- A highly substituted pyrazinophane generated from a quinoidal system: Via a cascade reaction
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The generation of a highly-substituted [2.2](2,5)pyrazinophane via a cascade reaction is presented. The pyrazinophane product is formed via the dimerization of a member of the para-azaquinodimethane (p-AQM) family of conjugated quinoidal compounds - reactivity that sheds light on the nature of stability in p-AQMs. Additionally, the electronic and structural nature of this highly-strained ring system are characterized.
- Anderson, Christopher L.,Garzón-Ruiz, Andrés,Liang, Jiatao,Liu, Yi,Navarro, Amparo,Nenon, David P.,Teat, Simon J.
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- Synthesis and unusual ring transformation of 1-acyl-3- (ferrocenylmethylidene)-piperazine-2,5-diones
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The reaction of 1,4-diacyl-piperazine-2,5-diones with ferrocenecarbaldehyde in the presence of tBuOK in tBuOH-DMF at room temperature afforded 1-acyl-3-(ferrocenylmethylidene)-piperazine-2,5-diones in 69-79% yields. The attempted N(4)-acylation of these compounds with carboxylic acids (2 equiv.) in the presence of N,N′-diisopropylcarbodiimide (2 equiv.) and 4-(dimethylamino)pyridine (3 equiv.) in dichloromethane at room temperature showed that the expected 1,4-diacylated products are initially formed, but undergo further transformations leading to compounds featuring conjugated ferrocenylmethylidene, azlactone (oxazolone) and oxazole units. As shown on the basis of one example, the azlactone ring in these compounds is opened in a room-temperature reaction with hydrazine, thus yielding the corresponding acyl hydrazide. The crystal structure of the starting material and the product of this reaction were confirmed by X-ray diffraction.
- Wieczorek, Anna,Plazuk, Damian,Zakrzewski, Janusz,Makal, Anna,Wo?niak, Krzysztof
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- Phenotype-Guided Natural Products Discovery Using Cytological Profiling
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Phenotype-guided natural products discovery is emerging as a useful new discovery tool that addresses challenges in early, unbiased natural product biological annotation. These high-content approaches yield screening results that report directly on the im
- Ochoa, Jessica L.,Bray, Walter M.,Lokey, R. Scott,Linington, Roger G.
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- Radical addition of simple piperazine-2,5-diones
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The polar character of a simple piperazine-2,5-dione was investigated under intermolecular radical addition conditions. The results indicate that captodative radical of this kind neither show extreme nucleophilic nor electrophilic tendencies.
- Chai,Page
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Read Online
- Chiral 1,2,3-Triazolium Salt Catalyzed Asymmetric Mono- and Dialkylation of 2,5-Diketopiperazines with the Construction of Tetrasubstituted Carbon Centers
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Novel asymmetric mono- and dialkylation reactions of α-substituted 2,5-diketopiperazines catalyzed by new chiral spirocyclic-amide-derived triazolium organocatalysts have been developed, resulting in a range of enantioenriched 2,5-diketopiperazine derivatives containing one or two tetrasubstituted carbon stereocenters. The reactions feature high yields (up to 98%), and excellent cis-diastereo- and enantioselectivities (up to >20:1 dr, >99 % ee), and they provide a new asymmetric synthetic approach to important functionalized 2,5-diketopiperazine skeletons. Furthermore, a possible reaction mechanism was proposed based on both control experiments and extensive DFT calculations.
- Yang, Ju-Song,Lu, Ka,Li, Chen-Xiao,Zhao, Zu-Hang,Zhang, Xiao-Ming,Zhang, Fu-Min,Tu, Yong-Qiang
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supporting information
(2022/01/22)
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- Histamine H3 receptor antagonists with peptidomimetic (keto)piperazine structures to inhibit Aβ oligomerisation
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Alzheime?s disease (AD) is the most prominent neurodegenerative disorder with high medical need. Protein-protein-interactions (PPI) interactions have a critical role in AD where β-amyloid structures (Aβ) build toxic oligomers. Design of disease modifying multi target directed ligand (MTDL) has been performed, which disable PPI on the one hand and on the other hand, act as procognitive antagonists at the histamine H3 receptor (H3R). The synthetized compounds are structurally based on peptidomimetic amino acid-like structures mainly as keto, diketo-, or acyl variations of a piperazine moiety connected to an H3R pharmacophore. Most of them showed low nanomolar affinities at H3R and some with promising affinity to Aβ-monomers. The structure–activity relationships (SAR) described offer new possibilities for MTDL with an optimized profile combining symptomatic and potential causal therapeutic approaches in AD.
