- 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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- Sulfated and Oxygenated Imidazoline Derivatives: Synthesis, Antioxidant Activity and Light-Mediated Antibacterial Activity
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Imidazoline derivatives with different exocyclic substituents were simply prepared from common starting materials. The procedures were carried out in an eco-friendly manner. The antioxidant activity of these derivatives was explored by different experimental assays, such as ABTS.+ and DPPH. scavenging assay, as well as reducing power assay. The structural differences are discussed in terms of the results. Sulfur analogs showed higher antioxidant activity than their oxygenated counterparts. The same tendency was observed in microbiological studies, in which the same imidazoline compounds were assayed for light-mediated activity against of Staphylococcus aureus and Escherichia coli strains. A light-enhanced activity was observed for almost all the sulfated imidazolines after exposure to UV-A (400-320 nm) light.
- Alves Borges Leal, Antonio L.,Barreto, Humberto M.,Faillace, Martín S.,Muratori da Costa, Luciana,Peláez, Walter J.,Silva, Ana P.
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- Discovery of novel UV-filters with favorable safety profiles in the 5-arylideneimidazolidine-2,4-dione derivatives group
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Effective protection from the harmful effects of UV radiation may be achieved by using sunscreens containing organic or inorganic UV filters. The number of currently available UV filters is limited and some of the allowed molecules possess limitations such as systemic absorption, endocrine disruption properties, contact and photocontact allergy induction, and low photostability. In the search for new organic UV filters we designed and synthesized a series consisting of 5-benzylidene and 5-(3-phenylprop-2-en-1-ylidene)imidazolidine-2,4-dione (hydantoin) derivatives. The photoprotective activity of the tested compounds was confirmed in methanol solutions and macrogol formulations. The most promising compounds possessed similar UV protection parameter values as selected commercially available UV filters. The compound diethyl 2,20-((Z)-4-((E)-3-(4-methoxyphenyl)allylidene)-2,5-dioxoimidazolidine-1,3-diyl)diacetate (4g) was characterized as an especially efficient UVA photoprotective agent with a UVA PF of 6.83 ± 0.05 and favorable photostability. Diethyl 2,20-((Z)-4-(4-methoxybenzylidene)-2,5-dioxo-imidazolidine-1,3-diyl)diacetate (3b) was the most promising UVB-filter, with a SPFin vitro of 3.07 ± 0.04 and very good solubility and photostability. The main photodegradation products were geometric isomers of the parent compounds. These compounds were also shown to be non-cytotoxic at concentrations up to 50 μM when tested on three types of human skin cells and possess no estrogenic activity, according to the results of a MCF-7 breast cancer model.
- Popió?, Justyna,Gunia-Krzyzak, Agnieszka,Piska, Kamil,Zelaszczyk, Dorota,Koczurkiewicz, Paulina,S?oczynska, Karolina,Wójcik-Pszczo?a, Katarzyna,Krupa, Anna,Kryczyk-Poprawa, Agata,Zes?awska, Ewa,Nitek, Wojciech,Zmudzki, Pawe?,Marona, Henryk,Pekala, Elzbieta
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- Chemoenzymatic synthesis of L-3,4-dimethoxyphenyl-alanine and its analogues using aspartate aminotransferase as a key catalyst
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In this study, a chemoenzymatic synthesis method for the production of L-3,4-dimethoxyphenyl-alanine and its analogues from phenylpyruvate derivatives was developed. The aspartate aminotransferase from Escherichia coli was engineered by error prone PCR and the improved variants were identified. When 3, 4-dimethoxy phenylpyruvate was added by fed-batch on a preparative scale, L-3,4-dimethoxyphenyl-alanine was formed in 95.4% conversion and > 99% ee with the best aspartate aminotransferase variant as the catalyst. This study provided an efficient method for the production of methoxy substituted phenylalanines using the engineered aspartate aminotransferase.
- Yu, Jinhai,Li, Jing,Cao, Shuangyan,Wu, Ting,Zeng, Shuiyun,Zhang, Hongjuan,Liu, Junzhong,Jiao, Qingcai
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-
- Evaluation of α-hydroxycinnamic acids as pyruvate carboxylase inhibitors
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Through a structure-based drug design project (SBDD), potent small molecule inhibitors of pyruvate carboxylase (PC) have been discovered. A series of α-keto acids (7) and α-hydroxycinnamic acids (8) were prepared and evaluated for inhibition of PC in two assays. The two most potent inhibitors were 3,3′-(1,4-phenylene)bis[2-hydroxy-2-propenoic acid] (8u) and 2-hydroxy-3-(quinoline-2-yl)propenoic acid (8v) with IC50 values of 3.0 ± 1.0 μM and 4.3 ± 1.5 μM respectively. Compound 8v is a competitive inhibitor with respect to pyruvate (Ki = 0.74 μM) and a mixed-type inhibitor with respect to ATP, indicating that it targets the unique carboxyltransferase (CT) domain of PC. Furthermore, compound 8v does not significantly inhibit human carbonic anhydrase II, matrix metalloproteinase-2, malate dehydrogenase or lactate dehydrogenase.
