3530-82-3Relevant articles and documents
Pd-Catalysed oxidative carbonylation of α-amino amides to hydantoins under mild conditions
Botla, Vinayak,Carfagna, Carla,Della Ca, Nicola,Gabriele, Bartolo,Maestri, Giovanni,Mancuso, Raffaella,Montanari, Luca,Motti, Elena,Voronov, Aleksandr
supporting information, p. 294 - 297 (2022/01/06)
The first example of palladium-catalysed oxidative carbonylation of unprotected α-amino amides to hydantoins is described here. The selective synthesis of the target compounds was achieved under mild conditions (1 atm of CO), without ligands and bases. The catalytic system overrode the common reaction pathway that usually leads instead to the formation of symmetrical ureas.
Identification of a New Zinc Binding Chemotype by Fragment Screening
Chrysanthopoulos, Panagiotis K.,Mujumdar, Prashant,Woods, Lucy A.,Dolezal, Olan,Ren, Bin,Peat, Thomas S.,Poulsen, Sally-Ann
, p. 7333 - 7349 (2017/09/22)
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.
Facile One-Pot Synthesis of Substituted Hydantoins from Carbamates
Tanwar, Dinesh Kumar,Ratan, Anjali,Gill, Manjinder Singh
supporting information, p. 2285 - 2290 (2017/10/06)
A novel and simple approach for the preparation of 3-substituted, 5-substituted, or 3,5-disubstituted hydantoins is reported. It involves the reaction of α-amino methyl ester hydrochlorides with carbamates to yield the corresponding ureido derivatives, which subsequently cyclize under basic conditions to produce substituted hydantoins in good yields. By applying this method, the bioactive anticonvulsant drug ethotoin was synthesized in good yield. The process avoids conventional multistep protocols and does not use the hazardous, irritant, toxic, or moisture-sensitive reagents, such as isocyanates or chloroformates, that are commonly used for the synthesis of these important compounds.
Method for preparing 5-substituted chiral hydantoin
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Paragraph 0017; 0018, (2017/02/28)
The invention discloses a method for directly preparing a 5-substituted chiral hydantoin compound by asymmetric catalyzing and hydrogenating of hydantoin-derived exocycloolefin. A chemical structural formula of the 5-substituted chiral hydantoin compound is expressed by a formula (I) shown in the description. A chemical reaction equation is shown in the description, wherein a compound (II) is the hydantoin-derived exocycloolefin; a compound (III) is a catalyst, and the catalyst is a metal compound of chiral diphosphine ligand. Compared with the prior art, the method has the characteristics that the chiral multiplication is realized, the efficiency and selectivity are high, the atom economy is realized, the green and non-pollution effects are realized, the industrialization is easy, and the like.
A Sustainable, Semi-Continuous Flow Synthesis of Hydantoins
Vukeli?, Stella,Koksch, Beate,Seeberger, Peter H.,Gilmore, Kerry
, p. 13451 - 13454 (2016/09/13)
Hydantoins are an important class of heterocycles with applications in pharmacy, agriculture, and as intermediates in organic synthesis. Traditional synthetic procedures to access hydantoins are target oriented with multiple synthetic steps and often use reagents that are not commercially available or sustainable. Herein, an efficient process is described for accessing hydantoins starting from commercially available amines using consecutive gas–liquid transformations (oxygen, carbon dioxide). This semi-continuous process produced ten benzylic/aliphatic hydantoins in good overall yields (52–84 %).
Continuous Synthesis of Hydantoins: Intensifying the Bucherer-Bergs Reaction
Monteiro, Julia L.,Pieber, Bartholom?us,Corrêa, Arlene G.,Kappe, C. Oliver
supporting information, p. 83 - 87 (2015/12/26)
A continuous Bucherer-Bergs hydantoin synthesis utilizing intensified conditions is reported. The methodology is characterized by a two-feed flow approach to independently feed the organic substrate and the aqueous reagent solution. The increased interfacial area of the biphasic reaction mixture and the lack of headspace enabled almost quantitative conversions within ca. 30 minutes at 120 °C and 20 bar even for unpolar starting materials. In addition, a selective N(3)-monoalkylation of the resulting heterocycles under batch microwave conditions is reported yielding potential acetylcholinesterase inhibitors.
