pinecone/core-2020-05-10-deduplication huggingface dataset:
(Tetracycline)europium(III) Complex as Luminescent Probe for Hydrogen Peroxide Detection

Luminescence spectra of aqueous solutions containing a fixed concentration of tetracycline (TC) and increasing concentrations of Eu3+ were recorded both in the absence and presence of hydrogen peroxide (H2O2). In H2O2-free solutions in which the Eu/TC molar ratio was varied from 1 : 1 to 8 : 1, the 5D0 --> 7F0 transition consisted of only one peak at 580 nm. In the presence of H2O2, an extra peak appeared in the spectrum at 578 nm when the Eu/TC molar ratios were above 2.5. A detailed analysis of this spectral region revealed that at lower Eu/TC molar ratios (up to 2 : 1), the 5D0 --> 7F0 transition experienced a slight blue shift. This indicates that at low Eu/TC molar ratios, the presence of H2O2 leads to two different environments of the trivalent europium ions, which most likely form bridged peroxide complexes with hydrogen peroxide (mu-H2O2 ligand). Luminescence spectra measured in the presence of molybdate ions, which catalytically decompose H2O2, led to the disappearance of the extra europium(III) site that was formed in the presence of H2O2. The intensity of the hypersensitive 5D0 --> 7F2 transition did not linearly depend on the H2O2/TC molar ratio. For H2O2/TC ratios up to 10, a sharp linear increase of the peak intensity was observed, but with further increase of the H2O2 concentration, the intensity remained nearly constant. For H2O2/TC ratios above 100, the intensity of this transition even started to decrease, which limits the use of the (tetracycline)europium(III) system to quantify hydrogen peroxide in solution.status: publishe
Synthesis of 1,3-Selenazol-2(3H)-imines

The reaction of N,N’-diarylselenoureas 16 with phenacyl bromide in EtOH under reflux, followed by treatment with NH3 , gave N,3-diaryl-4-phenyl-1,3-selenazol-2(3H)-imines 13 in high yields (Scheme 2). A reaction mechanism via formation of the corresponding Se-(benzoylmethyl)isoselenoureas 18 and\ud
subsequent cyclocondensation is proposed (Scheme 3). The N,N’-diarylselenoureas 16 were conveniently prepared by the reaction of aryl isoselenocyanates 15 with 4-substituted anilines. The structures of 13a and 13c were established by X-ray crystallography
Tri- and Tetra-Substituted N-Phthalimidoaziridines in 1,3-Dipolar Cycloaddition Reactions

The thermal reactions of the 2,2,3-tri-substituted 1-phthalimidoaziridine 1a with dimethyl acetylenedicarboxylate (DMAD), thioketones 4a – 4d, and dimethyl azodicarboxylate (5) proceed even at room temperature leading to the five-membered cycloadducts 2a, 6 – 8, and 12, respectively, with retention of the spatial arrangement of the aziridine substituents, in contrast to the expectation based on the conservation of orbital symmetry in concerted reactions. The analogous reactions of the tetra-substituted phthalimidoaziridine 1b with thioketones at 40° lead to the 1,3-thiazolidine derivatives 10 and 11 as mixtures of diastereoisomers. These unexpected results may be explained by either the isomerization of the intermediate azomethine ylides or a non-concerted stepwise cycloaddition of these ylides with the dipolarophiles. The structures of some adducts have been determined by X-ray crystallography
Synthesis of Three-, Five-, and Six-Membered Heterocycles Derived from New β-Amino-α-trifluoromethyl Alcohols

Nucleophilic trifluoromethylation of α-iminoketones 2, derived from arylglyoxal, with Ruppert-Prakash reagent (CF3SiMe3) offers a convenient access to the corresponding O-silylated β-imino-α-trifluoromethyl alcohols. In a ‘one-pot’ procedure, by treatment with NaBH4, these products smoothly undergo reduction and desilylation yielding the expected β-amino-α-trifluoromethyl alcohols 4. The latter were used as convenient starting materials for the synthesis of diverse trifluoromethylated heterocycles, including aziridines 5, 1,3-oxazolidines 8, 1,3-oxazolidin-2-ones 9, 1,3,2-oxazaphospholidine 2-oxides 10, 1,2,3-oxathiazolidine 2-oxides 11, and morpholine-2,3-diones 12. An optically active 5-trifluoromethyl-substituted 1,3-oxazolidin-2-one 9g was also obtained
Synthesis and Crystal Structure of 3,3,6,6-Tetramethylmorpholine-2,5-dione, and its 5-Monothio- and 2,5-Dithio-Derivatives

