- Design, synthesis and SAR of antitubercular benzylpiperazine ureas
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Abstract: N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of the furan ring in the GSK Tres Cantos molecules with a phenyl ring led to molecule (I) with an MIC of 1?μM against Mtb H37Rv, low cellular toxicity (HepG2 IC50 ~ 80?μM), good DMPK properties and specificity for Mtb. With the aim of delineating the SAR associated with (I), fifty-five analogs were synthesized and screened against Mtb. The SAR suggests that the piperazine ring, benzyl urea and piperonyl moieties are essential signatures of this series. Active compounds in this series are metabolically stable, have low cellular toxicity and are valuable leads for optimization. Molecular docking suggests these molecules occupy the Q0 site of QcrB like Q203. Graphic Abstract: Bioisosteric replacement of N-furfuryl piperazine-1-carboxamides yielded molecule (I) a novel lead with satisfactory PD, metabolism, and toxicity profiles.[Figure not available: see fulltext.]
- Satish, Sohal,Chitral, Rohan,Kori, Amitkumar,Sharma, Basantkumar,Puttur, Jayashree,Khan, Afreen A.,Desle, Deepali,Raikuvar, Kavita,Korkegian, Aaron,Martis, Elvis A. F.,Iyer, Krishna R.,Coutinho, Evans C.,Parish, Tanya,Nandan, Santosh
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- Method for preparing amine compound by alkali-catalyzed decarboxylation (by machine translation)
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The method is simple and convenient (reaction conditions ;), more stable,atom utilization rate, by-products are only carbon dioxide pollution, and the yield can reach. suitable for industrial production Curtis; and the method, Lossen is suitable for industrial production . The method disclosed by the invention is simple and convenient to operate under the action of a base as, rearrangement, rearrangement reaction of an alkyl, aryl or heterocyclic aromatic carboxylic acid or an ester and hydroxylamine compound, 90%. (by machine translation)
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- Enantioselective Synthesis of cis- A nd trans-Borocyclopropylmethanol: Simple Building Blocks to Access Heterocycle-Substituted Cyclopropylmethanols
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An enantioselective and non-oxidative methodology was developed to obtain enantioenriched cyclopropyl boronates using a diethanolamine-promoted selective decomplexation of dioxaborolane. The non-oxidative decomplexation of the dioxaborolane ligand from the cyclopropylmethoxide species formed in the dioxaborolane-mediated Simmons-Smith cyclopropanation reaction provided the enantio?-enriched CIDA-based (CIDA = N-cyclohexyliminodiacetic acid) boro?-cyclopropane in 92% yield and 95.6:4.4 er. A robustness screen has shown diethanolamine to be compatible with esters, carbamates and N-heterocycles, providing a tool to access enantioenriched cyclopropanes carrying not only base-sensitive but oxidizable functional groups as well. Diethanolamine was found to be compatible with the modified zinco-cyclopropanation reaction of allyl alcohol to remove residual dioxaborolane from the corresponding cis-N-heterocycle cyclopropylmethanol, thereby leading to improved yields.
- Charette, André B.,Navuluri, Chandrasekhar,Siddiqui, Saher H.
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p. 3834 - 3846
(2019/10/11)
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- Base-Mediated Intramolecular Decarboxylative Synthesis of Alkylamines from Alkanoyloxycarbamates
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A general and effective method for the synthesis of alkylamine via intramolecular decarboxylation of alkanoyloxycarbamates is described. The alkanoyloxycarbamates are readily prepared with alkyl carboxylic acids and hydroxylamine. The reaction shows a broad range of substrates (primary and secondary alkyl) with functional tolerance, and the corresponding products were obtained in good yields under mild conditions.
- Li, Peihe,Ma, Nuannuan,Wang, Zheng,Dai, Qipu,Hu, Changwen
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p. 8233 - 8240
(2018/05/31)
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- Direct ortho -Selective C-H Functionalization of Carboxybenzyl-Protected Arylalkylamines via Ir(III)-Catalyzed C-H Activation
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A convenient and practical approach to synthesize ortho-alkynylated arylalkylamines through ortho-selective C-H functionalization has been developed using Cbz-amide as the directing group and Ir(III) as the catalyst. Various substrates were well tolerated, affording the corresponding products in moderate to good yields. Moreover, preliminary mechanistic study revealed the role of the amide as the coordination center to cooperate with the Ir(III) complex during C-H activation. Development of this Cbz-amide-promoted CAr-H functionalization offers a practical approach with potential applications in organic synthesis.
