- Ring Expansion of Thiolactams via Imide Intermediates: An Amino Acid Insertion Strategy
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The AgI-promoted reaction of thiolactams with N-Boc amino acids yields an N-(α-aminoacyl) lactam that can rearrange through an acyl transfer process. Boc-deprotection results in convergence to the ring-expanded adduct, thereby facilitating an overall insertion of an amino acid into the thioamide bond to generate medium-sized heterocycles. Application to the site-specific insertion of amino acids into cyclic peptides is demonstrated.
- Shang, Jing,Thombare, Varsha J.,Charron, Carlie L.,Wille, Uta,Hutton, Craig A.
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supporting information
p. 1620 - 1625
(2020/12/23)
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- Evaluation of thioamides, thiolactams and thioureas as hydrogen sulfide (H2S)donors for lowering blood pressure
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Hydrogen sulfide (H2S)is a biologically important gaseous molecule that exhibits promising protective effects against a variety of pathological processes. For example, it was recognized as a blood pressure lowering agent. Aligned with the need for easily modifiable platforms for the H2S supply, we report here the preparation and the H2S release kinetics from a series of structurally diversified thioamides, thiolactams and thioureas. Three different thionation methods based on the usage of a phosphorus pentasulfide and Lawesson reagent were applied to prepare the target thioamides and thiolactams. Furthermore, obtained H2S donors were evaluated both in in vivo and in vitro studies. The kinetic parameters of the liberating H2S was determined and compared with NaHS and GYY4137 using two different detection technics i.e.; fluorescence labeling 7-azido-4-methyl-2H-chromen-2-one and 5,5‘-dithiobis (2-nitrobenzoic acid), sulfhydryl probe, also known as the Ellman's reagent. We have proved that the amount of releasing H2S from these compounds is controllable through structural modifications. Finally, the present study shows a hypotensive response to an intravenous administration of the developed donors in the anesthetized rats.
- Zaorska, Ewelina,Hutsch, Tomasz,Gawry?-Kopczyńska, Marta,Ostaszewski, Ryszard,Ufnal, Marcin,Koszelewski, Dominik
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supporting information
(2019/04/29)
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- ASK1 INHIBITOR AND PREPARATION METHOD AND USE THEREOF
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The present disclosure relates to a compound as shown in formula (II), a tautomer or a pharmaceutically acceptable salt thereof, and disclosed is the use thereof in preparing a drug for treating an ASK1-associated disease.
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Paragraph 0183
(2020/01/02)
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- PYRIDINE DERIVATIVE AS ASK1 INHIBITOR AND PREPARATION METHOD AND USE THEREOF
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Disclosed in the present invention are a compound as shown in formula (II), a tautomer or a pharmaceutically acceptable salt thereof, and also disclosed is the use thereof in preparing a drug for treating an ASK1-associated disease.
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Paragraph 0086-0087
(2019/12/05)
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- A THIONATION PROCESS AND A THIONATING AGENT
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A process for transforming a group >C=O (I) in a compound into a group >C=S (II) or into a tautomeric form of group (II) in a reaction giving a thionated reaction product, by use of crystalline P2S5·2 C5H5N as a thionating agent. A thionating agent which is crystalline P2S5·2 C5H5N
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Page/Page column 13
(2012/08/27)
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- A thionation process and a thionating agent
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A process for transforming a group >C=O (I) in a compound into a group >C=S (II) or into a tautomeric form of group (II) in a reaction giving a thionated reaction product, by use of crystalline P2S5·2 C5H5N as a thionating agent. A thionating agent which is crystalline P2S5·2 C5H5N.
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Page/Page column 9
(2012/08/14)
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- Ruthenium catalyzed synthesis of enaminones
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The Grubbs first-generation catalyst has been found to be an effective catalyst for the synthesis of enaminones by coupling thioamides with α-diazodicarbonyl compounds. The reaction is successful in converting primary, secondary, and tertiary thioamides into their corresponding enaminones. The reaction is also suitable for the synthesis of chiral enaminones.
- Koduri, Naga Durgarao,Scott, Halee,Hileman, Bethany,Cox, Justin D.,Coffin, Michael,Glicksberg, Lindsay,Hussaini, Syed R.
