p. 4880 - 4883
(2017/09/23)
-
- Simple and efficient Fmoc removal in ionic liquid
-
A mild method for an efficient removal of the fluorenylmethoxycarbonyl (Fmoc) group in ionic liquid was developed. The combination of a weak base such as triethylamine and [Bmim][BF4] makes the entire system more efficient for the cleavage at room temperature of various amines and amino acid methyl esters in short reaction times. The procedure works well even in the case of N-Fmoc amino acids bearing acid-sensitive protecting groups and of N-alkylated amino acid methyl esters. The solvent-free condition provides a complementary method for Fmoc deprotection in solution phase peptide synthesis and modern organic synthesis.
- Di Gioia,Costanzo,De Nino,Maiuolo,Nardi,Olivito,Procopio
-
p. 36482 - 36491
(2017/08/02)
-
- Hydroxy-Directed Amidation of Carboxylic Acid Esters Using a Tantalum Alkoxide Catalyst
-
We describe herein a new strategy for the chemoselective synthesis of amides by using a metal-catalyzed hydroxy-directed reaction. A hydroxy group located at the β-position of an ester group promoted the activation of a carbonyl group with a tantalum alkoxide catalyst followed by amidation reactions, leading to a wide variety of β-hydroxyamides with excellent chemeselectivity. The chemoselective amidation strategy can be extended to the catalytic synthesis of dipeptide derivatives, which remains challenging research subjects in modern organic synthesis.
- Tsuji, Hiroaki,Yamamoto, Hisashi
-
supporting information
p. 14218 - 14221
(2016/11/13)
-
- A New Set of Isoreticular, Homochiral Metal-Organic Frameworks with ucp Topology
-
A new isoreticular series of metal-organic frameworks, called UHM-25 (UHM: University of Hamburg Materials), based on the copper paddle wheel motif and a novel set of homochiral linkers has been synthesized. Starting from amino acids available from the chiral pool a synthesis procedure was established that allows a straightforward, multigram scale synthesis of homochiral linkers in 4-5 steps. These linkers carry substituents that have been proven useful in stereoselective organic chemistry, such as the Evans auxiliary or chiral amino alcohols. The resulting MOFs only differ in the chiral moiety provided by the amino acid starting material. The structure of UHM-25 is composed of cuboctahedral cages of Cu2 paddle wheel motifs connected by the isophthalate moieties of the linker. These cages are linked via the bent backbone of the linker resulting in a primitive cubic arrangement, giving rise to the rare underlying (3,4)-c binodal net ucp. MOFs of the UHM-25 series show surface areas up to SBET = 1900 m2/g. Postsynthetic modification reactions with excellent conversion rates confirmed the accessibility to the chiral groups. Furthermore, UHM-25-Pro bearing a prolinol functionality was used in a self-directed, enantioselective aldol addition of acetaldehyde, demonstrating the potential of the UHM-25 series with regard to heterogeneous, stereoselective catalysis.
- Sartor, Michael,Stein, Timo,Hoffmann, Frank,Fr?ba, Michael
-
p. 519 - 528
(2016/04/05)
-
- GLYCOAMINO ACID AND USE THEREOF
-
An object of the present invention is to provide glycoamino acid as an amino acid precursor with improved properties (particularly water-solubility, stability in water, bitter taste etc.). The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a salt thereof.
- -
-
Page/Page column 6; 7
(2016/08/17)
-
- Design, synthesis of new chiral fluorine-containing β-hydroxysulfonamides from natural amino acids and study of their anti-inflammatory and analgesic activities
-
A series of new chiral fluorine-containing β-hydroxysulfonamides were conveniently synthesized in three steps, starting from natural L-amino acids, and evaluated for their anti-inflammatory and analgesic activities. The structures of these compounds were supported by FT-IR, 1H, 13C and 19F NMR, elemental analysis and HRMS. Among the tested compounds, 4c, 4g and 4h exhibited promising anti-inflammatory activity. Moreover, compound 4h showed a significant analgesic activity. The structure–activity relationships of selected compounds were discussed.
