- Vilsmeier Formylation of O-Silylated Enolates of Carboxylic Esters. A New Method for the Synthesis of α-Formylcarboxylic Esters
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The Vilsmeier formylation of ketene O-alkyl O'-silyl acetals (O-silylated enolates of carboxylic esters) provides α-formylcarboxylic esters in moderate yields.
- Reddy, Chaganti P.,Tanimoto, Shigeo
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- A facile and convenient synthesis of (±)-biotin via MgCl2/Et3N-mediated C-C coupling and Mitsunobu reaction
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A synthesis of (±)-biotin is described starting from simple starting materials viz. cyclohexanone and amino malonic acid ester. The key steps involved are MgCl2/Et3N coupling of amino malonic acid ester derivative and acid chloride,
- Chavan, Subhash P.,Chavan, Prakash N.,Lasonkar, Pradeep B.,Khairnar, Lalit B.,Kadam, Appasaheb L.
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- β-Chloroaldehydes from Trapping Zirconium Enolates Produced in Asymmetric 1,4-Additions
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Zirconium enolates, derived from copper-catalyzed asymmetric conjugate additions, are trapped with the Vilsmeier-Haack reagent. Asymmetric additions generate quaternary carbon centers with high enantioselectivity (generally ?90% ee), and the enolates are converted to unsaturated β-chloroaldehydes (41-57% yields). The reaction tolerates changes to the nucleophile, can be used to form five-, six-, or seven-membered ring products, and is scalable to 5 mmol, and the products are readily elaborated by condensation, cross coupling, and addition reactions.
- Wang, Jiao Yu Joseph,Palacin, Thomas,Fletcher, Stephen P.
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- A General Strategy for Macrotheranostic Prodrug Activation: Synergy between the Acidic Tumor Microenvironment and Bioorthogonal Chemistry
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Prodrugs activated by endogenous stimuli face the problem of tumor heterogeneity. Bioorthogonal prodrug activation that utilizes an exogenous click reaction has the potential to solve this problem, but most of the strategies currently used rely on the pre
- Dong, Yansong,Tu, Yalan,Wang, Jun,Wang, Kewei,Xu, Congfei,Yuan, Youyong
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supporting information
p. 7168 - 7172
(2020/03/23)
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- Cyclization of β-Chlorovinyl Thiohydrazones into Pyridazines: A Mechanistic Study
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Extensive experimental and theoretical investigations on the isomerization and heterocyclizations of β-chlorovinyl thiohydrazones derived from oxamic acid thiohydrazides and β-chlorovinyl aldehydes were performed to elucidate the reaction mechanism of pyr
- Komendantova, Anna S.,Fakhrutdinov, Artem N.,Menchikov, Leonid G.,Sukhorukov, Alexey Yu.,Zavarzin, Igor V.,Volkova, Yulia A.
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supporting information
p. 527 - 536
(2018/10/31)
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- Two-Step Synthesis of 3,4-Dihydropyrrolopyrazinones from Ketones and Piperazin-2-ones
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An expedient two-step synthesis of 3,4-dihydropyrrolopyrazinones has been achieved via a Vilsmeier-Haack reaction of ketones, followed by an annulation of the corresponding chloroaldehydes with commercially available piperazin-2-ones. A variety of cyclic and acyclic ketones and piperazin-2-ones participated in this two-step chemistry, affording the desired 3,4-dihydropyrrolopyrazinones in up to 78% yield.
- Sandoval, Cosme,Lim, Ngiap-Kie,Zhang, Haiming
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p. 1252 - 1255
(2018/02/22)
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- Efficient synthesis of 4- And 5-substituted 2-aminopyrimidines by coupling of β-Chlorovinyl Aldehydes and Guanidines
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A general, practical, and simple synthesis of functionalized 2-aminopyrimidines starting from β-chlorovinyl aldehydes and amidines is reported. In the presence of potassium carbonate, various ketones have been efficiently transformed into the pyrimidine derivatives by a two-step sequence involving the Vilsmeier-Haack reaction followed by a condensation reaction with guanidines. The protocol is distinguished by operational simplicity, inexpensive reagents, and functional-group tolerance. In many cases, pure solid products can be obtained in high to excellent yields without using column chromatography. The synthetic value of the method was demonstrated by the efficient synthesis of steroidal pyrimidines and a precursor of the antitumor agents Imatinib and Mocetinostat.