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supporting information; experimental part
p. 440 - 443
(2012/03/10)
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- Thionations using a P4S10-pyridine complex in solvents such as acetonitrile and dimethyl sulfone
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Tetraphosphorus decasulfide (P4S10) in pyridine has been used as a thionating agent for a long period of time. The moisture-sensitive reagent has now been isolated in crystalline form, and the detailed structure has been determined by X-ray crystallography. The thionating power of this storable reagent has been studied and transferred to solvents such as acetonitrile in which it has proven to be synthetically useful and exceptionally selective. Its properties have been compared with the so-called Lawesson reagent (LR). Particularly interesting are the results from thionations at relatively high temperatures (165 °C) in dimethyl sulfone as solvent. Under these conditions, for instance, acridone and 3-acetylindole could quickly be transformed to the corresponding thionated derivatives. Glycylglycine similarly gave piperazinedithione. At these temperatures, LR is inefficient due to rapid decomposition. The thionated products are generally cleaner and more easy to obtain because in the crystalline reagent, impurities which invariably are present in the conventional reagents, P4S 10 in pyridine or LR, have been removed. 2011 American Chemical Society.
- Bergman, Jan,Pettersson, Birgitta,Hasimbegovic, Vedran,Svensson, Per H.
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experimental part
p. 1546 - 1553
(2011/06/11)
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- Studies on the Eschenmoser coupling reaction and insights on its mechanism. Application in the synthesis of Norallosedamine and other alkaloids
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The conditions of the Eschenmoser coupling reaction were studied. The formation of the α-thioiminium ion was achieved faster in the presence of an additive (NaI) and dry chloroform as the preferred solvent. The developed conditions were used for the second part of the reaction (the sulfur extrusion itself). The present protocol avoids the formation of byproducts, which were previously described as a major drawback to be overcome. Electrospray ionization tandem mass spectrometry was used to characterize some aspects (intermediates) of the first step of the reaction mechanism. Some reduction conditions were properly tested and the selected conditions were applied to the synthesis of the natural alkaloid Norallosedamine and other derivatives.
- Neto, Brenno A.D.,Lapis, Alexandre A.M.,Bernd, Alinne B.,Russowsky, Dennis
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experimental part
p. 2484 - 2496
(2009/08/07)
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- Synthesis of ω-aminodithioesters
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ω-Aminodithioester derivatives were obtained from thionolactams by reaction with an alkyl triflate followed by thiolysis with hydrogen sulfide. The presence of an electron-withdrawing group was required on the N1 position (p-nitrophenyl or benzoyl) to favor the ring opening of γ-, δ- and ε-thionolactams. In the case of β-thionolactam, activation was provided by a CF2 motif in C3 position. Georg Thieme Verlag Stuttgart.
- Lacroix, Simon,Rixhon, Vinciane,Marchand-Brynaert, Jacqueline
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p. 2327 - 2334
(2008/02/03)
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- Silver-catalyzed hydroamination: Synthesis of N-bridgehead pyrroles, incorporating a protection-deprotection strategy for preparation of cyclic secondary vinylogous carbamates
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N-Bridgehead pyrroles are efficiently prepared from cyclic secondary vinylogous carbamates using a two-step sequence. This sequence involves C-propargylation followed by a silver-catalyzed intramolecular hydroamination. Hydroamination is brought about using microwave irradiation and affords the desired N-bridgehead pyrroles rapidly and in good yield. Cyclic secondary vinylogous carbamates are prepared using a mild, economical procedure. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
- Robinson, Ross S.,Dovey, Martin C.,Gravestock, David
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p. 505 - 511
(2007/10/03)
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- An efficient synthesis of chiral cyclic β-amino acids via asymmetric hydrogenation
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Cyclic β-amino acids, homoproline, homopipecolic acid and 3-carboxy-methylmorpholine were obtained in high enantiomeric excesses by transition metal-catalyzed asymmetric hydrogenation of cyclic β-acylamino-alkenoates. These compounds were synthesized by a
- Pousset, Cyrille,Callens, Roland,Marinetti, Angela,Larchevêque, Marc
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p. 2766 - 2770
(2007/10/03)
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- Substituted 2-iminopiperidines as inhibitors of human nitric oxide synthase isoforms
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A series of analogues of 2-iminopiperidine have been prepared and shown to be potent inhibitors of the human nitric oxide synthase (NOS) isoforms. Methyl substitutions on the 4-position (3) or 4- and 6-positions (8) afforded the most potent analogues. These compounds exhibited IC50 values of 0.1 and 0.08 μM, respectively, for hiNOS inhibition. Substitution with cyclohexylmethyl at the 6-position (13) afforded an inhibitor that showed the best selectivity for hiNOS versus heNOS (heNOS IC50/hiNOS IC50 = 64). Following oral administration, inhibitors were found to decrease serum nitrite/nitrate levels in an in vivo rat endotoxin assay. This series of 2- iminopiperidines were prepared via the described synthetic methodologies. The effect of ring substitutions on potency and selectivity for this class of cyclic amidines as NOS inhibitors is described.