- Burkett, Daniel J.,Wyatt, Brittney N.,Mews, Mallory,Bautista, Anson,Engel, Ryan,Dockendorff, Chris,Donaldson, William A.,St. Maurice, Martin
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p. 4041 - 4047
(2019/08/26)
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- Synthesis of chiral hydantoin derivatives by homogeneous Pd-catalyzed asymmetric hydrogenation
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5-Aryl substituted chiral hydantoin derivatives were synthesized via asymmetric hydrogenation of prochiral exocyclic alkenes using a Pd/BINAP catalyst. Moderate to good enantioselectivity were obtained (21–90% ee). A chiral Br?nsted acid additive was foun
- Ma, Bao-De,Du, Sheng-Hua,Wang, Yu,Ou, Xiao-Ming,Huang, Ming-Zhi,Wang, Li-Xin,Wang, Xiao-Guang
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-
- Identification of a New Zinc Binding Chemotype by Fragment Screening
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The discovery of a new zinc binding chemotype from screening a nonbiased fragment library is reported. Using the orthogonal fragment screening methods of native state mass spectrometry and surface plasmon resonance a 3-unsubstituted 2,4-oxazolidinedione fragment was found to have low micromolar binding affinity to the zinc metalloenzyme carbonic anhydrase II (CA II). This affinity approached that of fragment sized primary benzenesulfonamides, the classical zinc binding group found in most CA II inhibitors. Protein X-ray crystallography established that 3-unsubstituted 2,4-oxazolidinediones bound to CA II via an interaction of the acidic ring nitrogen with the CA II active site zinc, as well as two hydrogen bonds between the oxazolidinedione ring oxygen and the CA II protein backbone. Furthermore, 3-unsubstituted 2,4-oxazolidinediones appear to be a viable starting point for the development of an alternative class of CA inhibitor, wherein the medicinal chemistry pedigree of primary sulfonamides has dominated for several decades.
- Chrysanthopoulos, Panagiotis K.,Mujumdar, Prashant,Woods, Lucy A.,Dolezal, Olan,Ren, Bin,Peat, Thomas S.,Poulsen, Sally-Ann
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p. 7333 - 7349
(2017/09/22)
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- Bioisosteric modification of known fucosidase inhibitors to discover a novel inhibitor of α-l-fucosidase
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Bioisosteric modification of known fucosidase inhibitors A and B, resulted in three new types of molecules, 4b, 5c and 6a (belonging to furopyridinedione, thiohydantoin and hydantoin chemotypes) that could potentially bind to α-l-fucosidase (bovine kidney
- Bathula, Chandramohan,Ghosh, Shreemoyee,Hati, Santanu,Tripathy, Sayantan,Singh, Shailja,Chakrabarti, Saikat,Sen, Subhabrata
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p. 3563 - 3572
(2017/01/25)
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- Hydantoin-based molecular photoswitches
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A new family of molecular photoswitches based on arylidenehydantoins is described together with their synthesis and photochemical and photophysical studies. A series of hydantoin derivatives have been prepared as single isomers using simple and versatile chemistry in good yields. Our studies show that the photostationary states of these compounds can be easily controlled by means of external factors, such as the light source or filters. Moreover, the detailed investigations proved that these switches are efficient (i.e., they make efficient use of the light energy, are high fatigue resistant, and are very photostable). In some cases, the switches can be completely turned on/off, a desirable feature for specific applications. A series of theoretical calculations have also been carried out to understand the photoisomerization mechanism at the molecular level.