- Li, Guobao,Hu, Jundie,Zeng, Runsheng,Shi, Da-Qing,Zhao, Yingsheng
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supporting information
p. 2454 - 2458
(2018/04/26)
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- A base-mediated self-propagative Lossen rearrangement of hydroxamic acids for the efficient and facile synthesis of aromatic and aliphatic primary amines
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A variety of aromatic and aliphatic hydroxamic acids were converted to the corresponding primary amines via base-mediated rearrangement. This rearrangement could proceed with less than 1 equiv. of K2CO3 in polar solvents under thermal conditions with no external reagents. This rearrangement has several features including no external activating agents needed for promoting the rearrangement, less than one equivalent of a base is sufficient for the reaction, and a clean reaction in which only carbon dioxide is produced as a by-product. A self-propagating mechanism via an isocyanate intermediate is proposed and elementary reaction steps, namely, chain propagation reactions are supported by experiments.
- Ohtsuka, Naoya,Okuno, Moriaki,Hoshino, Yujiro,Honda, Kiyoshi
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p. 9046 - 9054
(2016/10/05)
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- N-Urethane protection of amines and amino acids in an ionic liquid
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An efficient, solvent-free protocol for the N-fluorenylmethoxycarbonylation and N-benzyloxycarbonylation of amines is described. The reaction of aliphatic and aromatic amines with FmocOSu and Cbz-Osu in [Bmim][BF4] at room temperature afforded the corresponding N-urethane derivatives in excellent yields and do not require any further purification. The method has been extended to the N-Fmoc and N-Cbz protection of amino acids. Absence of bases, very short reaction times, high yields, selectivity and ease of product separation are some advantages of this protocol.
- Di Gioia,Gagliardi,Leggio,Leotta,Romio,Liguori
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p. 63407 - 63420
(2015/08/11)
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- Photocatalytic decarboxylative reduction of carboxylic acids and its application in asymmetric synthesis
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The decarboxylative reduction of naturally abundant carboxylic acids such as α-amino acids and α-hydroxy acids has been achieved via visible-light photoredox catalysis. By using an organocatalytic photoredox system, this method offers a mild and rapid entry to a variety of high-value compounds including medicinally relevant scaffolds. Regioselective decarboxylation is achieved when differently substituted dicarboxylic acids are employed. The application of this method to the synthesis of enantioenriched 1-aryl-2,2,2-trifluoroethyl chiral amines starting from natural α-amino acids further testifies to the utility of the developed photocatalytic decarboxylative reduction protocol.
- Cassani, Carlo,Bergonzini, Giulia,Wallentin, Carl-Johan
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supporting information
p. 4228 - 4231
(2014/09/30)
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- Microwave-assisted expeditious synthesis of 5-fluoroalkyl-3-(aryl/alkyl)- oxazolidin-2-ones
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An efficient and convenient protocol for synthesis of 5-fluoroalkyl-3- (aryl/alkyl)-oxazolidin-2-ones is described. The reaction of allyl (aryl/alkyl) carbamates with fluoroalkyl iodide initiated by sodium dithionite in aqueous acetonitrile resulted in adducts that undergoes a cyclization assisted by microwave irradiation to form 5-fluoroalkyl-3-(aryl/alkyl)-oxazolidin-2-ones with high yields. It was also found that the products can be more efficiently formed via an AIBN-initiated one-pot addition-cyclization sequence from benzyl allyl(aryl/alkyl) carbamates and fluoroalkyl iodide.
- Yang, Bo,Shi, Luyan,Wu, Jingjing,Fang, Xiang,Yang, Xueyan,Wu, Fanhong
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supporting information
p. 3331 - 3337
(2013/04/24)
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- The direct reductive amination of electron-deficient amines with aldehydes: The unique reactivity of the Re2O7 catalyst
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An unprecedented direct reductive amination of electron-deficient amines such as Cbz-, Boc-, EtOCO-, Fmoc-, Bz-, ArSO2-, Ar2PO-, etc. protected amines with aldehydes is achieved using the Re2O 7 catalyst and silanes as the hydride source. Excellent regioselective mono-alkylation and chemoselective reductive-amination were observed.
- Das, Braja Gopal,Ghorai, Prasanta
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supporting information; experimental part
p. 8276 - 8278
(2012/09/22)
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- INHIBITION OF BACTERIAL BIOFILMS WITH ARYL CARBAMATES
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Disclosure is provided for carbamate compounds that prevent, remove and/or inhibit the formation of biofilms, compositions including these compounds, devices including these compounds, and methods of using the same.