- Falkenstein, Markus,Reiner-Link, David,Zivkovic, Aleksandra,Gering, Ian,Willbold, Dieter,Stark, Holger
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- One pot synthesis of N-monoalkylated plinabulin derivatives via multicomponent protocol and their application as anticancer agents
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A chemical library of seventeen N-monoalkylated plinabulin derivatives was designed and synthesized in one pot with high atom economy, good yield and operational simplicity in site selective manner with Z-configuration at 3,6-positions (3Z,6Z) which have
- Ganesher, Asha,Chaturvedi, Priyank,Karkara, Bidhu Bhusan,Chatterjee, Indranil,Datta, Dipak,Panda, Gautam
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- Enantioselective Synthesis of Chiral Substituted 2,4-Diketoimidazolidines and 2,5-Diketopiperazines via Asymmetric Hydrogenation
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An enantioselective hydrogenation of 5-alkylidene-2,4-diketoimidazolidines (hydantoins) and 3-alkylidene-2,5-ketopiperazines catalyzed by the Rh/f-spiroPhos complex under mild conditions has been developed, which provides an efficient approach to the highly enantioselective synthesis of chiral hydantoins and 2,5-ketopiperazine derivatives with high enantioselectivities up to 99.9% ee.
- Xiao, Guiying,Xu, Shuang,Xie, Chaochao,Zi, Guofu,Ye, Weiping,Zhou, Zhangtao,Hou, Guohua,Zhang, Zhanbin
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supporting information
p. 5734 - 5738
(2021/08/01)
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- The synthesis and biological activity of the 3-ferrocenylpropenamides derived from 5(4H)-oxazolones
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We described a synthesis of new 3-ferrocenylpropenamides prepared by oxazolone-ring opening reaction with various primary and secondary amines. The antiproliferative activities of the obtained compounds were screened on human tumor cell lines (HCT116, SW6
- Wieczorek-B?au?, Anna,B?au?, Andrzej,Rychlik, B?a?ej,Pla?uk, Damian
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- DL-neopentyl glycine intermediate and preparation method thereof and preparation method of derivative based on intermediate
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The invention relates to the field of amino acid preparation, in particular to a DL-neopentyl glycine intermediate and a preparation method thereof and a preparation method of a derivative based on the intermediate. The preparation method of the DL-neopentyl glycine intermediate comprises an acetylation reaction, a condensation reaction, a hydrolysis reaction, an oximation reaction and a reductionreaction, and then a corresponding derivative is obtained through the acetylation reaction and resolution. According to the preparation method, the reaction time is shortened, the reaction is more thorough and the DL-neopentyl glycine can be obtained; two methods for preparing the derivative D-neopentyl glycine and the derivative L-neopentyl glycine are obtained at the same time, the prepared product is high in purity, secondary refining is not needed, the production cost is reduced, and industrial large-scale production is facilitated.
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Paragraph 0033; 0035; 0046; 0048; 0059; 0061
(2020/05/08)
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- Synthetic studies towards the penicisulfuranols: Synthesis of an advanced spirocyclic diketopiperazine intermediate
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The 2,5-diketopiperazine (DKP) moiety is a core feature of many natural products and medicinally relevant scaffolds. As part of our efforts directed towards a total synthesis of penicisulfuranol B, we have developed and report herein: (1) the preparation of an N-hydroxy diketopiperazine intermediate accessible via a molybdenum-mediated oxidation of a parent diketopiperazine, and (2) further synthetic studies leading to a novel spirocyclic dihydrobenzofuran-containing diketopiperazine.