- Webber, R. Keith,Metz, Suzanne,Moore, William M.,Connor, Jane R.,Currie, Mark G.,Fok, Kam F.,Hagen, Timothy J.,Hansen Jr., Donald W.,Jerome, Gina M.,Manning, Pamela T.,Pitzele, Barnett S.,Toth, Mihaly V.,Trivedi, Mahima,Zupec, Mark E.,Siong Tjoeng
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- A study of vinyl radical cyclization onto the azido group by addition of sulfanyl, stannyl, and silyl radicals to alkynyl azides
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Thermal radical reactions of azidoalkynes 2, 8, 14, and 21a-c with thiols 1a-c afford 2-sulfanylvinyl radicals by selective addition of sulfanyl radicals to the triple bond. 1-Phenylvinyl radicals 23 and 30a, as well as vinyl radical 30b, undergo fast 5-cyclization onto the aromatic azide function to give cyclized indoles. In contrast, both 1-phenyl (15, 17) and 1-alkyl (3a,b, 9) vinyl radicals fail to add to their aliphatic azido substituents and exclusively undergo cyclization onto the aromatic sulfanyl ring and H transfer from the thiol precursor. Azidoalkynes 14 and 21a react with Bu3SnH and TMSS under radical conditions to give instead the corresponding amines as a result of preferential attack of Bu3Sn · and (TMS)3Si · radicals on the azido group rather than on the triple bond. Evidence is provided that alkyl radical cyclizations onto azides are not feasible in the presence of thiol, in contrast with the reported utility of these cyclization reactions in the presence of Bu3SnH and TMSS.
- Montevecchi, Pier Carlo,Navacchia, Maria Luisa,Spagnolo, Piero
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p. 1219 - 1226
(2007/10/03)
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- Reaction of lactim ethers and lactim sulfides with electrophiles: Attack at nitrogen followed by ring-opening under neutral conditions
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Electrophilic push-pull molecules react at the nitrogen of lactim ethers and lactim sulfides; subsequent hydrolysis gives ring-opened products in good yields.
- Anbazhagan, Mariappan,Dixit, Arun N.,Rajappa, Srinivasachari
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p. 2421 - 2424
(2007/10/03)
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- 8H-ANHYDRO-4-HYDROXY-2-OXO-1,3-THIAZINUM HYDROXIDES AS MESOIONIC 1,4-DIPOLES
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The previously unknown 8H-anhydro-4-hydroxy-2-oxo-1,3-thiazinum hydroxides (1) were prepared and their 1,4-dipolar cycloaddition behavior was examined.In most cases, elimination of the proton in the 8-position of the mesoionic ring was observed to occur unless extremely reactive dipolarophiles were used.The S,N-ketene acetals were converted to the corresponding α-diazo ketones for further study.
- Padwa, Albert,Coats, Steven J.,Hadjiarapoglou, Lazaros
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p. 1631 - 1652
(2007/10/03)
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- 8H-Anhydro-4-hydroxy-2-oxo-1,3-thiazinium Hydroxides as mesoionic 1,4-Dipoles
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The previously unknown 8H-anhydro-4-hydroxy-2-oxo-1,3-thiazinium hydroxides (1) were prepared and their 1,4-dipolar cycloaddition behavior was examined.In most cases, elimination of the proton in the 8-position of the mesoionic ring was observed to occur unless extremely reactive dipolarophiles were used.The S,N-ketene acetals were converted to the corresponding α-diazo ketones for further study.
- Padwa, Albert,Coats, Steven J.,Hadjiarapoglou, Lazaros
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p. 219 - 242
(2007/10/02)
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- Transformation of Alkyl N-(Vinyloxy)benzimidates to Alkyloxazoles. Mechanism and Extension
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Transformation of alkyl N-(vinyloxy)benzimidates to alkyloxazoles proceeds through the intermediates: a charge-separated 1,2-oxazetidine derivative and then 1-hydroxy-2-imino>maleic acid diester, while their photochemical transformation takes place via a concerted sigmatropic shift.As the extension of this reaction, the preparation of the precursor proposed for virginiamycin M2 synthesis and the reaction of N-analogs of alkyl N-(vinyloxy)benzimidates are described.