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Page/Page column 33
(2012/02/01)
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- A facile protocol for N-Cbz protection of amines in PEG-600
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An efficient and eco-friendly protocol for the chemoselective N-benzyloxycarbonylation of amines was described. The reaction of amines with benzyl chloroformate (Cbz-Cl) in the presence of PEG-600 at room temperature afforded the corresponding N-Cbz derivatives in excellent yields. The method is applicable to the N-Cbz protection of aliphatic (acyclic and cyclic) and aromatic amines.
- Zhang, Chun Lin,Zhang, Dong Feng,Zhao, Hong Yi,Lin, Zi Yun,Huang, Hai Hong
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experimental part
p. 789 - 792
(2012/08/08)
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- Amberlyst-15 catalyzed Cbz protection of amines under solvent-free conditions
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Amberlyst-15 can effectively catalyze Cbz protection of aliphatic and aromatic amines within 10-15 min under solvent-free conditions. The catalyst can be used repeatedly without loss of activity, and the reaction requires no workup and gives excellent yields. Taylor & Francis Group, LLC.
- Bora, Pranja P.,Vanlaldinpuia, Khiangte,Rokhum, Lalthazuala,Bez, Ghanashyam
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experimental part
p. 2674 - 2683
(2011/08/22)
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- Bromodimethyl sulfonium bromide mediated rapid and facile protection of amines
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A new clean protocol for protection of aryl and aliphatic amines with t-butoxycarbonyl (t-BOC) and benzyloxycarbonyl (Cbz) catalyzed by simple (bromodimethyl) sulfonium bromide has been developed. Rapid protection of amines in excellent yields in totally solvent-free conditions has been achieved. Copyright
- Shailaja,Manjula,Vittal Rao
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experimental part
p. 2073 - 2080
(2011/07/31)
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- Synthesis of carbamates from amines and dialkyl carbonates: Influence of leaving and entering groups
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A number of carbamates were synthesised through a halogen-free process by reacting amines with symmetrical and unsymmetrical carbonates. The results obtained showed a specific trend of preferred leaving groups (in the dialkyl carbonates) depending on whether a catalyst or a base was used. On the other hand, investigations conducted on the preferred entering groups (amines) for the synthesis of carbamates showed the same trend regardless of whether a catalyst or a base was used. Finally, in accordance with the results obtained, it was possible to synthesise sterically hindered carbamates in high yield by transesterification of methyl carbamate with a sterically hindered alcohol. Georg Thieme Verlag Stuttgart New York.
- Tundo, Pietro,McElroy, C. Robert,Aricò, Fabio
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experimental part
p. 1567 - 1571
(2010/09/05)
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- An excellent method for Cbz-protection of amines
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Cbz-protection of aliphatic and aromatic amines can be accomplished with benzylchloroformate using a catalytic amount of dodecatungstophosphoric acid hydrate (0.05 equiv). The reaction is simple, fast, does not require aqueous work-up and gives excellent yields.
- Vanlaldinpuia, Khiangte,Sema, H. Atoholi,Rokhum, Lalthazuala,Bez, Ghanashyam
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experimental part
p. 228 - 229
(2010/08/20)
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- Scope of the Suzuki-Miyaura aminoethylation reaction using organotrifluoroborates
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(Chemical Equation Presented) Potassium β-aminoethyltrifluoroborates were prepared in good yields via hydroboration of the corresponding enecarbamates using the Snieckus hydroborating reagent. A wide variety of phenethylamines containing a potentially fre
- Molander, Gary A.,Jean-Gerard, Ludivine
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p. 8422 - 8426
(2008/03/11)
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- A mild and efficient chemoselective protection of amines as N-benzyloxycarbonyl derivatives in the presence of La(NO3)3·6H2O under solvent-free conditions
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A facile and versatile method for the chemoselective N-benzyloxycarbonylation of amines has been developed by treatment with benzyloxycarbonyl chloride (Cbz-Cl) in the presence of lanthanum(III) nitrate hexahydrate under solvent-free conditions. The metho
- Chinni Mahesh,Narasimhulu,Srikanth Reddy,Suryakiran,Venkateswarlu
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- Microwave-assisted carbamoylation of amines
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The influence of microwave irradiation on the reaction of various amines with benzyl chloroformate and di-tert-butyl dicarbonate was investigated. Microwave irradiation was successfully applied to the carbamoylation of several nonfunctionalized and functionalized amines, including amino acids and nucleobases, leading to satisfactory to high product conversion within very short reaction times. Copyright Taylor & Francis Group, LLC.