- Gloulou, Monia,Kra?em, Jamil,Jennene, Fay?al,Ghedira, Donia,Amor, Haifa Bel Haj,Lajili, Sirine,Jalleli, Emna,Ferjani, Maha,Bouraoui, Abderrahman,Kallel, Mohamed
-
p. 1497 - 1506
(2016/07/06)
-
- Synthesis, bioactivity, docking and molecular dynamics studies of furan-based peptides as 20s proteasome inhibitors
-
Proteasome inhibitors are promising compounds for a number of therapies, including cardiovascular and eye diseases, diabetes, and cancers. We previously reported a series of furanbased peptidic inhibitors with moderate potencies against the proteasome b5 subunit, hypothesizing that the C-terminal furyl ketone motif could form a covalent bond with the catalytic residue, threonine 1. In this context, we describe further optimizations of the furan-based peptides, and a series of dipeptidic and tripeptidic inhibitors were designed and synthesized, aiming at improved potency and better solubility. Most of the tripeptidic inhibitors demonstrated improved potency and selectivity as b5 subunit inhibitors in both enzymatic and cellular assays, and good antineoplastic activities in various tumor cell lines were also observed. However, no inhibitory effects were observed for the dipeptidic compounds, which led us to presume that a noncovalent binding mode is adopted. Docking studies and molecular dynamics simulations were carried out to verify this presumption, with results showing that the distance between the furyl ketone motif and Thr1 is slightly too long to form covalent bond.
- Sun, Qi,Xu, Bo,Niu, Yan,Xu, Fengrong,Liang, Lei,Wang, Chao,Yu, Jiapei,Yan, Gang,Wang, Wei,Jin, Hongwei,Xu, Ping
-
p. 498 - 510
(2015/03/18)
-
- Chiral Pyridoxal-Catalyzed Asymmetric Biomimetic Transamination of α-Keto Acids
-
A series of chiral pyridoxals 8 and 9 have been developed from commercially available pyridoxine and (S)-α,α-diarylprolinols. The pyridoxals exhibited good catalytic activity in an asymmetric transamination of α-keto acids with 2,2-diphenylglycine (7f) as the amine source to give various α-amino acids in 29-85% yields with 53-80% ee's. The current asymmetric transamination has successfully mimicked a complete biological transamination process characterized by two half-transaminations, a small chiral pyridoxal molecule acting as the catalyst, and enantioselective control.
- Shi, Limin,Tao, Chuangan,Yang, Qin,Liu, Yong Ethan,Chen, Jing,Chen, Jianfeng,Tian, Jiaxin,Liu, Feng,Li, Bo,Du, Yongling,Zhao, Baoguo
-
supporting information
p. 5784 - 5787
(2015/12/11)
-
- NOVEL COMPOUND, PHOTOSENSITIVE RESIN COMPOSITION, AND COLOR FLITER
-
The present invention relates to a novel compound, a photosensitive resin composition comprising the compound and a color filter and, more specifically, to a compound represented by chemical formula 1, a photosensitive resin composition comprising the compound, an alkali-soluble resin, a photopolymerizable compound, a photopolymerization initiator and a solvent, and a color filter manufactured by using the photosensitive resin composition.COPYRIGHT KIPO 2016
- -
-
Paragraph 0187; 0189
(2016/11/07)
-
- Design, synthesis and evaluation of novel indole derivatives as AKT inhibitors
-
Herein, we describe the discovery and synthesis of a new series of 1,2,4,7-tetra-substituted indole derivatives as novel AKT inhibitors by optimization of a weak hit methyl 4-(2-aminoethoxy)-1H-indole-2-carboxylate (1). Both representative compounds 6a and 6o exhibited the most potent inhibitory activities against AKT1, with inhibition rates of 72.5% and 78.6%, respectively, at concentrations of 10 nM. In addition, compounds 6a and 6o also potently inhibited the phosphorylation of the downstream GSK3 protein and displayed slightly better anti-proliferative activities in a prostate cancer cell line.