- Yokoyama, Masataka,Menjo, Yasuhiro,Ubukata, Makoto,Irie, Masakazu,Watanabe, Mikari,Togo, Hideo
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p. 2219 - 2226
(2007/10/02)
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- Effects of structural changes on acidities and homolytic bond dissociation energies of the N-H bonds in pyridones and related heterocycles
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Equilibrium acidities in DMSO have been obtained for the H-N (or H-O) bonds in 2-, 3-, and 4-aminopyridines, 3-hydroxypyridine, 2- and 4-pyridones, 2-piperidone, and 2-quinolone, as well as thio analogues in which the C=O bond has been replaced by C=S. Homolytic bond dissociation energies (BDEs) for the acidic H-A bonds in these molecules have been estimated by combining the pKHA values with the oxidation potentials of their conjugate bases, Eox(A-). The acidity order for the aminopyridines was found to be 4 > 2 > 3 whereas the BDEs of their N-H bonds decreased in the opposite order, 3 > 2 > 4. The N-H bond of 2-pyridone was found to be 9.4 pKHA units (12.9 kcal/mol) more acidic than its saturated analogue, 2-piperidone, whereas its homolytic bond dissociation energy was found to be about 12 kcal/mol weaker. The 2- and 4-pyridones and 2-quinolone exhibit homo-hydrogen bonding whereas their thio analogues do not. The stabilization energy of the 2-thiopyridonyl radical was estimated to be 17 kcal/mol greater than that of the 2-pyridonyl radical, which explains the much greater ease with which esters of N-hydroxy-2-thiopyridone compared to esters of N-hydroxy-2-pyridone produce radicals in the Barton reaction.
- Bordwell,Singer, Debra L.,Satish
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p. 3543 - 3547
(2007/10/02)
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- Diethylborylierung und Sulfidierung von ω-Lactamen
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Several reaction modes of ω-lactams with Et3B are observed between 20 and 110 deg C.The Et2B lactims (1) having various degrees of association x; 1b; (1d)2 (X-ray structure); 1e; (1f)4> are formed by elimination of 1 mol of ethane.The condensation products result by elimination of 1.33 mol of ethane together with the lactim derivatives (3b; 3c).Thermolysis (>125 deg C) of (1d)2, 1e, and (1f)4 leads to mixtures, in which the compounds 2d, e,f and 3d, e, f, resp., have been identified (NMR, MS).Differences of the thermal behaviour of 1a-f (s-cis/trans conformers, cis/trans lactims, association degree) are discussed. - From 2b,c and Hacac the N-acylamidines (4b,c) are obtained, which react with (9-BBN)2S to yield the monomeric 9-BBN-ω-thiolactims .The latter react with MeOH to give the ω-thiolactams (6b,c) and 9-MeO-9-BBN, from which the 2:2 MeOH addition compound (7)2 (X-ray structure) is obtained. Key Words: ω-Lactimes, boryl derivatives of/ω-Lactimes, condensation of/Amidines, N-acyl, borylsulfoboration of/ω-Tholactims, 9-BBN derivatives of/ω-Thiolactimes.
- Koester, Roland,Kucznierz, Ralf,Schuessler, Wilhelm,Blaeser, Dieter,Boese, Roland
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p. 189 - 200
(2007/10/02)
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- Photochemical δ-Hydrogen Abstraction from Acyclic and Semicyclic Monothioimides
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Photochemical δ-hydrogen abstraction from acyclic and semicyclic monothioimides have been studied.Photolysis of acyclic monothioimides possessing a benzylic hydrogen atom at the δ-position gave γ-lactams, via a 1,5-diradical intermediate, accompanied by thioamides were generated by γ-hydrogen abstraction.Irradiation of the five-membered semicyclic monothioimide, N-(3-phenylpropionyl)pyrrolidine-2-thione, yielded 5-mercapto-4-phenyl-1-azabicyclooctan-2-one.For N-(3-phenylbutyryl)pyrrolidine-2-thione, disproportionation, involving 1,6-hydrogen migration, was the main path.Photolysis of the six-membered semicyclic monothioimide, N-(3-phenylbutyryl)piperidine-2-thione, gave an unsaturated thiol, via a 1,4-hydrogen shift of a 1,5-diradical intermediate, accompanied by cyclisation product and piperidine-2-thione.
- Sakamoto, Masami,Tohnishi, Masakazu,Fujita, Tsutomu,Watanabe, Shoji
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p. 347 - 351
(2007/10/02)
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- In Situ Reagent for Thionation of Amides, Peptides and Lactams
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An in situ reagent 1A for thionation of amides, peptides and lactams is prepared from phosphorus decasulfide/sodium carbonate (1:1 ratio) in THF at 25 deg C.
- Brillon, Denis
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p. 3085 - 3095
(2007/10/02)
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- Reaction of Phosphorus Pentasulfide with Organolithiums. An In Situ Reagent for the Preparation of Thiolactams
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Phosphorus pentasulfide reacts under mild conditions with four equivalents of n-butyllithium, methyllithium or phenyllithium giving solutions in tetrahydrofuran.The new reagents in situ convert lactams to thiolactams and show significant selectivity in the type of reactive lactams.
- Goel, O. P.,Krolls, U.
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p. 162 - 164
(2007/10/02)
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- Platinum chelates of 2-hydrazino-azoles
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This disclosure describes platinum chelates of 2-hydrazino-1-aza (or 1,3-diaza,1-oxa-3-aza or 1-thia-3-aza)-1-cyclo-alkenes which possess activity as antitumor agents.
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