- Martínez-López, David,Yu, Meng-Long,García-Iriepa, Cristina,Campos, Pedro J.,Frutos, Luis Manuel,Golen, James A.,Rasapalli, Sivappa,Sampedro, Diego
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p. 3929 - 3939
(2015/05/05)
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- SHIKIMATE PATHWAY INHIBITORS AND THE USE THEREOF
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The present invention relates to methods of inhibiting shikimate pathway, comprising administering to a subject a pharmaceutically acceptable composition comprising a compound having a formula: or pharmaceutically acceptable salts thereof. The present invention also provides a synergistic antibacterial composition containing compound
- -
-
Paragraph 0041;0042
(2015/05/26)
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- Systematic Evaluation of the Metabolism and Toxicity of Thiazolidinone and Imidazolidinone Heterocycles
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The thiazolidine and imidazolidine heterocyclic scaffolds, i.e., the rhodanines, 2,4-thiazolidinediones, 2-thiohydantoins, and hydantoins have been the subject of debate on their suitability as starting points in drug discovery. This attention arose from the wide variety of biological activities exhibited by these scaffolds and their frequent occurrence as hits in screening campaigns. Studies have been conducted to evaluate their value in drug discovery in terms of their biological activity, chemical reactivity, aggregation-based promiscuity, and electronic properties. However, the metabolic profiles and toxicities have not been systematically assessed. In this study, a series of five-membered multiheterocyclic (FMMH) compounds were selected for a systematic evaluation of their metabolic profiles and toxicities on TAMH cells, a metabolically competent rodent liver cell line and HepG2 cells, a model of human hepatocytes. Our studies showed that generally the rhodanines are the most toxic, followed by the thiazolidinediones, thiohydantoins, and hydantoins. However, not all compounds within the family of heterocycles were toxic. In terms of metabolic stability, 5-substituted rhodanines and 5-benzylidene thiohydantoins were found to have short half-lives in the presence of human liver microsomes (t1/2 30 min) suggesting that the presence of the endocyclic sulfur and thiocarbonyl group or a combination of C5 benzylidene substituent and thiocarbonyl group in these heterocycles could be recognition motifs for P450 metabolism. However, the stability of these compounds could be improved by installing hydrophilic functional groups. Therefore, the toxicities and metabolic profiles of FMMH derivatives will ultimately depend on the overall chemical entity, and a blanket statement on the effect of the FMMH scaffold on toxicity or metabolic stability cannot and should not be made.
- Tang, Shi Qing,Lee, Yong Yang Irvin,Packiaraj, David Sheela,Ho, Han Kiat,Chai, Christina Li Lin
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p. 2019 - 2033
(2015/11/02)
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- Evaluation of michael-type acceptor reactivity of 5-benzylidenebarbiturates, 5-benzylidenerhodanines, and related heterocycles using NMR
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Despite existing experimental and computational tools to assess the risk, the non-specific chemical modification of protein thiol groups remains a significant source of false-positive hits, particularly in academic drug discovery. Herein, we describe the
- Arsovska, Emilija,Trontelj, Jurij,Zidar, Nace,Tomai, Tihomir,Mai, Lucija Peterlin,Kikelj, Danijel,Plavec, Janez,Zega, Anamarija
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p. 637 - 644
(2014/12/11)
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- (S)-5-Benzyl- and 5-benzylidene-imidazo-4-one derivatives synthesized and studied for an understanding of their thermal reactivity
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Flash vacuum as well as static pyrolysis were used to gain insight into the mechanisms of decomposition of the title compounds. They were synthesized by the use of microwave techniques that allowed better yields than the established methods. Since the benzyl compounds always open a radical channel in the thermal processes, consequently lowering the yields of other important intramolecular processes, we also started the pyrolysis with benzylidene derivatives. Detection and quantification of products accompanied by kinetic analyses were carried out for both types of compounds. The activation energies as well as the entropy contributions have been determined. Moreover, DFT calculations provided support for and corroborating of the proposed thermal pathways.
- Pepino,Pelez,Faillace,Ceballos,Moyano,Argüello
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p. 60092 - 60101
(2015/02/19)
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- Search for new tools to combat Gram-negative resistant bacteria among amine derivatives of 5-arylidenehydantoin
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A series of amine-alkyl derivatives of 5-arylidenehydantoin 3-21 was evaluated for their ability to improve antibiotic effectiveness in two strains of Gram-negative Enterobacter aerogenes: the reference strain (ATCC-13048) and the chloramphenicol-resistan
- Handzlik, Jadwiga,Szymańska, Ewa,Alibert, Sandrine,Chevalier, Jacqueline,Otr?bska, Ewa,P?kala, Elzbieta,Pagès, Jean-Marie,Kie?-Kononowicz, Katarzyna
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p. 135 - 145
(2013/02/23)
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- Expedient base-mediated desulfitative dimethylamination, oxidation, or etherification of 2-(Methylsulfanyl)-3,5-dihydro-4 H -imidazol-4-one scaffolds
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The dimethylamino functionality is generally introduced onto the 3,5-dihydro-4H-imidazol-4-one skeleton by treatment of a halogenated derivative with low-boiling dimethylamine at a high temperature and pressure. The corresponding aliphatic ethers are usua
- Khan, Shahnawaz,Tyagi, Vikas,Mahar, Rohit,Bajpai, Vikas,Kumar, Brijesh,Chauhan, Prem M.S.