- Gayler, Kevin M.,Lambert, Kyle M.,Wood, John L.
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supporting information
p. 3154 - 3159
(2019/01/29)
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- Plinabulin compound polycrystalline type and preparation method thereof
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The invention provides a plinabulin compound polycrystalline type and a preparation method thereof, and particularly relates to a polycrystalline type of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) methylene)piperazidine-2,5-diketone and a preparation method thereof. Three kinds of crystalline types beta, gamma and delta are developed on the basis of the crystalline type alpha of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) methylene)piperazidine-2,5-diketone, wherein the three kinds of crystalline types beta, gamma and delta can be prepared into monocrystallines; the three kinds of crystalline types have the advantages of clear conformation, high purity and high method repeatability; the important significance is realized on implementation of plinabulin biological effectiveness study and dosage form variety development.
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Paragraph 0047; 0048
(2017/08/31)
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- Preparation and purification method of high-purity Plinabulin compound
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The invention provides a preparation and purification method of high-purity Plinabulin compound, which aims at mainly removing a trans-isomer. The preparation and purification method has the advantages that (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)methylene)piperazine-2,5-diketone monohydrate and (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)deuterated methylene)piperazine-2,5-diketone monohydrate are prepared; the purity of the prepared product is higher than 99.5%, and the content of the trans-isomer is smaller than 0.1%. The invention also relates to the preparation and purification of important intermediates, such as 5-(tert-butyl)-1H-imidazole-4-ethyl formate and 1,4-diacetylpiperazine-2,5-diketone. The preparation and purification method has the advantages that the production cost is reduced, the pos-treatment difficulty is decreased, and the technology more meets the requirements of industrialized production.
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Paragraph 0027; 0029; 0033
(2017/08/31)
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- The compound for anti-skin aging and skin wrinkle improving
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Provided is a composition applicable to alleviate skin wrinkles by obtaining and using particular components derived from salted seafood through extraction. Preferably, the compound can be used as a cosmetic composition comprising at least one among composition 1: L-Pro-L-Tyr, composition 2: L-Pro-L-Phe, and composition 3: L-Pro-L-Val. By using natural materials derived from salted seafood, a novel material free of side effects can be easily obtained, and an effect of reducing costs of production can be obtained accordingly. Also, materials which can be applied on the exterior of the skin can be obtained. Thus, suggested is a novel way to alleviate skin wrinkles by using naturally derived materials.COPYRIGHT KIPO 2016
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Paragraph 0061
(2017/06/10)
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- Enantiomerically pure 3-aryl- and 3-hetaryl-2-hydroxypropanoic acids by chemoenzymatic reduction of 2-oxo acids
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Phenyllactic acids are found in numerous natural products as well as in active substances used in medicine or plant protection. Enantiomerically pure phenyllactic acids are available by transition-metal-catalyzed hydrogenations or chemoenzymatic reductions of the corresponding 3-aryl-2-oxopropanoic acids. We show here that d-lactate dehydrogenase from Staphylococcus epidermidis reduces a broad spectrum of 2-oxo acids, which are difficult substrates for transition-metal-catalyzed reactions, with excellent enantioselectivities in a simple experimental setup.
- Sivanathan, Sivatharushan,K?rber, Florian,Tent, Jannis Aron,Werner, Svenja,Scherkenbeck, Jürgen
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p. 2554 - 2561
(2015/03/18)
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- One-pot synthesis of polysubstituted 3-amino-2-oxo-2,7-dihydro-1 H -azepines
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A facile and efficient synthesis of novel seven-membered heterocyclic derivatives containing 3-aminoazepan-2-one backbone is described using 1,4-protected piperazine-2,5-diones and alkynes as starting materials. The reaction may undergo Michael? addition,
- Liao, Shengrong,Qin, Chun,Yao, Peifen,Li, Jinsheng,Zhou, Xuefeng,Wang, Junfeng,Huang, Zhishu,Liu, Yonghong
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p. 621 - 628
(2014/03/21)
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- Design and synthesis of novel soluble 2,5-diketopiperazine derivatives as potential anticancer agents
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Non-protected 2,5-diketopiperazine derivatives have poor solubility thus with negative impact on their bioavailability. In the present study, twenty-one novel soluble mono-protected, and three non-protected 2,5-diketopiperazine derivatives were designed and synthesized. Their anticancer activity to ten cell lines were evaluated by using CCK8 assay, and the results showed that about half of the mono-protected derivatives had broad-spectrum anticancer activity. Among allyl-protected derivatives, compound 4m had strong activity to all the cell lines (IC50 = 0.5-4.5 μM), especially to the cancer cell lines U937 (IC50 = 0.5 μM) and K562 (IC50 = 0.9 μM). Compound 4m could become a lead compound for further development for anticancer agents.