- Yang, Dezhi,Wang, Peng,Liu, Jianzhen,Xing, Hualu,Liu, Yang,Xie, Wencheng,Zhao, Guisen
-
p. 366 - 373
(2014/01/17)
-
- Synthesis and cytotoxicity of the proposed structure of piperazirum, its stereoisomers and analogues
-
Piperazirum, a new biologically active alkaloid isolated from Arum palaestinum Bioss, is described, starting from commercially available α-amino acids. Two synthetic strategies were developed for the synthesis of the enantiomeric pair of compounds corresponding to the proposed structure of piperazirum. The first strategy was used in the synthesis of stereoisomers, and the second one was used in generating the analogues. The compounds synthesized were screened against different cell lines to evaluate their cytotoxicity profiles. Piperazirum, its stereoisomers, and its analogues were synthesized and tested for their antiproliferative activity. Copyright
- Sudhakar, Gangarajula,Bayya, Shruthi,Reddy, Karla Janardhan,Sridhar, Balasubramanian,Sharma, Komal,Bathula, Surendar Reddy
-
p. 1253 - 1265
(2014/03/21)
-
- A rapid entry to amino acid derived diverse 3,4-dihydropyrazines and dihydro[1,2,3]triazolo[1,5-a]pyrazines through 1,3-dipolar cycloaddition
-
An efficient, general and practical synthesis of diverse 3,4-dihydropyrazines, 6,7-dihydro-[1,2,3]triazolopyrazines and 7,8-dihydro-[1,2,3]triazolodiazepines through intramolecular 1,3-dipolar cycloaddition from amino acid derived common intermediates with high yields is described. Moreover, one-pot access to optically active 3-aryl substituted 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazines in the palladium-copper co-catalytic system has also been achieved in this work. The easy substrate availability and operational simplicity make the process suitable for further exploration. This journal is the Partner Organisations 2014.
- Bera, Saurav,Panda, Gautam
-
p. 3976 - 3985
(2014/06/09)
-
- A mild removal of Fmoc group using sodium azide
-
A mild method for effectively removing the fluorenylmethoxycarbonyl (Fmoc) group using sodium azide was developed. Without base, sodium azide completely deprotected Nα-Fmoc-amino acids in hours. The solvent-dependent conditions were carefully studied and then optimized by screening different sodium azide amounts and reaction temperatures. A variety of Fmoc-protected amino acids containing residues masked with different protecting groups were efficiently and selectively deprotected by the optimized reaction. Finally, a biologically significant hexapeptide, angiotensin IV, was successfully synthesized by solid phase peptide synthesis using the developed sodium azide method for all Fmoc removals. The base-free condition provides a complement method for Fmoc deprotection in peptide chemistry and modern organic synthesis. Graphical Abstract: [Figure not available: see fulltext.]
- Chen, Chun-Chi,Rajagopal, Basker,Liu, Xuan Yu,Chen, Kuan Lin,Tyan, Yu-Chang,Lin, Fui,Lin, Po-Chiao
-
p. 367 - 374
(2014/03/21)
-
- Deprotection/reprotection of the amino group in α-amino acids and peptides. A one-pot procedure in [Bmim][BF4] ionic liquid
-
This paper presents an efficient one-pot protocol for the sequential deprotection/reprotection of the α-amino group in α-amino acid and dipeptide methyl esters. [Bmim][BF4] is used as the solvent in the entire process. In particular, the use of the ionic liquid allows for rapid and clean removal of the 4-nitrobenzenesulfonyl (nosyl) group and for facile subsequent tert-butyloxycarbonylation of the free α-amino function under very mild conditions. N-Boc-α-amino acid as well as peptide derivatives are isolated in excellent yields, and do not require any further purification. Absolute configurations of the precursors are totally preserved during the process.