The synthesis of 3,3-dimethylmorpholine-2,5-diones 4a was achieved conveniently via the ‘direct amide  cyclization’ of the linear precursors of type 3, which were prepared by the coupling of 2,2-dimethyl-2H-azirin-3-amines 2 with 2-hydroxyalkanoic acids 1. Thionation of 4a with Lawesson’s reagent yielded the corresponding 5-thioxomorpholin-2-ones 10 and morpholine-2,5-dithiones 11, respectively, depending on the reaction conditions. The structures of 3aa, 4aa, 10a and 11a were established by X-ray crystallography. All attempts to prepare S-containing morpholine-2,5-dione analogs or thiomorpholine-2,5-diones by cyclization of corresponding S-containing precursors were unsuccessful and led to various other products. The structures of some of them have also been established by X-ray crystallography
Reaction of optically active Oxiranes with Thiofenchone and 1-Methylpyrrolidine-2-thione. Formation of 1,3-Oxathiolanes and Thiiranes

The SnCl4-catalyzed reaction of (-)-thiofenchone (= 1,3,3-trimethyl-bicyclo[2.2.1]heptane-2-thione;10) with (R)-2-phenyloxirane ((R)-11) in anhydrous CH2Cl2 at  -60° led to two spirocyclic, stereoisomeric\ud
4-phenyl-1,3-oxathiolanes 12 and 13 via a regioselective ring enlargement, in accordance with previously reported reactions of oxiranes with thioketones (Scheme 3). The structure and configuration of the major isomer 12 were determined by X-ray crystallography. On the other hand, the reaction of 1-\ud
methylpyrrolidine-2-thione (14a) with (R)-11 yielded stereoselectively (S)-2-phenylthiirane ((S)-15) in 56% yield and 87 –93% ee, together with 1-methylpyrrolidin-2-one (14b). This transformation occurs via an SN2-type attack of the S-atom at C(2) of the aryl-substituted oxirane and, therefore, with inversion of the configuration (Scheme 4). The analogous reaction of 14a with (R)-2-{[(triphenylmethyl)oxy]methyl}oxirane ((R)-16b) led to the corresponding (R)-configured thiirane (R)-17b (Scheme 5); its structure and configuration were also determined by X-ray crystallography. A mechanism via initial ring opening by attack at C(3) of the alkyl-substituted oxirane, with retention of the configuration, and subsequent decomposition of the formed 1,3-oxathiolane with inversion of the configuration is proposed (Scheme 5)
Synthesis of Poly-Aib Oligopeptides and Aib-Containing Peptides via the 'Azirine/Oxazolone Method', and their crystal structures

The protected poly-Aib oligopeptides Z-(Aib)n-N(Me)Ph with n = 2 – 6 were prepared according to the 'azirine/oxazolone method', i.e., by coupling amino or peptide acids with 2,2,N-trimethyl-N-phenyl-2H-azirin-3-amine (1a) as an Aib synthon (Scheme 2). Following the same concept, the segments Z-(Aib)3-OH (9) and H-L-Pro-(Aib)3-N(Me)Ph (20) were synthesized, and their subsequent coupling with N,N’-dicyclohexylcarbodiimide (DCC)/ZnCl2 led to the protected heptapeptide Z-(Aib)3-L-Pro-(Aib)3-N(Me)Ph (21; Scheme 3). The crystal structures of the poly-Aib oligopeptide amides were established by X-ray crystallography confirming the 310-helical conformation of Aib peptides
Reactions of Imidoyl Isoselenocyanates with Aromatic 2-Amino N-Heterocycles and 1-Methyl-1H-imidazole