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p. 2405 - 2412
(2013/09/23)
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- A facile synthesis of functionalized dispirooxindole derivatives via a three-component 1,3-dipolar cycloaddition reaction
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An efficient synthesis of novel dispirooxindoles has been achieved through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the decarboxylative condensation of isatin and an α-amino acid with the dipolarophile 5-benzylid
- He, Jun,Ouyang, Guang,Yuan, Zhixiang,Tong, Rongsheng,Shi, Jianyou,Ouyang, Liang
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p. 5142 - 5154
(2013/06/27)
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- Synthesis and SAR-study for novel arylpiperazine derivatives of 5-arylidenehydantoin with α1-adrenoceptor antagonistic properties
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The study is focused on a series of 5-arylidenehydantoin derivatives with a phenylpiperazine-hydroxypropyl fragment at N3 of the hydantoin ring. The compounds were assessed on their affinity for α1-adrenoceptors and evaluated in functional bioassays for their antagonistic properties. Crystal structures of (Z)-5-(4-chlorobenzylidene)-3-(3-(4-(2-ethoxyphenyl)piperazin-1- yl)-2-hydroxypropyl)imidazolidine-2,4-dione (7) and hydrochloride of (Z)-5-(4-chlorobenzylidene)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl) propyl)imidazolidine-2,4-dione (10a) were solved using the X-ray diffraction method. Classical molecular mechanics (MMFFs force field, MCMM, MacroModel) were used to predict 3D structure of compounds 5a-18a using a crystal structure of 7. SAR analysis was performed on the basis of Barbaro's pharmacophore model and structural properties of previously investigated α1- adrenoceptor antagonists possessing a hydantoin fragment. Most of the compounds exhibited significant affinities for α1-ARs in nanomolar range (40-290 nM). The highest activities (Ki 1-affinities as follows: 3,4-di CH3O>2,4-di CH3O>4-Cl>2,3-di CH 3O>H>4-N(CH3)2.
- Handzlik, Jadwiga,Szymańska, Ewa,Wójcik, Renata,Dela, Anna,Jastrzebska-Wiesek, Magdalena,Karolak-Wojciechowska, Janina,Fruziński, Andrzej,Siwek, Agata,Filipek, Barbara,Kie?-Kononowicz, Katarzyna
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scheme or table
p. 4245 - 4257
(2012/08/28)
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- SnCl22H2O: An efficient reagent for selective and direct oxidative desulfurization of phenylmethylene-2-thiohydantoins to corresponding hydantoins
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A new and efficient protocol is presented for selective and direct oxidative conversion of phenylmethylene-2-thiohydantoins to corresponding hydantoins. It involves the use of SnCl2.2H2O, which oxidatively desulfurizes the phenylmeth
- Kumar, Ravi,Pandey, Shashi,Khan, Shahnawaz,Chauhan, Prem M. S.
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experimental part
p. 1404 - 1410
(2011/10/05)
-
- Synthesis and reactivity of 5-methylenehydantoins
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5-Methylenehydantoin, as well as the N-mono- and N,N-di-protected derivatives, can be obtained by different synthetic routes. These compounds can undergo a large variety of reactions, such as Diels-Alder, epoxidation, methanol addition and conjugate addition reactions of different types of nucleophiles, including carbon (cyanide), nitrogen (piperidine) and sulfur (thiols, thioacetate) nucleophiles. The reactivity with electrophilic reagents, such as m-CPBA or methanol in acidic medium, and the need for Lewis acids to promote the conjugate addition reactions indicate that hydantoin is a poor electron-withdrawing group.