- Di Gioia,Barattucci,Bonaccorsi,Leggio,Minuti,Romio,Temperini,Siciliano
-
p. 2678 - 2686
(2014/01/06)
-
- In situ deprotection and incorporation of unnatural amino acids during cell-free protein synthesis
-
The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis removes a wide range of α-amino acid protecting groups by cleaving α-carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl and adamantyl carboxamides; α-amino form-, acet-, trifluoroacet-, and benzamides and sidechain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions. This approach allows the deprotection of amino acids to be carried out in situ to avoid separate processing steps. The advantages of this approach are demonstrated by the efficient incorporation of the chemically intractable (S)-4-fluoroleucine, (S)-4,5- dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide, (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These results also show that the fluoroand dehydroleucine and the chlorovaline are incorporated into a protein by the normal biosynthetic machinery as substitutes for leucine and isoleucine, respectively. Copyright
- Arthur, Isaac N.,Hennessy, James E.,Padmakshan, Dharshana,Stigers, Dannon J.,Lesturgez, Stéphanie,Fraser, Samuel A.,Liutkus, Mantas,Otting, Gottfried,Oakeshott, John G.,Easton, Christopher J.
-
supporting information
p. 6824 - 6830
(2013/06/26)
-
- Synthesis of peptides employing protected-amino acid halides mediated by commercial anion exchange resin
-
Coupling of protected-amino acid halides (chloride, fluoride) mediated by commercial anion exchange resin for the solution phase synthesis of peptides is described. The reaction was carried out in an organic medium, circumventing the use of an organic base or an inorganic base. The coupling is fast, clean and racemization free. The anion exchange resin functions as a solid-phase basic scavenger, soaking up the HCl produced and allowing the amine to react. The method is extended for the coupling of sterically hindered α,α,- dialkylamino acids. Graphical Abstract: [Figure not available: see fulltext.]
- Bhaskara Redddy,Kumari, Y. Bharathi,Ananda, Kuppanna
-
p. 225 - 229
(2013/12/04)
-
- Se -(9-fluorenylmethyl) selenoesters; Preparation, reactivity, and use as convenient synthons for selenoacids
-
Se-(9-Fluorenylmethyl) selenoesters are readily prepared, stable precursors to selenocarboxylates, which they liberate on treatment with DBU. Fm selenoesters are compatible with the use of TFA for the removal of Boc groups and with simple peptide bond for
- Fecourt, Fabien,Delpech, Bernard,Melnyk, Oleg,Crich, David
-
supporting information
p. 3758 - 3761
(2013/08/23)
-
- HR-MALDI-MS imaging assisted screening of β-Carboline alkaloids discovered from mycena metata
-
Fruiting bodies of Mycena metata were screened for the presence of new secondary metabolites by means of HPLC-UV, LC-HR-ESIMS, and high-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (HRMALDI- MS imaging). Thus, a new β-carboline alkaloid, 6-hydroxymetatacarboline D (1d), was isolated from fruiting bodies of M. metata. 6-Hydroxymetatacarboline D consists of a highly substituted β-carboline skeleton, which is likely to be derived biosynthetically from L-tryptophan, 2-oxoglutaric acid, L-threonine, and L-proline. The structure of the alkaloid was established by 2D NMR spectroscopic methods and HR-ESIMS. Moreover, by extensive application of LC-HR-ESIMS, LC-HR-ESIMS/MS, and LC-HR-ESIMS3 techniques we were able to elucidate the structures of a number of accompanying β-carboline alkaloids, 1a- 1c, 1e-1i, and 2a-2g, structurally closely related to 6-hydroxymetatacarboline D, which are present in M. metata in minor amounts. The absolute configuration of the stereogenic centers of the β-carboline alkaloids was determined by GC-MS comparison with authentic synthetic samples after hydrolytic cleavage and derivatization of the resulting amino acids.