The reaction of N-phenylimidoyl isoselenocyanates 1 with 2-amino-1,3-thiazoles 10 in acetone proceeded smoothly at room temperature to give 4H-1,3-thiazolo[3,2-a] [1,3,5]triazine-4-selones 13 in fair yields (Scheme 2). Under the same conditions, 1 and 2-amino-3-methylpyridine (11) underwent an addition reaction, followed by a spontaneous oxidation, to yield the 3H-4l4-[1,2,4]selenadiazolo[1’,5’:1,5] [1,2,4]selenadiazolo[2,3-a]pyridine 14 (Scheme 3). The structure of 14 was established by X-ray crystallography (Fig. 1). Finally, the reaction of 1-methyl-1H-imidazole (12) and 1 led to 3-methyl-1-(N-phenylbenzimidoyl)-1H-imidazolium selenocyanates 15 (Scheme 4). In all three cases, an initially formed selenourea derivative is proposed as an intermediate
Synthesis and selected reactions of hydrazides containing an imidazole moiety

The preparation of two types of imidazole derivatives bearing a hydrazide group was achieved by treatment of the corresponding esters with NH2NH2·H2O in MeOH at room temperature. In the case of 4-(ethoxycarbonyl)-1H-imidazole 3-oxides 3, hydrazides of type 1 were formed with retention of the N-oxide structure (Scheme 1). Interestingly, due to a strong H-bonding, no deoxygenation of the N-O function could be achieved even by treatment of 3 with Raney-Ni. The second type, 2-[(1H-imidazol-2-yl)sulfanyl]acetohydrazides 2, was obtained from 1H-imidazole-2(3H)-thiones 4 in two steps via S-alkylation with methyl bromoacetate, followed by treatment with NH2NH2·H2O (Scheme 2). An imidazole 7, containing both types of hydrazide groups, was prepared analogously from ethyl 2,3-dihydro-2-thioxo-1H-imidazole-4-carboxylate 4d (Scheme 4). Both types of hydrazides, 1 and 2, were transformed successfully to the corresponding acylhydrazones 8 and 9, respectively (Scheme 5). Furthermore,\ud
it has been shown that hydrazides of type 1 are useful starting materials for the synthesis of 1,2,4-triazole-3-thiones 11 and 1,3,4-thiadiazole-2-amines 12, bearing an imidazole 3-oxide moiety (Scheme 7)
Synthesis of Bis-Heterocyclic 1H-Imidazole 3-Oxides from 3-Oxido-1H-imidazole-4-carbohydrazides

The reaction of 1H-imidazole-4-carbohydrazides 1, which are conveniently accessible by treatment of the corresponding esters with NH2NH2·H2O, with isothiocyanates in refluxing EtOH led to thiosemicarbazides (= hydrazinecarbothioamides) 4 in high yields (Scheme 2). Whereas 4 in boiling\ud
aqueous NaOH yielded 2,4-dihydro-3H-1,2,4-triazole-3-thiones 5, the reaction in concentrated H2SO4 at room temperature gave 1,3,4-thiadiazol-2-amines 6. Similarly, the reaction of 1 with butyl isocyanate led to semicarbazides 7, which, under basic conditions, undergo cyclization to give 2,4-dihydro-3H-1,2,4-triazol-3-ones 8 (Scheme 3). Treatment of 1 with Ac2O yielded the diacylhydrazine derivatives 9 exclusively, and the alternative isomerization of 1 to imidazol-2-ones was not observed (Scheme 4). It is\ud
important to note that, in all these transformations, the imidazole N-oxide residue is retained. Furthermore, it was shown that imidazole N-oxides bearing a 1,2,4-triazole-3-thione or 1,3,4-thiadiazol-2-amine moiety undergo the S-transfer reaction to give bis-heterocyclic 1H-imidazole-2-thiones 11 by treatment with 2,2,4,4-tetramethylcyclobutane-1,3-dithione (Scheme 5)
A new alkylation method for heptalene-4,5-dicarboxylates and of one of their pseudoester forms