- Komendantova, Anna S.,Komkov, Alexander V.,Volkova, Yulia A.,Zavarzin, Igor V.
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supporting information
p. 4247 - 4254
(2018/08/24)
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- Synthesis, structure and reactivity of β-chalcocyclohexenals: Dichalcogenides and chalcogenides
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The present work describes the synthesis and characterization of a series of organochalcogen compounds derived from β-chlorocyclohexenal (27a)/β-bromocyclohexenal (27b) which are stabilized by E...O (E = S, Se, Te) intramolecular secondary bonding interaction (IM-SBI). Di-(2-formylcyclohex-1-ene)sulfide (21) was prepared by treating 27b with disodium sulfide. Di-(2-formylcyclohex-1-ene)diselenide (28) was obtained by reacting 27a with disodium diselenide. The reaction always produced a mixture of di-(2-formylcyclohex-1-ene)diselenide (28) and di-(2-formylcyclohex-1-ene)selenide (29). Attempts to synthesize di-(2-formylcyclohex-1-ene)ditelluride 30 by the reaction of 27b with disodium ditelluride afforded a mixture of monotellurides; 3,4,5,6,7,8-hexahydro-2H-9-telluraanthracene-1-carbaldehyde (26), di-(2-formylcyclohex-1-ene)telluride (22) and 9-hydroxy-2,3,5,6,7,8,9,9a-octahydro-1H-telluroxanthene-4-carbaldehyde (31). Reactions of 28 with halogenating reagents afforded the corresponding organylselenenyl halides; selenenyl chloride 35, selenenyl bromide 36 and selenenyl iodide 37. Tellurides 26 and 22 were used as ligands for metal complexation reactions.
- Prasad, Poonam R.,Singh, Harkesh B.,Butcher, Ray J.
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- COMPOUNDS AND METHODS OF TREATING OCULAR DISORDERS
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A method of treating an ocular disorder in a subject associated with increased all-trans-retinal in an ocular tissue includes administering to the subject a therapeutically effective amount of a primary amine compound of formula (I); and pharmaceutically acceptable salts thereof.
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Paragraph 00198
(2016/06/14)
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- Expansion of first-in-class drug candidates that sequester toxic all-trans-retinal and prevent light-induced retinal degeneration
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All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation.
- Zhang, Jianye,Dong, Zhiqian,Mundla, Sreenivasa Reddy,Hu, X. Eric,Seibel, William,Papoian, Ruben,Palczewski, Krzysztof,Golczak, Marcin
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supporting information
p. 477 - 491
(2015/01/30)
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- Highly regio- And enantioselective synthesis of g,d-unsaturated amido esters by catalytic hydrogenation of conjugated enamides
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An efficient and highly regio- and enantioselective catalytic asymmetric hydrogenation of a,γ-dienamido esters to g,d-unsaturated amido esters has been achieved using Rh/ TangPhos as the catalyst. A series of γ,δ-unsaturated amido acids were furnished in excellent yields with up to 99%ee. This effective methodology was applied in the asymmetric synthesis of key intermediate of Ramipril, an ACE inhibitor.
- Min, Gao,Jing-jing, Meng,Hui, Lv,Xumu, Zhang
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supporting information
p. 1885 - 1887
(2015/02/19)
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- A Straightforward Approach toward Multifunctionalized Pyridazines via Imination/Electrocyclization
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A facile synthesis of functionalized 3-carbamide pyridazines starting from readily available chlorovinyl aldehydes and oxamic acid thiohydrazides via cascade imination/electrocyclization is reported. In the presence of p-toluenesulfuric acid, various ketones have been efficiently incorporated into the pyridazine derivatives through a two-step sequence involving a Vilsmeier-Haack reaction and imination. The synthetic value of this method has been demonstrated by efficient synthesis of steroidal pyridazines.
- Komkov, Alexander V.,Komendantova, Anna S.,Menchikov, Leonid G.,Chernoburova, Elena I.,Volkova, Yulia A.,Zavarzin, Igor V.
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supporting information
p. 3734 - 3737
(2015/08/18)
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- Synthesis of substituted azulenes via Pt(II)-Catalyzed ring-expanding cycloisomerization
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Substituted azulenes, valuable structures for electronic devices and pharmaceuticals, have been synthesized by the platinum(II)-catalyzed intramolecular ring-expanding cycloisomerization of 1-en-3-yne with ortho-disubstituted benzene. This novel method provides an alternative route for the efficient synthesis of substituted azulenes. The reaction mechanism of selected catalytic transformations was explored using density functional calculations.