- Jaeger, Robert J. R.,Lamshoeft, Marc,Gottfried, Sebastian,Spiteller, Michael,Spiteller, Peter
-
p. 127 - 134
(2013/06/27)
-
- I2-mediated diversity oriented diastereoselective synthesis of amino acid derived trans-2,5-disubstituted morpholines, piperazines, and thiomorpholines
-
Diastereoselective trans-2,5-disubstituted amino acids derived diverse morpholines, piperazines and thiomorpholines were prepared in 30 min-1 h with high yields through iodine-mediated 6-exotrig type cyclization from a single common synthetic intermediate. The displacement of iodine with hydride ion gave a methyl substituent at the 2-position of morpholines which provides an additional opportunity for diversity oriented nucleophilic substitution on the rings as well as incorporation of substituents at the 5-position from amino acids constituents.
- Bera, Saurav,Panda, Gautam
-
scheme or table
p. 1 - 4
(2012/02/16)
-
- Sandwich structure of a ruthenium porphyrin and an amino acid hydrazide for probing molecular chirality by circular dichroism
-
Owing to the strong Lewis acidity of ruthenium porphyrins, a commercial carbonyl ruthenium porphyrin and an amino acid hydrazide can assemble into a sandwich structure. The nature of such a structure is diagnostic of the absolute configuration of the amino acid by circular dichroism.
- Liang, Qing-Feng,Liu, Juan-Juan,Chen, Jian
-
experimental part
p. 3987 - 3991
(2011/08/09)
-
- A class of novel Schiff's bases: Synthesis, therapeutic action for chronic pain, anti-inflammation and 3D QSAR analysis
-
To discover analgesics for treating chronic pain 17 novel Schiff's bases, N,N′-(Z-allylidene-1,3-diyl)bisamino acid methyl esters were prepared from 1,1,3,3,-tetramethoxypropane and amino acid methyl esters. On tail-flick mouse model 20 μmol/kg of these Schiff's bases were orally administered, the analgesic action started 30 min after administration, reached the maximum 120 min after administration, and at 180 min this action was still observed. On a xylene-induced ear edema mouse model 20 μmol/kg of these Schiff's bases exhibited desirable anti-inflammation. Thus the present Schiff's bases are able to treat chronic pain from inflammation. The effect of the side chains of the amino acid residues of these Schiff's bases on the analgesic activity was explained with 3D QSAR.
- Zhou, Yinjian,Zhao, Ming,Wu, Yingting,Li, Chunyu,Wu, Jianhui,Zheng, Meiqing,Peng, Li,Peng, Shiqi
-
experimental part
p. 2165 - 2172
(2010/05/18)
-
- N-benzyl-protection of amino acid derivatives by reductive alkylation with α-picoline-borane
-
A convenient method for N-protection of amino acid derivatives with a benzyl group by reductive alkylation of amino acid derivatives with α-picoline-borane is described. Amino acid esters or amino alcohols were treated with aryl aldehydes in methanol/acetic acid in the presence of -picoline-borane to give N-benzyl-protected amino acid derivatives in good yields. Georg Thieme Verlag Stuttgart - New York.
- Kawase, Yasushi,Yamagishi, Takehiro,Kutsuma, Teruo,Kataoka, Tadashi,Ueda, Kimio,Iwakuma, Takeo,Nakata, Tadashi,Yokomatsu, Tsutomu
-
experimental part
p. 1673 - 1677
(2010/06/22)
-
- A simple synthesis of N β-Fmoc/Z-amino alkyl thiols and their use in the synthesis of N β-Fmoc/Z-amino alkyl sulfonic acids
-
A simple and efficient protocol for the synthesis of Nβ- Fmoc/Z-amino alkyl thiols is described. The approach uses sodium pyrosulfite-mediated hydrolysis of isothiouronium salts resulting from the reaction between N-protected aminoalkyl iodides and thiourea. N-Protected taurines were prepared through performic acid oxidation of the thiols and the products were further utilized for the synthesis of dipeptidosulfonamides. Georg Thieme Verlag Stuttgart - New York.