Dimethyl heptalene-4,5-dicarboxylates† undergo preferentially a Michael addition reaction at C(3) with α-lithiated alkyl phenyl sulfones at temperatures below −50°, leading to corresponding cis-configured 3,4-dihydroheptalene-4,5-dicarboxylates (cf. Table 1, Schemes 3 and 4). The corresponding heptalenofuran-1-one-type pseudoesters of dimethyl heptalene-4,5-dicarboxylates (Scheme 5) react with [(phenylsulfonyl)methyl]lithium almost exclusively at C(1) of the furanone group (Scheme 6). In contrast to this expected behavior, the uptake of 1-[phenylsulfonyl)ethyl]lithium occurs at C(5) of the heptalenofuran-1-ones as long as they carry a Me group at C(11) (Schemes 6 and 7). The 1,4- as well as the 1,6-addition products eliminate, on treatment with MeONa/MeOH in THF, benzenesulfinate, thus leading to 3- and 4-alkylated dimethyl heptalene-4,5-dicarboxylates, respectively (Schemes 8–13). The configuration of the addition reaction of the nucleophiles to the inherently chiral heptalenes is discussed in detail (cf. Schemes 14–19) on the basis of a number of X-ray crystal-structure determinations as well as by studies of the temperature-dependence of the 1H-NMR spectra of the addition products
Unexpected course of the reaction of 2-Unsubstituted 1H-Imidazole 3-Oxides with Ethyl Acrylate

The attempted ethenylation at C(2) of 2-unsubstituted 1H-imidazole N-oxides with ethyl acrylate (= prop-2-enoate) in the presence of Pd(OAc)2 does not occur. In contrast to the other aromatic N-oxides, the [2+3] cycloaddition of imidazole N-oxides predominates, and 3-hydroxyacrylates, isomeric with the cycloadducts, are key products for the subsequent reaction. The final products were identified as dehydrated 2+1 adducts of 1H-imidazole N-oxide and ethyl acrylate. The role of the catalyst is limited to the dehydration of the intermediate 3-hydroxypropanoates to give 1H-imidazol-2-yl-substituted acrylates
Novel Synthesis of 2-Alkylquinolizinium-1-olates and their 1,3-Dipolar Cycloaddition reactions with Acetylenes

Several 2-alkylquinolizinium-1-olates 9, i.e., heterobetaines, were prepared from ketone 11, the latter being readily available either from pyridine-2-carbaldehyde via a Grignard reaction, followed by oxidation with MnO2, or from 2-picolinic acid (= pyridine-2-carboxylic acid) via the corresponding Weinreb amide and subsequent Grignard reaction. Mesoionic heterobetaines such as quinolizinium derivatives have the potential to undergo cycloaddition reactions with double and triple bonds, e.g., 1,3-dipolar cycloadditions or Diels-Alder reactions. We here report on the scope and limitations of cycloaddition reactions of 2-alkylquinolizinium-1-olates 9 with electron-poor acetylene derivatives. As main products of the reaction, 5-oxopyrrolo[2,1,5-de]quinolizines (= '[2.3.3]cyclazin-5-ones') 19 were formed via a regioselective [2+3] cycloaddition, and cyclohexadienone derivatives, formed via a Diels-Alder reaction, were obtained as side products. The structures of 2-benzylquinolizinium-1-olate (9a) and two '[2.3.3]cyclazin-5-ones' 19i and 19l were established by X-ray crystallography
Synthesis of Aib-Pro Oligopeptides by repeated Azirine coupling with the Aib-Pro synthon

A new synthesis of (Aib-Pro)n oligopeptides (n = 2, 3, and 4) via azirine coupling by using the dipeptide synthon methyl N-(2,2-dimethyl-2H-azirin-3-yl)-l-prolinate (1b; Fig. 1) is presented. The most important feature of the employed protocol is that no activation of the acid component is necessary, i.e., no additional reagents are required, and the coupling reaction is performed under mild conditions at room temperature. As an attempt to provide an answer to the question of the preferred conformation of the prepared molecules, we carried out experiments by using NMR techniques and X-ray crystallography. For example, in the case of the hexapeptide 11, it was possible to compare the conformations in the crystalline state and in solution. After the selective hydrolysis of the methyl ester p-BrBz-(Aib-Pro)4-OMe (13) under basic conditions, the corresponding octapeptide acid was obtained, which was then converted into the octapeptide amide p-BrBz-(Aib-Pro)4-NHC6H13 (15) by using standard coupling conditions and activating reagents (HOBt/TBTU/DIEA) of the peptide synthesis. The conformation of this compound, as well as those of the tetrapeptides 14 and 18, was also established by X-ray crystallography and in solution by NMR techniques. In the crystalline state, a beta-bend ribbon structure is the preferred conformation, and similar conformations are formed in solution
New Optically Active Bis-Heterocycles Derived from (S)-Proline