- Usui, Kazuteru,Tanoue, Kensuke,Yamamoto, Kosuke,Shimizu, Takashi,Suemune, Hiroshi
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supporting information
p. 4662 - 4665
(2015/01/16)
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- A photo-induced C-O bond formation methodology to construct tetrahydroxanthones
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A metal-free, photo-induced C-O bond formation methodology was developed to construct tetrahydroxanthones. This mild and efficient methodology was based on intramolecular oxygen trapping of the reactive species produced by photolytic activation of a C-Cl
- Xiao, Zheming,Cai, Shujun,Shi, Yingbo,Yang, Baochao,Gao, Shuanhu
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supporting information
p. 5254 - 5257
(2014/05/06)
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- Fragmentation of bicyclic γ-silyloxy-β-hydroxy-α- diazolactones as an approach to ynolides
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Medium-sized ynolides were prepared by the Lewis acid-mediated fragmentation of bicyclic γ-silyloxy-β-hydroxy-α-diazolactones in which the Cβ-Cγ bond is the ring fusion bond. Although these lactone fragmentation substrates reacted somewhat less efficientl
- Bayir, Ali,Brewer, Matthias
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p. 6037 - 6046
(2014/07/21)
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- PYRROLOPYRIDINONE COMPOUNDS AND METHODS FOR TREATING HIV
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Provided are compounds and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and their use for treating viral infections mediated by a member of the retrovirus family of viruses such as the Human I
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Page/Page column 115
(2013/04/10)
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- A novel and enantioselective synthesis of d-(+)-biotin via a Sharpless asymmetric dihydroxylation strategy
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A novel and enantioselective synthesis of d-(+)-biotin has been accomplished starting from commercially available cyclohexanone. The key steps in the sequence are the Sharpless asymmetric dihydroxylation of a (E)-ethyl 3-(2-chlorocyclohex-1-en-1-yl)acryla
- Chavan, Subhash P.,Lasonkar, Pradeep B.,Chavan, Prakash N.
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p. 1473 - 1479
(2013/12/04)
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- Palladium(II) 3-iminophosphine (3IP) complexes: Active precatalysts for the intermolecular hydroamination of 1,2-dienes (allenes) and 1,3-dienes with aliphatic amines under mild conditions
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The synthesis of alicyclic 3-iminophosphine ligands is extended to include a new framework incorporating a cyclohexenyl backbone with an N-aryl imino functionality (3IPAr). Accordingly, a series of palladium(II) complexes employing this new lig
- Kuchenbeiser, Glenn,Shaffer, Andrew R.,Zingales, Nicholas C.,Beck, John F.,Schmidt, Joseph A.R.
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experimental part
p. 179 - 187
(2011/02/17)
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- A general and efficient approach to 2H-indazoles and 1H-pyrazoles through copper-catalyzed intramolecular N-N bond formation under mild conditions
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A new efficient copper-catalyzed intramolecular amination reaction has been developed to readily synthesise a wide variety of multi-substituted 2H-indazole and 1H-pyrazole derivatives from easily accessible starting materials under mild conditions. A highly selective ligand for estrogen receptor β was prepared in three steps by employing this method. The Royal Society of Chemistry 2011.
- Hu, Jiantao,Cheng, Yongfeng,Yang, Yiqing,Rao, Yu
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supporting information; experimental part
p. 10133 - 10135
(2011/10/09)
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- Intramolecular Fe(II)-Catalyzed N-O or N-N bond formation from aryl azides
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(Figure presented) Iron(II) bromide catalyzes the transformation of aryl and vinyl azides with ketone or methyl oxime substituents into 2,1-benzisoxazoles, indazoles, or pyrazoles through the formation of an N-O or N-N bond. This transformation tolerates a variety of different functional groups to facilitate access to a range of benzisoxazoles or indazoles. The unreactivity of the Z-methyloxime indicates that N-heterocycle formation occurs through a nucleophilic attack of the ketone or oxime onto an activated planar iron azide complex.
- Stokes, Benjamin J.,Vogel, Carl V.,Urnezis, Linda K.,Pan, Minjie,Driver, Tom G.