- Sureshbabu,Vishwanatha,Vasantha
-
experimental part
p. 1037 - 1042
(2010/07/06)
-
- Simplifying pyridoxal: Practical methods for amino acid dynamic kinetic resolution
-
Figure presented Metal complexes of picolinaldehyde are identified as low-cost and environmentally benign catalysts, providing high reaction rates and turnovers for the racemization of amino acids. These pyridoxal surrogates demonstrate activity toward a variety of amino acid esters. Applications to chemoenzymatic dynamic kinetic resolutions provide access to amino acids in high yields and with excellent enantioselectivities, demonstrating their compatibility with protease-mediated transformations.
- Felten, Albert E.,Zhu, Gangguo,Aron, Zachary D.
-
supporting information; experimental part
p. 1916 - 1919
(2010/07/06)
-
- 2,2-Bis(ethoxycarbonyl)vinyl (BECV) as a versatile amine protecting group for selective functional-group transformations
-
A 2,2-Bis(ethoxycarbonyl) vinyl- (BECV) group was used for the selective protection of amines at room temperature in the presence of potentially interfering functional groups such as OH, SH, COOH as well as other NH 2 groups. Several functional group transformations such as esterification, O-alkylation, O-acylation, N-alkylation, N-acylation, S-alkylation can selectively be carried out in the presence of the BECV group. The selective deprotection of the BECV group was achieved in a short time using ethylenediamine at room temperature while several other functional groups such as benzoate, aliphatic esters, amides and ethers remain intact. The BECV group shows orthogonal stability against the common protecting groups such as Fmoc, Cbz and Boc.
- Ilangovan, Andivelu,Kumar, Rajendran Ganesh
-
supporting information; experimental part
p. 2938 - 2943
(2010/07/02)
-
- New chiral building blocks of β-peptoid analogs
-
The synthesis of chiral functionalized β-amino esters via the hydride reductive amination of chiral allenes was explored. These compounds can be regarded as β-peptoids building blocks bearing a chiral side chain at the nitrogen and at the same time retaining the β-amino acid side chain. β-Enamino esters were obtained from the nucleophilic addition of α-amino esters (l-Ala, d-Ala, l-Phe, l-Leu, l-Trp and d-Trp methyl esters) to 2,3-allenoates bearing a chiral auxiliary, which determines the stereochemistry outcome of the subsequent reduction reaction. It was also demonstrated that in the reduction of β-enamino esters derived from l-Pro and d-Pro methyl esters the chirality of the new chiral center is controlled by the α-amino ester moiety.
- Cardoso, Ana Lúcia,Lopes, Susana M.M.,Matos Beja, Ana,Ramos Silva, Manuela,de los Santos, Jesús M.,Pinho e Melo, Teresa M.V.D.,Palacios, Francisco
-
body text
p. 9116 - 9124
(2010/01/16)
-
- Synthesis and molecular recognition of novel multiimidazole cyclophanes
-
(Chemical Equation Presented) Cyclophanes based on 2,2′-biimidazole and 2,2′-bibenzimidazole were synthesized as receptors. UV spectroscopic titration in chloroform at 25°C showed 1:1 complexes between the cyclophanes and the guests, and the binding constants (K) and Gibbs free energy changes (-ΔG0) were calculated according to the modified Benesi-Hildebrand equation.
- Xu, Xiao-Wei,Wang, Xin-Long,Wu, Ai-Ming,Zheng, Zhi-Ming,Yi, Mei-Gui,Xiao, Rong
-
experimental part
p. 1137 - 1141
(2010/03/01)
-
- Applications of the N-tert-butylsulfonyl (Bus) protecting group in amino acid and peptide chemistry
-
The utility of the tert-butylsulfonyl group (Bus) for the temporary protection of amino acids and peptides is reported. Compatibility and orthogonality in the presence of other N- and O-protecting groups were studied.