- Azzena, Ugo,Dettori, Giovanna,Pisano, Luisa,Pittalis, Mario
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p. 3623 - 3634
(2008/03/13)
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- Selective N,N-dibenzylation of primary aliphatic amines with dibenzyl carbonate in the presence of phosphonium salts
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In the presence of catalytic amounts of tetraalkylphosphonium salts and under solventless conditions, primary aliphatic amines (RNH2: R = PhCH2, Ph(CH2)2, n-decyl, and 1-naphthylmethyl) are efficiently N-benzylated to the corresponding RN(CH2Ph) 2, using dibenzyl carbonate as the benzylating reagent. Compared to the reaction run without salt, where the competitive formation of the benzyl carbamate is favored, the phosphonium salt promotes high selectivity toward the benzylated amine and an increase of the reaction rate as well. However, in a single case explored for an amino acidic compound, namely 4-(aminomethyl) benzoic acid [4-(NH2CH2)C6H4CO 2H], both N,N-dibenzylation and esterification of the acid group were observed. Analysis of the IR vibrational modes of benzylamine in the presence of tetrabutylphosphonium bromide supports the hypothesis that this enhanced selectivity may be due to an acid-base interaction between the salt and the amine, which increases the steric bulk of the amine and favors attack of the nucleophile on the less hindered alkyl terminus of dibenzyl carbonate.
- Loris, Alessandro,Perosa, Alvise,Selva, Maurizio,Tundo, Pietro
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p. 3953 - 3956
(2007/10/03)
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- Preparation of N-substituted aryl and alkyl carbamates and their inhibitory effect on oat seed germination.
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A series of N-substituted aryl and alkyl carbamates (RNHCOOR'; R: aryl, alkyl; R': aryl, alkyl) was prepared and screened for inhibitory activity toward the germination of oat seeds. The activity of each compound was compared with that of chlorpropham (isopropyl 3-chlorocarbanilate). Some of the synthetic carbamates possessing the N-(phenylthio)methyl group, PhSCH2NHCOOR', showed inhibitory activity close or comparable to that of chlorpropham.
- Alizadeh, Babak Heidary,Sugiyama, Takeyoshi,Oritani, Takayuki,Kuwahara, Shigefumi
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p. 422 - 425
(2007/10/03)
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- Benzyl 4,6-dimethoxy-1,3,5-triazinyl carbonate as N-protecting reagent
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A new active carbonate ester, benzyl 4,6-dimethoxy-1,3,5-triazinyl carbonate (Z-DMT), was prepared, and found to be a useful reagent for the introduction of benzyloxycarbonyl group into amines. Since Z-DMT is neither unstable nor irritating, it is practically useful.
- Hioki, Kazuhito,Fujiwara, Miho,Tani, Shohei,Kunishima, Munetaka
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- Efficient Cs2CO3-promoted solution and solid phase synthesis of carbonates and carbamates in the presence of TBAI
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Novel solution and solid-phase methods for the synthesis of carbonates and carbamates were developed using cesium bases and TBAI via a three-component coupling. Cesium carbonate not only promoted successful carbonylations of alcohols and carbamations of amines, but also suppressed common side reactions traditionally seen using existing protocols. Various alcohols and amines were examined, using a wide array of alkyl halides, and the results demonstrated this methodology was highly chemoselective. In particular, use of either sterically demanding substrates or amino acid derivatives afforded the corresponding products exclusively, offering a wide variety of applications such as novel protecting groups and peptidomimetic syntheses.
- Salvatore, Ralph N,Chu, Feixia,Nagle, Advait S,Kapxhiu, Elona A,Cross, Richard M,Jung, Kyung Woon
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p. 3329 - 3347
(2007/10/03)
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- Studies on development of sufficiently chemoselective N-acylation reagents: N-Acyl-N-(2,3,4,5,6-pentafluorophenyl)methanesulfonamides
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A variety of storable N-acyl-N-(2,3,4,5,6-pentafluorophenyl)methanesulfonamides (4a-e) prepared from N-2,3,4,5,6-pentafluorophenylmethanesulfonamide (3), have been developed after systematic research on the structure-reactivity relationship and were found to serve as N-acylation reagents exhibiting sufficiently good chemoselectivity. (C) 2000 Elsevier Science Ltd.
- Kondo, Kazuhiro,Sekimoto, Erika,Nakao, Junko,Murakami, Yasuoki
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p. 5843 - 5856
(2007/10/03)
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- A practical procedure for the preparation of carbamates from azides
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A practical procedure for the direct conversion of azides to carbamates has been found. High yields are obtained when primary and secondary aliphatic azides, as well as α-azido esters, are treated in THF with Me3P and several chloroformates (ClCOOBn, ClCOOMe, ClCOOEt, ClCOOCH2CCl3, ClCOOCH2CH=CH2).