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supporting information; experimental part
p. 2884 - 2887
(2010/08/21)
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- Efficient synthesis of a new type of baylis-hillman adducts and their stereoselective bromination
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A new type of Baylis-Hillman adducts derived from chlorovinyl aldehydes were prepared via Vilsmeier reaction of ketones with a bis(trichloromethyl) carbonate (BTC)/DMF system to construct chlorovinyl aldehydes, followed by sonochemical Baylis-Hillman reaction under solvent-free conditions. The stereoselective bromination of these new compounds with a Br2-Ph3P system has been achieved efficiently with good to excellent yields under mild conditions. Copyright Taylor & Francis Group, LLC.
- Zhong, Weihui,Jiang, Lingbo,Guo, Baoming,Wu, Yaotiao,Hong, Lingjuan,Chen, Yanhui
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experimental part
p. 2441 - 2456
(2010/09/05)
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- Synthesis of a novel series of thieno[3,2-d]pyrimidin-4-(3H)-ones
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2-Aminothieno[3,2-d]pyrimidin-4-ones were synthesized in one step by condensation of 3-amino(benzo)thiophene car-boxylate with chloroformamidine hydrochloride. Georg Thieme Verlag Stuttgart.
- Abdillahi, Ismail,Kirsch, Gilbert
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scheme or table
p. 1428 - 1430
(2010/10/03)
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- POLYCYCLIC ANTAGONISTS OF LYSOPHOSPHATIDIC ACID RECEPTORS
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Described herein are compounds that are antagonists of lysophosphatidic receptor(s). Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such antagonists, alone and in combination with other compounds, for treating LPA-dependent or LPA-mediated conditions or diseases.
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(2010/12/29)
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- Synthesis, cytotoxicity and effects of some 1,2,4-triazole and 1,3,4-thiadiazole derivatives on immunocompetent cells
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Novel derivatives of 4,5-substituted-1,2,4-triazole-thiones and 2,5-substituted-1,3,4-thiadiazoles were synthesized and evaluated for their cytotoxicity. The biological study indicated that compounds 4-ethyl-5-(4,5,6,7-tetrahydro-1-benzothien-2-yl)-2,4-di
- Mavrova, Anelia Ts.,Wesselinova, Diana,Tsenov, Yordan A.,Denkova, Pavletta
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experimental part
p. 63 - 69
(2009/04/07)
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- Titanacyclobutenes or titanium vinyl carbene complexes? Reactivity of organotitanium species generated by the reaction of γ-chloroallyl sulfides with a titanocene(II) reagent
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The reactivity of the organotitanium species generated by the reductive titanation of γ-chloroallyl sulfides with the titanocene(II) reagent [Cp2Ti{P(OEt)3}2] was studied. The organotitanium species formed from α-monosubstituted γ-chloroallyl sulfides reacted with 1,5-diphenylpentan-3-one and styrene to produce conjugated dienes and vinyl cyclopropanes as major products, thus suggesting the formation of vinyl carbene complexes as intermediates. On the contrary, the organotitanium species generated from acyclic β,γ-disubstituted γ-chloroallyl sulfides revealed titanacyclobutene-like reactivity, and their reaction with 1,5-diphenylpentan-3-one produced homoallyl alcohols. These organotitanium species did not react with styrene, but did react with dichlorophenylphosphine to afford phosphacyclobutenes. In the case of β-monosubstituted, γ-monosubstituted, and α,γ- disubstituted γ-chloroallyl sulfides, the organotitanium species reacted with both 1,5-diphenylpentan-3-one and styrene. The former reaction produced homoallyl alcohols and the latter gave vinyl cyclopropanes or unconjugated dienes. These results suggest that titanacyclobutenes and/or titanium vinyl carbene complexes are produced by the reductive titanation of γ-chloroallyl sulfides depending on their substitution patterns.
- Shono, Tomohiro,Kurashige, Rie,Mukaiyama, Ryo,Tsubouchi, Akira,Takeda, Takeshi
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p. 4074 - 4080
(2008/02/08)
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- Synthesis and evaluation of isoxazole derivatives as lysophosphatidic acid (LPA) antagonists
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A series of isoxazole derivatives were synthesized and their antagonistic activities against LPA stimulation on both LPA1/CHO cells and rHSC cells were evaluated. Among them, 3-(4-{4-[1-(2-chloro-cyclopent-1-enyl)-ethoxycarbonylamino]-isoxazol-3- yl}-benzylsulfanyl)-propionic acid (34) showed the most potent activities.