Enantiomerically pure bis-heterocycles containing a (S)-proline moiety have been prepared starting from (S)-N-benzylprolinehydrazide (2b). The reactions with isothiocyanates or butyl isocyanate in refluxing MeOH led to the corresponding thiosemicarbazide 5 and semicarbazide 9 with a N-benzylprolinoyl residue. The structure of the tert-butyl derivative 5d was established by X-ray crystallography. Base-catalyzed cyclization of 5 and 9 led to (S)-3-(pyrrolidin-2-yl)-1H-1,2,4-triazole-5(4H)-thiones 6 and the corresponding 5(4H)-one 8, respectively, whereas, in concentrated H2SO4, compounds 5 undergo cyclization to give (S)-5-amino-2-(pyrrolidin-2-yl)-1,3,4-thiadiazoles 7. Furthermore, 2b reacted with hexane-2,5-dione in boiling iPrOH to yield the (S)-N-(2,5-dimethylpyrrol-1-yl) prolinamide 10. In the case of the bis-heterocycle 8, treatment with HCOONH4 and Pd/C in MeOH gave the debenzylated product 12
Clerodendrumic acid, a new Triterpenoid from Clerodendrum glabrum (Verbanaceae), and antimicrobial activities of fractions and constituents

One new triterpenoid, (3β,11α,19β)-3-(butanoyloxy)-11-hydroxytaraxast-20(30)-ene-23,28-dioic acid (clerodendrumic acid; 1) was isolated from the hexane extract of the leaves of Clerodendrum glabrum var. glabrum along with heptadecanoic acid (2). The structure of the new compound was elucidated by interpretation of its NMR (1D and 2D), MS, and IR data. Combined fractions C and D from the column chromatography of the hexane extract exhibited significant antifungal activities (average MIC of 0.10 mg/ml) against Candida albicans and Cryptococcus neoformans. C. albicans was relatively resistant to clerodendrumic acid (1; MIC 125 μg/ml) and was resistant to heptadecanoic acid (2; MIC 188 μg/ml). Both compounds had low antibacterial activities against two Gram-positive and two Gram-negative bacteria with average MIC values of 157 and 172 μg/ml, respectively. Compounds 1 and 2 were relatively nontoxic against monkey kidney Vero cells in vitro with IC50 values of 202.6 and 108.4 μg/ml, respectively.National Research Foundation (NRF) and the Netherlands Universities Foundation for International Cooperation (NUFFIC).http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1522-2675hb201
New selenosemicarbazides derived from imidazole-based carbohydrazides

Imidazole-based carbohydrazides, i.e., 3-oxidoimidazole-4-carbohydrazides 1 and 2-[(imidazol-2-yl)sulfanyl]acetohydrazides 6, react with aryl isoselenocyanates 4 in MeOH at room temperature to give the corresponding selenosemicarbazides 5 and 7, respectively, in good yields. On heating 7b in DMF in the presence of air to 100°, 1,3,4-oxadiazole 8a was formed via cyclization and formal elimination of H2Se. Product 8a was also obtained after heating of a mixture of 4a and 6b under the same conditions. On the other hand, on heating of a solution of 7c in MeOH at reflux, a cyclization occurred to give the corresponding 1,2,4-triazole-3-selone 9b. Again, the same product was formed when a mixture of 4b and 6b was heated in MeOH. Surprisingly, analogous cyclizations of selenosemicarbazides of type 5 under the same conditions failed, and only decomposition was observed. The structures of 7a, 7d, and 9b have been established by X-ray crystallography
Unexpected reaction course of 3-Amino-5-aryl-1H-pyrazoles with Dialkyl Dicyanofumarates