- Fraile, José M.,Lafuente, Gustavo,Mayoral, José A.,Pallarés, Antonio
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experimental part
p. 8639 - 8647
(2011/11/30)
-
- Synthesis and antitumor evaluation of novel cyclic arylsulfonylureas: ADME-T and pharmacophore prediction
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Novel derivatives of 5-(substituted)benzylidene-3-(4-substituted)phenylsulfonylimidazolidine-2,4-diones (3a-r), 1-(4-substituted)phenylsulfonyl-3-(4-substituted)phenylpyrimidine-2,4,6-(1H,3H,5H)-triones (6a-l), and 3-(4-substituted)phenyl-1-(4-substituted)phenylsulfonylquinazoline-2,4(1H,3H)- diones (8a-l) have been synthesized and tested for their antitumor activity against 60 tumor cell lines taken from 9 different organs. The tested compounds have showed good inhibitory effect at the ovarian cancer (IGROV1) cell line. A significant inhibition for (RXF393) renal cancer cells was observed with series 3 compounds, while in the other two series 6 and 8, there was a significant inhibition of ovarian cancer cells (OVCAR-8) and melanoma cells (SK-MEL-2). Interestingly; beside the strong inhibition of compound 3q to IGROV1 and RXF393 cells, a great inhibition (199.62%) for (M14) Melanoma cells was observed at the tested concentration (10?μM). ADME-T and pharmacophore prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity.
- El-Deeb, Ibrahim M.,Bayoumi, Said M.,El-Sherbeny, Magda A.,Abdel-Aziz, Alaa A.-M.
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scheme or table
p. 2516 - 2530
(2010/07/05)
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- Synthesis and in vitro anticancer activity of 2,4-azolidinedione-acetic acids derivatives
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The synthesis and evaluation of anticancer activity of 2,4-thia(imida)zolidinedione-3- and 5-acetic acids amides were described. The structures of compounds were determined by IR, 1H NMR, and MS analysis. In vitro anticancer activity of these compounds has been tested in National Cancer Institute (NCI) and the relationships between structure and anticancer activity are discussed. Among 2,4-azolidinedione-acetic acids derivatives 2-[5-(4-chlorobenzylidene)-2,4-dioxo-imidazolidin-3-yl]-N-(2-trifluoromethyl-phenyl)-acetamide (Ic) was superior to other related compounds in terms of high selectivity for the leukemia CCRF-CEM (log GI50 = -6.06), HL-60(TB) (log GI50 = -6.53), MOLT-4 (log GI50 = -6.52) and SR (log GI50 = -6.51) cell lines.
- Kaminskyy, Danylo,Zimenkovsky, Borys,Lesyk, Roman
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scheme or table
p. 3627 - 3636
(2009/12/04)
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- Reactions of 5-arylidene-2-thiohydantoins with halogenated compounds and anthranilic acid
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5-arylidene-2-thiohydantoins 1a-c react with ethyl α-chloroacetate 2 and monochloroacetone to give the respective 2-imidazolinones 3a-c and 2-acetonylmercaptohydantoins 9a-c. Compounds 3a-c react with benzenediazonium chloride to afford hydrazones 5a-c. T
- Magd El-Din, Asmaa A.,Elsharabasy, Salwa A.,Hassan, Aisha Y.
-
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- Microwave-assisted solvent-free regiospecific synthesis of 5-alkylidene and 5-arylidenehydantoins
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Hydantoins have become a well-known class of structures that have found significant applications as agrochemicals and therapeutics. This structural motif is of interest in the synthesis of small building blocks suitable for the preparation of potentially
- Lamiri,Bougrin,Daou,Soufiaoui,Nicolas,Giralt
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p. 1575 - 1584
(2007/10/03)
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- Anticonvulsant Activity of Phenylmethylenehydantoins: A Structure-Activity Relationship Study
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Phenylmethylenehydantoins (PMHs) and their des-phenyl analogues were synthesized and evaluated for anticonvulsant activity using the maximal electroshock seizure (MES) assay. The phenyl rings of PMHs were substituted with a wide spectrum of groups, and th
- Thenmozhiyal, Jeyanthi Chinnappa,Wong, Peter Tsun-Hon,Chui, Wai-Keung
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p. 1527 - 1535
(2007/10/03)
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- Synthesis, reactions and conformational analysis of 5-arylidene-2-thiohydantoins as potential antiviral agents
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(Z)-5-Arylidene-1-(4-methylphenylsulfonyl)-2-thiohydantoins 5a,b were synthesized from the direct condensation of the aromatic aldehydes 4a,b with 1-(4-methylphenylsulfonyl)-2-thiohydantoins 3a,b. Compounds 5a,b were coupled with 2′-deoxy-3′,5′-di(4-methylbenzoyl)-α-D-erythro-pentofura nosyl chloride 6 under alkaline conditions to afford N3-protected nucleosides 7a,b. Reaction of 5a,b with chloromethyl methyl sulfide and/or 2-bromoacetaldehyde diethyl acetal in alkaline medium afforded N3-alkyl derivatives 8a-c. Reaction of 5a with 1,2-dichloroethane in alkaline conditions afforded bis-thiohydantoinylethane 9a,b. Compounds 5a,b were condensed with formaldehyde and secondary amines to afford 3-aminomethyl-2-thiohydantoins derivatives 10a-d. On the other hand, reaction of unsubstituted 2-thiohydantoins derivatives 11b,c with chloromethyl methyl sulfide afforded the mono- and bis-methylthio derivatives 12a,b and 13a,b, respectively. Reaction of 11b,c with secondary amines and formaldehyde gave 3-aminomethyl-2-thiohydantoins 14a-e. Reaction of 11a-C with bromoacetaldehyde diethyl acetal yielded the S-alkyl derivatives 15a-c which can be hydrolysed with ethanolic hydrochloric acid to afford 5-arylidenehydantoins 16a-c. The compounds do not display any antiviral activity.