- Ariza, Xavier,Urpi, Felix,Vilarrasa, Jaume
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p. 7515 - 7517
(2007/10/03)
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- Chemoselective alkoxycarbonylation reagent having trifluoromethylsulfonyl-4-trifluoromethylanilide as a leaving group
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N-Benzyloxy- and N-tert-butoxycarbonyltrifluoromethylsulfonyl-4-trifluoromethylanilides were prepared and were found to be chemoselective and shelf-storable alkoxycarbonylation reagents.
- Yasuhara, Tomohisa,Nagaoka, Yasuo,Tomioka, Kiyoshi
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p. 2233 - 2234
(2007/10/03)
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- Zinc promoted simple and convenient synthesis of carbamates: An easy access for amino group protection
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Synthesis of alkyl, aryl, heterocyclic, carbohydrate and amino acid carbamates is described. The protection of the amino group in the presence of other functionality in amino acids demonstrates the importance of this method.
- Yadav,Reddy, Gondi Sudershan,Reddy, M. Muralidhar,Meshram
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p. 3259 - 3262
(2007/10/03)
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- Multilevel selectivity in the mild and high-yielding chlorosilane- induced cleavage of carbamates to isocyanates
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The silane-induced cleavage of a series of N-p-tolylcarbamates and N- phenethylcarbamates to isocyanates has been investigated as a function of chlorosilane, carbamate substituent, and reaction conditions. Reaction yields were determined from the isolated ureas, which were formed by trapping the corresponding isocyanates with isobutylamine. Under room-temperature conditions, multilevel selectivity in carbamate activation has been demonstrated. This selectivity together with the generality of the methodology enhances the utility of carbamates as synthetic intermediates and protecting groups. To demonstrate the effectiveness of this selectivity, a series of biscarbamates were selectively monoactivated to isocyanates in excellent yields.
- Chong, Pek Y.,Janicki, Slawomir Z.,Petillo, Peter A.
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p. 8515 - 8521
(2007/10/03)
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- Fast Atom Bombardment Mass Spectrometry of Carbobenzyloxy-protected Amono Acids and Peptides
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The positive fast atom bombardment (FAB) mass spectra of 15 N-carbobenzyloxy derivatives of α-amino acids are presented together with those of some synthetic peptides containing other widely employed protecting groups.The data obtained allow a fragmentati
- Danieli, Bruno,Rubino, Federico Maria,Cremonesi, Alfredo
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p. 225 - 229
(2007/10/02)
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- PALLADIUM-CATALYZED TRIETHYLAMMONIUM FORMATE REDUCTION OF ARYL TRIFLATES. A SELECTIVE METHOD FOR THE DEOXYGENATION OF PHENOLS
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Phenols can be selectively deoxygenated by reduction of the corresponding aryl triflates with triethylammonium formate in the presence of a homogeneous palladium catalyst.
- Cacchi, Sandro,Ciattini, Pier Giuseppe,Morera, Enrico,Ortar, Giorgio
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p. 5541 - 5544
(2007/10/02)
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- Pyrolysis of Benzyl 2-Oxazolecarbamates and Benzyl 4-Alkylallophanates
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The pyrolysis of benzyl 2-oxazolecarbamates (I) and benzyl 4-alkylallophanates (II) was investigated.Heating of benzyl 5-phenyl-2-oxazolecarbamate (Ia) at 230 deg C gave benzyl alcohol and 2-phenyl-6-(5-phenyl-2-oxazolyl)-5H-oxazolotriazine-5,7(6H)-dione (IIIa).Compound IIIa was also obtained by heating the azide prepared from 5-phenyl-2-oxazolecarbohydrazide (IVa).In the same way, 2-methyl-6-(5-methyl-2-oxazolyl)-5H-oxazolotriazine-5,7(6H)-dione (IIIb) and 2-phenyl-6-(5-phenyl-2-thiazolyl)-5H-thiazolotriazine-5,7(6H)-dione (IIIc) were obtained from the corresponding hydrazides (IVb and IVc).Next, heating of benzyl 4-(2-phenylethyl)-allophanate (IIa) at 230 deg C gave cyanuric acid (VII), benzyl (2-phenylethyl)carbamate (VIII) and 1,3-bis(2-phenylethyl)-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (IX).Keywords - benzyl 2-oxazolecarbamate; benzyl 4-alkylallophanate; pyrolysis; 5H-oxazolotriazine-5,7(6H)-dione; 5H-thiazolotriazine-5,7(6H)-dione; ethyl 2-thiazolecarboxilate
- Tanaka, Chiaki,Nasu, Keiko,Yamamoto, Noriko,Shibata, Megumi
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p. 4195 - 4198
(2007/10/02)
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