- Liao, Shengrong,Qin, Xiaochu,Li, Ding,Tu, Zhengchao,Li, Jinsheng,Zhou, Xuefeng,Wang, Junfeng,Yang, Bin,Lin, Xiuping,Liu, Juan,Yang, Xianwen,Liu, Yonghong
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p. 236 - 244
(2014/07/08)
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- Novel approach to the synthesis of aliphatic and aromatic α-keto acids
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A new practical and efficient synthesis of α-keto acids was accomplished starting from the synthon 1,4-diacetylpiperazine-2,5-dione. The synthesis encompasses both aromatic and aliphatic substrates proving to be versatile and innovative with excellent carbon economy and recycling of the glycine by-product.
- Balducci, Daniele,Conway, Philip A.,Sapuppo, Giulia,Müller-Bunz, Helge,Paradisi, Francesca
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experimental part
p. 7374 - 7379
(2012/09/10)
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- Transannular rearrangement of activated 2,5-diketopiperazines: A key route to original scaffolds
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An efficient and original stereocontrolled transannular rearrangement starting from activated 2,5-diketopiperazines has been developed, an opportunity for the medicinal chemistry field, which requests access to novel biological scaffolds. This powerful ri
- Farran, Daniel,Parrot, Isabelle,Toupet, Loic,Martinez, Jean,Dewynter, Georges
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experimental part
p. 3989 - 3996
(2009/06/28)
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- ANALOGS OF DEHYDROPHENYLAHISTINS AND THEIR THEAPEUTIC USE
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Compounds represented by the following structure (II) are disclosed: as are methods for making such compounds. Compositions and methods for treating various disease conditions including cancer and non-cancer diseases associated with vascular proliferation are also disclosed.
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Page/Page column 18; 31
(2008/12/08)
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- Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof
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Compounds represented by the following structure (I) are disclosed: as are methods for making such compounds, wherein said methods comprise reacting a diacyldiketopiperazine with a first aldehyde to produce an intermediate compound; and reacting the intermediate compound with a second aldehyde to produce the class of compounds with the generic structure, where the first aldehyde and the second aldehydes are selected from the group consisting of an oxazolecarboxaldeyhyde, imidazolecarboxaldehyde, a benzaldehyde, imidazolecarboxaldehyde derivatives, and benzaldehyde derivatives, thereby forming the above compound wherein R1, R1′, R1″, R2, R3, R4, R5, and R6, X1 and X2, Y, Z, Z1, Z2, Z3, and Z4 may each be separately defined in a manner consistent with the accompanying description. Compositions and methods for treating vascular proliferation are also disclosed.
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- Five- and six-membered ring opening of pyroglutamic diketopiperazine
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A variety of ring-opening reactions of pyroglutamic diketopiperazine at both the five-membered and six-membered rings is described. Mild, basic conditions facilitate nucleophilic attack by amines at the diketopiperazine carbonyls giving pyroglutamides in excellent yield. Reaction with nucleophiles under acidic conditions give bis-glutamate derivatives of 2,5-diketopiperazine (DKP). These reactions provide simple, two-step sequences to pyroglutamides and symmetrical diketopiperazines from commercial pyroglutamic acid with control of product dictated by reaction conditions, catalyst, and nucleophile.