- Khodair,El-Barbary,Abbas,Imam
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p. 261 - 278
(2007/10/03)
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- Humic substances as catalysts m condensation reactions
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Humic substances (HS) demonstrate appreciable impact on the rate of the condensation reactions as shown in the example of the reaction between hydrazine and 4-(dimethylamino)-benzaldhyde in an aquatic environment. The catalytic activity of HS has also been demonstrated in Knoevenagel and Claisen-Schmidt reactions for condensation of carbonyl compounds with CH acids. The aquatic fulvic acids are the most active in these reactions. The velocity of the studied reactions also depends on pH, temperature, the concentration and origin of HS used. A possible micellar and acid-base catalysis mechanism in aquatic media has been suggested.
- Klavins, Maris,Dipane, Judite,Babre, Kristine
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p. 737 - 742
(2007/10/03)
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- Synthesis of isotopically labelled L-phenylalanine and L-tyrosine
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A synthetic route to stable-isotope-substituted L-phenylalanine is presented, which allows the introduction of 13C, 15N, and deuterium labels at any position or combination of positions. For labelling of the aromatic ring, a synthetic route to ethyl benzoate (or benzonitrile) has been developed, based on the electrocyclic ring-closure of a 1,6-disubstituted hexatriene system, with in situ aromatization by elimination of one (amino) substituent. Several important (highly isotopically enriched) synthons have been prepared, namely benzonitrile, benzaldehyde, ethyl benzoate, and ethyl diphenyloxyacetate. Labelled L-phenylalanines have been synthesized from both aromatic precursors by initial conversion into sodium phenylpyruvate and subsequent transformation of this intermediate into the L-α-amino acid by an enzymatic reductive amination reaction. In this manner, highly enriched phenylalanines are obtained on the 10-gram scale and with high enantiomeric purities (≥ 99% ee). The method has been validated by the synthesis of [1'13C]-L-Phe and [2-D]-L-Phe. In addition, two methods are described for the introduction of isotopes into L-tyrosine starting from the isotopically enriched precursors benzonitrile and ethyl benzoate.
- Raap, Jan,Nieuwenhuis, Saskia,Creemers, Alain,Hexspoor, Sander,Kragl, Udo,Lugtenburg, Johan
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p. 2609 - 2621
(2007/10/03)
-
- Gas/Solid Reactions with Nitrogen Dioxide
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Numerous gas/solid reactions of nitrogen dioxide with organic substrates are investigated preparatively and mechanistically.Gaseous NO2 reacts with crystalline stable free radicals (nitroxyls 1, verdazyl 6) by electron transfer.The nitrite ions formed are irreversibly oxidized by NO2 via oxygen atom transfer.Solid cation nitrates are formed quantitatively.Thione bonds of thiohydantoins 8 are transformed to carbonyl bonds with formation of sulfur and NO presumably via nitrites as intermediates.Hydantoin 13 oxygenates at its free 5-methylene group via C-H abstraction and nitrite or it undergoes N-1 nitration via N-H abstraction depending on the conditions.Both reactions proceed quantitatively. 1,3-Oxazolidin-2-one (15) gives N-nitration and N-nitrosation with the NO produced.Nonenolized crystalline barbituric acids 17 are quantitatively nitrated (C-N bond formation with radicals) at their methylene groups. 4-Hydroxybenzaldehyde (19) and vanilline (22) give quantitative aromatic nitration (C-N bond formation with arenes) without melting.All possible regioisomers are formed.Solid 9-methylanthracene (26) gives a quantitative yield of its 10-nitro derivative 27.Crystalline anthracene (28) and gaseous NO2 yield 3 primary products 29 (cis; trans) and the new dimeric product 30 as well as the stable secondary products 31 and 32.The gas/solid tetranitration of tetraphenylethylene (33) is severely hindered by the water of reaction.However, a 95percent yield of pure tetrakis(p-nitrophenyl)ethylene is obtained if the drying agent MgSO4*2H2O is admixed and the product 34 extracted.The gas/solid procedures avoid solvents and fuming nitric acid.They give pure products without necessity for recrystallization in most cases and they avoid wastes.Atomic force microscopy (AFM) measurements on prominent faces of single crystals of 1a, 11a, 28, and 33 reveal phase rebuildings with well-directed long-range molecular transport.Nanoliquids were only present on (110) of 28.The characteristic AFM features are correlated with known X-ray crystal structure data and compared with previous results.The shape of the features depends on the molecular packing in the crystal bulk and on the molecular shapes.Molecular interpretations of the AFM features are given.