On treatment of 3-amino-5-aryl-1H-pyrazoles 1 with dialkyl dicyanofumarates (=(E)-but-2-enedioates) 4 in boiling 1,2-dichloroethane, two competitive reactions occurred leading to 3-aryl-5-cyano-6,7-dihydro-6-oxo-1H-pyrazolo[3,4-b]pyridine-4-carboxylates 10 and 7-amino-2-arylpyrazolo[1,5-a]pyrimidine-5,6-dicarboxylates 11. In DMF at room temperature, as well as at 100°, only compounds 10 were isolated. The formation of the major products of type 10 was rationalized via Michael addition of 1 as a C(4)-nucleophile onto 4, followed by HCN elimination and lactamization. On the other hand, the minor products 11 result from a Michael addition of 1 onto 4 via the NH2 group, and subsequent HCN\ud
elimination and cyclization. The structures of the products have been established by X-ray crystallography
Insights into the Synthesis of Steroidal A-Ring Olefins

one (5), from the D1-3-keto enone, (5a,17b)-3-oxo-5-androst-1-en-17-yl acetate (1), through a strategy
involving the reaction of D1-3-hydroxy allylic alcohol, 3b-hydroxy-5a-androst-1-en-17b-yl acetate (2),
with SOCl2 , was revisited in order to prepare and biologically evaluate 5 as aromatase inhibitor for breast
cancer treatment. Surprisingly, the followed strategy also afforded the isomeric D2-olefin 6 as a byproduct,
which could only be detected on the basis ofNMR analysis. Optimization of the purification and
detection procedures allowed us to reach 96% purity required for biological assays of compound 5.
The same synthetic strategy was applied, using the D4-3-keto enone, 3-oxoandrost-4-en-17b-yl acetate
(8), as starting material, to prepare the potent aromatase inhibitor D4-olefin, androst-4-en-17-one (15).
Unexpectedly, a different aromatase inhibitor, the D3,5-diene, androst-3,5-dien-17-one (12), was formed.
To overcome this drawback, another strategy was developed for the preparation of 15 from 8. The data
now presented show the unequal reactivity of the two steroidal A-ring D1- and D4-3-hydroxy allylic
alcohol intermediates, 3b-hydroxy-5a-androst-1-en-17b-yl acetate (2) and 3b-hydroxyandrost-4-en-17byl
acetate (9), towards SOCl2 , and provides a new strategy for the preparation of the aromatase inhibitor
12. Additionally, a new pathway to prepare compound 15 was achieved, which avoids the formation of
undesirable by-products.The authors thank FCT (FundaÅa˜o para a Cieˆncia e Tecnologia) for the strategic project PEst-OE/
SAU/UI0177/2011. Carla Varela also thanks FCT for a Ph.D. fellowship (SFRH/BD/44872/2008). We
also acknowledge the Rede Nacional de RMN for access to the facilities. The Varian VNMRS 600 MHz
spectrometer is part of the National NMR Network and was purchased with in the framework of the
National Programme for Scientific Re-equipment, contract REDE/1517/RMN/2005, with funds from
POCI 2010 (FEDER) and (FCT). The work was also funded by FEDER Funds through the Operational
Competitiveness Program-COMPETE and by National Funds through FCT- FundaÅa˜o para a Cieˆncia e
Tecnologia under the project FCOMP-01 – 0124-FEDER-020970 (PTDC/QUI-BIQ/120319/2010). The
authors are also grateful to Laboratory of Mass Spectrometry (LEM) of the Node CEF/UC, integrated in
the National Mass Spectrometry Network (RNEM) of Portugal, for the MS analyses
Reactions of acid Chlorides/Ketenes with 2-substituted 4,5-Dihydro-4,4-dimethyl-1,3-thiazoles: Formation of Penam derivatives

Addition reactions of acid chlorides with various 2-substituted 4,5-dihydro-4,4-dimethyl-5-(methylsulfanyl)-1,3-thiazoles under basic conditions were studied. Two kinds of products were obtained from these additions, beta-lactams and non-beta-lactam adducts. When the reaction was carried out with 4,5-dihydro-1,3-thiazoles with a Ph substituent at C(2), the reaction proceeded via formal [2+2] cycloaddition and led to the correspoding beta-lactam. On the other hand, acid chlorides and 4,5-dihydro-1,3-thiazoles bearing an alpha-H-atom at the C(2)-substituent underwent C(alpha)- and/or N-addition reactions and furnished non-beta-lactam adducts, i.e., C(alpha)- and/or N-acylated 1,3-thiazolidines. The attempted transformations of sulfonyl esters of exo-6-hydroxy penams to endo-6-azido penams failed, although they were successful with mono-beta-lactams under the same conditions