- Parrish, Dennis A.,Mathias, Lon J.
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p. 1820 - 1826
(2007/10/03)
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- Synthesis and in vitro evaluation of a series of diketopiperazine inhibitors of plasminogen activator inhibitor-1
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We have synthesized and evaluated a series of diketopiperazine-based inhibitors of PAI-1. These studies resulted in the identification of 34 which inhibited PAI-1 in vitro with an IC50 = 0.2 μM. The synthesis and SAR of these compounds are desc
- Folkes, Adrian,Roe, Michael B.,Sohal, Sukhjit,Golec, Julian,Faint, Richard,Brooks, Teresa,Charlton, Peter
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p. 2589 - 2592
(2007/10/03)
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- Liquid-crystalline properties of unsaturated piperazine-2,5-dione derivatives
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The synthesis, characterization, and mesomorphic properties of a new type of liquid-crystalline compounds, (3Z,6Z)-3,6-bis(3,4- dialkoxybenzylidene)piperazine-2,5-diones are reported. These compounds were derived from unsaturated piperazine-2,5-dione as t
- Li, Wen-Ren,Kao, Kwo-Cheng,Yo, Ying-Chih,Lai, Chung K.
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p. 1400 - 1407
(2007/10/03)
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- Inhibition of plasminogen activator inhibitor-1 activity by two diketopiperazines, XR330 and XR334 produced by Streptomyces sp.
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Two diketopiperazines, XR334 (1) and the novel compound XR330 (2), were isolated from the lyophilised biomass of an unidentified Streptomyces sp. Their structures were elucidated on the basis of spectroscopic studies and confirmed by chemical synthesis. B
- Bryans, Justin,Charlton, Peter,Chicarelli-Robinson, Ines,Collins, Mark,Faint, Richard,Latham, Chris,Shaw, Ian,Trew, Sally
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p. 1014 - 1021
(2007/10/03)
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- Alternative Synthesis of 6-(3-Methoxybenzyl)pyrazin-2(1H)-one. Synthesis of Indenopyrazin-2-ones. Crystal Structures of 5-Acetoxy-1-benzyl-4-tert-butoxycarbonyl-6-(3-methoxybenzylidene)piperazin-2-one,...
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1-Acetyl-3-(3-methoxybenzylidene)piperazine-2,5-dione 7a was converted via a 7-step sequence into 6-(3-methoxybenzyl)pyrazin-2(1H)-one 2a.Treatment of 1-benzyl-4-tert-butoxycarbonyl-5-hydroxy-6-(3-methoxybenzylidene)piperazin-2-one 8a with acids results i
- Peters, David A.,Beddoes, Roy L.,Joule, John A.
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p. 1217 - 1224
(2007/10/02)
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- Saframycin synthetic studies
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A conceptually simple and direct synthetic route to racemic saframycyn B, a bis-isoquinoline quinone antitumor antibiotic, was studied relying on transformations of a key C-2 symmetric intermediate.
- Shawe, Thomas T.,Liebeskind, Lanny S.
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p. 5643 - 5666
(2007/10/02)
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- Pyrazine Chemistry. Part 14. On the Preparation and Oxygenation of Pyrazines and Some Reactions of the Product Peroxides
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Some new methods for preparing substituted pyrazines are reported. 2,6-Dimethoxy substituted pyrazines undergo facile addition of singlet oxygen to form endoperoxides, some of which are remarkably stable.The behaviour of these compounds has been explored.In particular, deoxygenation is effected with triphenylphosphine to induce skeletal rearrangements, the pyrazines undergoing ring contraction to substituted imidazoles.The rearrangement occurs via intermediate oxadiazepines which can be intercepted by intramolecular trapping with a pendant hydroxy group, leading to a novel method for entry into the 3,6,1-oxadiazepine system.Reductive cleavage of the peroxide bond leads to unstable dihydroxydihydropyrazines.
- Dawson, Ian M.,Pappin, Amanda J.,Peck, Colin J.,Sammes, Peter G.
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p. 453 - 461
(2007/10/02)
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