- Kaupp, Gerd,Schmeyers, Jens
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p. 5494 - 5503
(2007/10/02)
-
- α-Isocyanatoacrylonitriles from alkylidene- or arylidenecyanoacetic acids; synthesis and reactions
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The Curtius reaction converts alkylidene- or arylidenecyanoacetic acids to α-isocyanatoacrylonitriles in a stereospecific way. These versatile intermediates allow an easy access to arylacetic acids and various amino acid derivatives, as well as β-lactams or 2-azabutadienes.
- Jaafar,Francis,Danion-Bougot,Danion
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- Process for the preparation of monohydrated sodium phenylpyruvate
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A process for the preparation of monohydrated sodium phenylpyruvate comprises reacting benzaldehyde with the stoichiometric quantity of hydantoin in the aqueous medium in the presence of a catalytic quantity of a primary or secondary amine at high tempera
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-
- Hydantoin Analogues of Thymidine
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Hydantoin nucleosides were synthesized from a protected methyl 2-deoxy-D-ribofuranoside in a Friedel-Crafts catalyzed silyl-Hilbert-Johnson reaction as modified by Vorbrueggen.Atypical byproducts are accounted for by assuming the initial step being a ring opening of the sugar to give an acyclic glycos-1-yl cation.
- El-Barbary, Ahmed A.,Khodair, Ahmed I.,Pedersen, Erik B.
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p. 5994 - 5999
(2007/10/02)
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- Diethyl 2,4-Dioxoimidazolidine-5-phosphonates: Horner-Wadsworth-Emmons Reagents for the Mild and Efficient Preparation of C-5 Unsaturated Hydantoin Derivatives
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The phosphonates 19 and 20 were prepared from hydantoin and 1-methylhydantoin, respectively, by way of bromination at C-5 and a subsequent Michaelis-Arbuzov reaction with triethyl phosphite.The Horner-Wadsworth-Emmons-type reagents 19 and 20 were found to react readily with aromatic and aliphatic aldehydes, in the presence of a base, to produce C-5 unsaturated hydantoin derivatives 22 and 26, generally in high yield.The products 22 and 26 were frequently isolated as mixtures of E and Z isomers depending upon the identity of the aldehyde and phosphonate.The isomeric configuration of the products was determined from analysis of NMR spectral data.Long-range (13)C-(1)H coupling constants between the C-4 carbonyl of the hydantoin ring and the olefinic proton were found to be diagnostic of isomer geometry.Conditions were also developed that allowed coupling of 19 and 20 with cyclic and acyclic ketones and α-dicarbonyl compounds to afford the corresponding olefinic products.C-5 unsaturated hydantoin derivatives are of synthetic utility as precursors to α-amino acid derivatives, pyruvates, and the imidazoquinolin-2-one heterocyclic ring system, a class of potent inhibitors of low Km cAMP phosphodiesterase and the chromophore present in the siderophore azotobactin.
- Meanwell, Nicholas A.,Roth, Herbert R.,Smith, Edward C. R.,Wedding, Donald L.,Wright, J. J. Kim
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p. 6897 - 6904
(2007/10/02)
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- REACTIONS WITH 2-THIOHYDANTOIN DERIVATIVES: SYNTHESIS OF MANNICH BASES AND IMIDAZOTHIAZOLE DERIVATIVES
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5-Arylidene-2-thiohydantoins (1a-c) and 5-arylazo-1-phenyl-2-thiohydantoins (7a,b) were condensed with formaldehyde and primary or secondary aromatic amines to give the corresponding Mannich bases (2a-f) and 8a, b) respectively, which could also be conver
- Abdelaziz, Mahfouz A.,Riad, Bahia Y.