- Hanessian, Stephen,Wang, Xiaotian
-
experimental part
p. 2803 - 2808
(2010/03/03)
-
- Deprotectlon of N-Nosyl-α-amlno acids by using solid-supported mercaptoacetic acid
-
A simple and efficient synthesis of a solid-supported thiol has been developed. Mercaptoacetic acid was first protected by the dimethoxytrityl group and then anchored to Wang resin through an ester bond. Deprotection of the thiol function led to resin-supported mercaptoacetic acid, a useful supported thiol reagent that can be used in the polymer-assisted solution-phase removal of nosyl (Ns) groups from the amino function of a-amino acids in peptide synthesis.
- De Marco, Rosaria,Gioia, Maria Luisa Di,Leggio, Antonella,Liguori, Angelo,Viscomi, Maria Caterina
-
experimental part
p. 3795 - 3800
(2009/12/05)
-
- Anthranilimide-based glycogen phosphorylase inhibitors for the treatment of Type 2 diabetes: 2. Optimization of serine and threonine ether amino acid residues
-
Optimization of the amino acid residue of a series of anthranilimide-based glycogen phosphorylase inhibitors is described leading to the identification of serine and threonine ether analogs. t-Butylthreonine analog 20 displayed potent in vitro inhibition of GPa, low potential for P450 inhibition, and excellent pharmacokinetic properties.
- Sparks, Steven M.,Banker, Pierette,Bickett, David M.,Clancy, Daphne C.,Dickerson, Scott H.,Garrido, Dulce M.,Golden, Pamela L.,Peat, Andrew J.,Sheckler, Lauren R.,Tavares, Francis X.,Thomson, Stephen A.,Weiel, James E.
-
scheme or table
p. 981 - 985
(2009/08/15)
-
- Synthesis and structure of 1,4-dipiperazino benzenes: Chiral terphenyl-type peptide helix mimetics
-
(Chemical Equation Presented) The terphenyl structure has been proven to be an ideal scaffold mimicking side-chain functionalities of peptidic α-helices. The synthesis of 1,4-dipiperazino benzenes, using stepwise transition metal-catalyzed N-arylation of chiral piperazines to a central benzene core is reported. The structure determination by X-ray crystallography reveals a geometrical arrangement of the hydrophobic side chains resembling the orientation of key i, i + 3, and i + 7 positions in a peptidic α-helix or in terphenyl helix mimetics.
- Maity, Prantik,Koenig, Burkhard
-
supporting information; experimental part
p. 1473 - 1476
(2009/04/10)
-
- Highly enantioselective aza Morita-Baylis-Hillman reaction catalyzed by bifunctional β-isocupreidine derivatives
-
The aza-MBH reaction of imines 1 and β-naphthyl acrylate 2 in the presence of C-6′ modified β-isocupreidine derivative 1c (0.1 equiv) and β-naphthol 5 (0.1 equiv) afforded the corresponding (3S)-aza-MBH adducts 4 in high yield and excellent enantiomeric excess. These catalytic conditions allowed the aliphatic imines to be employed for the first time as electrophilic partners of the aza-MBH reaction. The coexistence of two H-bond donors with different acidic strengths was found to be crucial for the observed high enantioselectivity. Copyright
- Abermil, Nacim,Masson, Geraldine,Zhu, Jieping
-
supporting information; scheme or table
p. 12596 - 12597
(2009/04/10)
-
- DPP4 INHIBITOR AND PHARMACEUTICAL APPLICATION THEREOF
-
The present invention provides a Dpp4 inhibitor which comprises a leucine derivative of the following formula (1) or a methionine derivative of the following formula (2): wherein each R1 and R3 represents a hydrogen atom (H) and an L-amino acid residue; R2 represents a hydroxyl group (OH), alkoxy group having 1 to 6 carbon atoms, amino group (NH2), alkylamino group having 1 to 6 carbon atoms, glycine residue, β-alanine residue, L-amino acid (except for proline, alanine and phenylalanine) residue or L-amino-acid amide (except for proline amide, alanine amide and phenylalanine amide) residue; and R4 represents a hydroxyl group (OH), alkoxy group having 1 to 6 carbon atoms, amino group (NH2), alkylamino group having 1 to 6 carbon atoms, glycine residue, β-alanine residue, L-amino acid (except for proline and alanine) residue or L-amino-acid amide (except for proline amide and alanine amide) residue. These derivatives also act as autophagy regulators.