- Yamamoto, Takashi,Fujita, Koichi,Asari, Sayaka,Chiba, Akira,Kataba, Yuka,Ohsumi, Koji,Ohmuta, Naoko,Iida, Yuko,Ijichi, Chiori,Iwayama, Satoshi,Fukuchi, Naoyuki,Shoji, Masataka
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p. 3736 - 3740
(2008/02/07)
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- Novel azole compound
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Azole compounds represented by formula I: wherein ring A is isoxazole and the like, R1 is a substituted or unsubstituted aryl group and the like, R2 is a hydrogen atom and the like, and R3 is a substituted or unsubstituted alkyl group and the like, and pharmaceutically acceptable salts thereof inhibit the physiological activity of lysophosphatidic acid (LPA), and are useful as for the prophylaxis or treatment of diseases in which inhibition of the physiological activity of LPA is useful for the prophylaxis or treatment thereof, such as diseases involving the LPA receptor.
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Page/Page column 33
(2008/06/13)
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- Chemoselective electrophilic oxidation of heteroatoms by hydroperoxy sultamst
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The synthesis of novel hydroperoxy sultams 1b-d and their potential as renewable chemoselective electrophilic oxidants for a wide range of nitrogen, sulfur, and phosphorus heteroatoms in nonaqueous media is described. Reactions of 1b,c with secondary amines 10f,g yielded the hydroxysultams 2b,c and nitrone 11f or radical 11g depending on the substrate and stoichiometry, while tertiary amines 10a-d gave amine oxides 11a-d. Compounds 1c,d oxidized various thioethers 12a-g to sulfoxides 13a-g smoothly that were isolated by chromatography in nearly quantitative yields. 1c was regenerated from 2c by treatment of the latter with acidified H2O2. Kinetic studies of the reaction of 1c with 1,4-thioxane 12f suggest that the reaction follows the second-order kinetics, first order in substrate and first order in oxidant with the second-order rate constant several orders of magnitude larger than that of the corresponding reaction with hydrogen peroxide and tert-butyl hydroperoxide without the need for any acid or heavy metal catalysts. The phosphines 14a,b were also oxidized by 1c to the respective phosphine oxides 15a,b readily in quantitative yields. The reactions may be conducted at ambient temperature or lower and appear to proceed via a nonradical mechanism. Reactions are sensitive to steric as well as electronic factors.
- Gelalcha, Feyissa Gadissa,Schulze, Baerbel
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p. 8400 - 8406
(2007/10/03)
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- Highly Regio- and Diastereoselective One-Pot Synthesis of Silyl Epoxy Alcohols and Vinylsilanes by Direct Hydroxy-Epoxidation
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A direct synthesis of silyl epoxy alcohols from vinylsilanes is described.It consists of the regioselective ene reaction of the vinylsilanes with singlet oxygen, which proceeds with predominant hydrogen abstraction at the position geminal to the silyl group.The resulting silyl allylic hydroperoxides were treated, without isolation, subsequently with Ti(O-i-Pr)4 to afford the silyl epoxy alcohols in good yields and very high diastereomeric ratios, which ranged from 93:7 to greater than 97:3.Alternatively, the vinylsilanes were photooxygenated directly in the presence of the titanium catalyst and the silyl epoxy alcohols obtained in good yields.The method was applied to di- and trisubstituted acyclic vinylsilanes with a methyl group geminal to silicon and cyclic derivatives all give consistently good results.In this novel hydroxy-epoxidation, the regioselectivity of the singlet oxygen ene reaction as well as the diastereoselectivity of the oxygen transfer can be controlled by the steering effects of the silyl group.
- Adam, Waldemar,Richter, Markus J.
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p. 3341 - 3346
(2007/10/02)
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- (2-CHLOROVINYL)CHLOROCARBENES: GENERATION AND REACTIONS WITH ALKENES
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The treatment of Z-1,1,3-trichloro-4,4-dimethyl-2-pentene (Ia) with t-C4H9OK in boiling hexane or benzene gave rise to (Z-2-chloro-3,3-dimethyl-1-butenyl)chlorocarbene (IVa), which reacted with alkenes to give the cyclopropane derivatives (V) in 44-57perc
- Shavrin, K.N.,Okonnishnikova, G.P.,Nefedov, O.M.
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p. 2228 - 2234
(2007/10/02)
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