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p. 303 - 309
(2007/10/02)
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- Thermal Equilibration of Z- and E-Isomers of 5-Arylmetylenehydantoins. Evidence for Non-bonded Aromatic ?...Methyl Attractions
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Standard free energy differences between the Z- and E-isomers of 14 5-arylmethylenehydantoins have been estimated by thermal equilibration in dimethyl sulphoxide.The Z-configuration is more stable for the N-substituted compounds while the E-configuration is preferred for those N-1 methyl derivatives with only para-substituents in the aryl group.The ΔG0 values vary with the nature of the para substituents.For those N-1 methyl derivatives with two ortho-substituents in the aryl group, the configurational preference is dependent on the electronic effects of these aryl subtituents, suggesting the presence of non-bonded aromatic ?...Me interactions.The factors influencing the relative stabilities of Z- and E-isomers are discussed.
- Tan, Sau-Fun,Ang, Kok-Peng,How, Gee-Fung
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p. 2045 - 2050
(2007/10/02)
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- Reactions of Some 1,3-Diaminonucleophiles with Azlactones
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Triethylamine-mediated reactions of S-substituted isothiuronium halides (2) with unsaturated azlactones (1) gave the corresponding S-substituted 2-thiopyrimidines (3), S-substituted 3-thioacrylanilide (10), and 4-benzylidene-2-iminoimidazolidin-5-one (13)
- Tikdari, Ahmad M.,Tripathy, Pradeep K.,Mukerjee, Arya K.
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p. 1659 - 1662
(2007/10/02)
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- REACTIONS OF CHLOROSULFONYLBENZYLIDENE HYDANTOINS
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5-(Benzylidene- and o-chlorobenzylidene-) and cinnamylidene-hydantoins reacted with chlorosulfonic acid to give the corresponding p-sulfonyl chlorides (1, 35, 44).These were converted into 49 derivatives by reaction with amines, hydrazines and azide ion.
- Cremlyn, Richard,Jethwa, Sanjay,Joiner, Graham,White, David
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- Process for production of hydantoin derivatives
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Hydantoin derivatives are industrially advantageously produced at a high yield by reacting hydantoin with carbonyl compounds in the presence of (i) amino acids or the salts thereof and (ii) inorganic alkali compounds for a relatively short reaction time in an aqueous medium.
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- Process for the preparation of D1-β-aryl amino acids
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The invention relates to a process for the preparation of DL-β-aryl-amino acids of the general Formula STR1 wherein R, R1 and R2 stand for hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, nitro or C1-4 dialkylamino; whereby in the case of monosubstituted derivatives R and R1 are hydrogen and R2 has the same meaning as stated above and can be attached to position 2, 3 or 4 related to the methylene group; in the case of disubstituted derivatives R is hydrogen and R1 and R2 have the same meaning as stated above and are attached to positions 2,3; 2,4; 2,5; 2,6; 3,4 or 3,5 related to the methylene group; in the case of trisubstituted derivatives R, R1 and R2 have the same meaning as stated above and are attached to positions 2,3,4; 2,3,5; 2,3,6; 3,4,5 or 3,4,6 related to the methylene group.
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- REACTIONS OF 5-ARYLIDENE-2-THIOHYDANTOINS, SYNTHESIS OF NEW CONDENSED IMIDAZOTHIAZOLES
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5-Arylidene-2-thiohydantioins reacted with 2-bromopropionic acid or ethyl 2-bromobutanoate and phenacyl bromide yielded corresponding S-substituted mercapto acids or esters and S-phenacyl derivatives, respectively.Cyclization of these compounds resulted i
- Daboun, Hamed A.,Abdel-Fattah, A. M.,Hussein, M. M.,Shalaby, A. F. A.
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p. 1001 - 1007
(2007/10/02)
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- Process for the production of 5-arylidene hydantoins (B)
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5-Arylidene hydantoins are produced by condensation of an aromatic aldehyde with hydantoin in the presence of at least one ammonium salt of an aliphatic or aromatic carboxylic acid. The desired 5-arylidene hydantoins are obtained in high yields.
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- The Preparation and Reactions of 2-Benzyloxy-4-benzylideneoxazol-5-one
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The preparation of the title coumpound (4) and a survey of its chemistry are described.Its reactivity towards nucleophiles at C-5 is high compared with that of the corresponding 2-phenyl compound (1), and nucleophilic reagents attact (4) exclusively at th
- Jones, John H.,Witty, Michael J.
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p. 858 - 864
(2007/10/02)
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