- -
-
Page/Page column 8
(2008/06/13)
-
- Mechanism study on the oligomerization of amino acids into peptides by phosphorus trichloride
-
As treated by phosphorus trichloride, amino acids could oligomerize into polypeptides. Based on the results obtained by 31P-NMR and ESI-MS/MS, a possible reaction mechanism was proposed. The mechanism might undergo a penta-coordinated phosphorus intermediat. The activated amino acid was a five-membered cyclic penta-coordinated phosphorus intermediate. The nucleophilic attack of the amino group from an amino acid or peptide on the carbonyl group of intermediate led to the formation of peptide and released one equivalent dichloride phosphoric acid. The repetition of the reaction sequence generated a series of oligopeptides. Copyright Taylor & Francis Group, LLC.
- Zhao, Wenjie,Zhao, Dongxin,Lu, Kui
-
scheme or table
p. 691 - 698
(2009/05/07)
-
- Design and synthesis of a novel class of furan-based molecules as potential 20S proteasome inhibitors
-
A novel class of furan-based compounds as potential 20S proteasome inhibitors have been designed and synthesized, among which nine compounds are peptide derivatives and six molecules are statine peptidomimetics. The C-terminal furanyl moiety was introduced to target molecules as furan-based amino acids. All the compounds were obtained steadily with moderate to high yield. Compound 12 was a selective moderate potent proteasome peptidomimetic inhibitor. It inhibited HepG2 and HL-60 proliferation effectively.
- Fu, Yiqiu,Xu, Bo,Zou, Xiaomin,Ma, Chao,Yang, Xiaoming,Mou, Ke,Fu, Gang,Lue, Yang,Xu, Ping
-
p. 1102 - 1106
(2007/10/03)
-
- LCST-type phase changes of a mixture of water and ionic liquids derived from amino acids
-
(Figure Presented) Out of phase: Ionic liquids (ILs) derived from amino acids exhibit phase separation with a lower critical solution temperature after mixing with water (see picture; upper phase water; lower phase IL). The phase-separation temperature of these mixtures depends on the ion structure and water content, and is lowered by an increase in the hydrophobicity of the ionic liquid.
- Fukumoto, Kenta,Ohno, Hiroyuki
-
p. 1852 - 1855
(2008/02/12)
-
- Azabicyclo[3.1.0]hexane-1-ols as frameworks for the asymmetric synthesis of biologically active compounds
-
Azabicyclo[3.1.0]hexane-1-ols, easily obtained by Ti(IV)-mediated cyclopropanation of amino acid derivatives, constitute versatile, and unprecedented intermediates for the asymmetric synthesis of pharmacologically active products. Indeed, through selective rearrangement, these compounds undergo unusual ring cleavage to lead to pyrrolidinones. Fe(III)-promoted ring opening followed by basic dehydrohalogenation furnishes optically active dihydropyridinones, while Ce(IV)-promoted ring opening provides chiral tricyclopiperidinones via a radical process.
- Jida, Mouhamad,Guillot, Régis,Ollivier, Jean
-
p. 8765 - 8767
(2008/03/18)
-
- Enantioselective benzoylation of α-amino esters using (S)-1-benzoyl-2-(α-acetoxyethyl)benzimidazole, a chiral benzimidazolide
-
(Chemical Equation Presented) A new chiral benzimidazolide is developed as a nonenzymatic acylating agent for enantioselective benzoylation of racemic α-amino esters. The process is highly efficient, which exhibits uniformly high enantioselectivity for α-amino esters with or without aryl substituents under mild reaction conditions. The chiral benzimidazolide is inexpensive and is easily accessible.
- Karnik, Anil V.,Kamath, Suchitra S.
-
p. 7435 - 7438
(2008/02/11)
-
- Methods and compositions for treating amyloid-related diseases
-
Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.
- -
-
Page/Page column 135-136
(2010/11/24)
-