Use of the hydantoin isostere to produce inhibitors showing selectivity toward the vesicular glutamate transporter versus the obligate exchange transporter system
Ahmed, S. Kaleem,Etoga, Jean-Louis G.,Patel, Sarjubhai A.,Bridges, Richard J.,Thompson, Charles M.
scheme or table, p. 4358 - 4362 (2011/08/06)
Evidence was acquired prior to suggest that the vesicular glutamate transporter (VGLUT) but not other glutamate transporters were inhibited by structures containing a weakly basic α-amino group. To test this hypothesis, a series of analogs using a hydantoin (pKa ～ 9.1) isostere were synthesized and analyzed as inhibitors of VGLUT and the obligate cystine-glutamate transporter (system xc-). Of the hydantoin analogs tested, a thiophene-5-carboxaldehyde analog 2l and a bis-hydantoin 4b were relatively strong inhibitors of VGLUT reducing uptake to less than 6% of control at 5 mM but few inhibited system xc- greater than 50% of control. The benzene-2,4-disulfonic acid analog 2b and p-diaminobenzene analog 2e were also good hydantoin-based inhibitors of VGLUT reducing uptake by 11% and 23% of control, respectively, but neither analog was effective as a system xc- inhibitor. In sum, a hydantoin isostere adds the requisite chemical properties needed to produce selective inhibitors of VGLUT.
New generation of enantiomerically pure N-α-carboxyalkylglycolurils
Baranov, Vladimir V.,Kravchenko, Angelina N.,Belyakov, Pavel A.,Makhova, Nina N.
, p. 96 - 98 (2008/12/20)
The title compounds have been synthesised by the α-ureidoalkylation of (S)-N-carbamoyl-α-amino acids with 1,3-dimethyl- and 1,3-dimethyl-4,5-diphenyl-4,5-dihydroxyimidazolidin-2-ones.
Microwave-assisted solid-phase synthesis of hydantoin derivatives
Colacino, Evelina,Lamaty, Frédéric,Martinez, Jean,Parrot, Isabelle
, p. 5317 - 5320 (2008/02/09)
A microwave-assisted synthesis of 3,5- and 1,3,5-substituted hydantoins starting from various resins for solid-phase combinatorial chemistry has been developed. The hydantoins were synthesized from pre-loaded resins with amino acids via treatment with isocyanate or phenylisocyanate and subsequent intramolecular cyclization. Both reactions were performed under microwave irradiation. We studied the cyclative cleavage leading to hydantoin compounds dependent on the nature of the amino acid and the nucleofuge properties of the resin.
Potent and specific inhibition of human leukocyte elastase, cathepsin G and proteinase 3 by sulfone derivatives employing the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold
Groutas, William C.,Kuang, Rongze,Ruan, Sumei,Epp, Jeffrey B.,Venkataraman, Radhika,Truong, Tien M.
, p. 661 - 671 (2007/10/03)
This paper describes the results of structure-activity relationship studies in a series of heterocyclic mechanism-based inhibitors based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold I and capable of interacting with the S(n) and S(n)' subsites of a serine proteinase. Sulfone derivatives of I were found to be highly effective, time-dependent inhibitors of human leukocyte elastase (HLE), cathepsin G (Cat G) and proteinase 3 (PR 3). The judicious selection of an R1 group (accommodated at the primary specificity site S1) that is based on the known substrate specificity of a target serine proteinase, was found to yield highly selective inhibitors. The presence of a benzyl group (R2=benzyl) at the S2 subsite was found to lead to a pronounced enhancement in inhibitory potency. Furthermore, the effective use of computer graphics and modeling has led to the design of potent, water-soluble inhibitors. The results of these studies demonstrate that the 1,2,5-thiadiazolidin-3-one 1,1, dioxide platform provides an effective means for appending recognition elements in a well-defined vector relationship, and in fashioning highly-selective and potent inhibitors of serine proteinases. Copyright (C) 1998 Elsevier Science Ltd.
