- Lithiation-Substitution of N -Boc-2-phenylazepane
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Preparation of 2,2-disubstituted azepanes was accomplished from N - tert -butoxy(N -Boc)-2-phenylazepane by treatment with butyllithium then electrophilic quench. The lithiation was followed by in situ ReactIR spectroscopy and the rate of rotation of the carbamate was determined by variable temperature (VT)-NMR spectroscopy and by DFT studies. Most electrophiles add α to the nitrogen atom but cyanoformates and chloroformates gave ortho -substituted products. Cyclic carbamates were formed from an aldehyde or ketone electrophile. Kinetic resolution with sparteine was only poorly selective. Removal of the Boc group promoted cyclization to a homoindolizidine or an isoindolinone.
- Aeyad, Tahani,Williams, Jason D.,Meijer, Anthony J. H. M.,Coldham, Iain
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- Unexpected Rearrangement of N-Allyl-2-phenyl-4,5-Dihydrooxazole-4-Carboxamides to Construct Aza-Quaternary Carbon Centers
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The unexpected rearrangement of N-allyl-2-phenyl-4,5-dihydrooxazole-4-carboxamides in the presence of LiHMDS has been found. The key features are: (1) the net reaction consisted of 1,3-migration of the N-allyl group, (2) the rearrangement produced a congested aza-quaternary carbon center, (3) both cyclic and acyclic substrates underwent the unexpected rearrangement to afford products in moderate to high yields, and (4) the reaction seemed to be highly stereoselective. In addition, a plausible mechanism has been discussed.
- Choi, Goyeong,Jo, Seoyoung,Mun, Juyeon,Jeong, Yonguk,Kim, Seok-Ho,Jung, Jong-Wha
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- TMSOTf-mediated approach to 1,3-oxazin-2-one skeleton through one-pot successive reduction-[4 + 2] cyclization process of imides with ynamides
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A one-pot approach to access functionalized 1,3-oxazin-2-one skeleton has been developed through successive reduction and subsequent [4 + 2] cyclization process of N-Boc lactams with ynamides by TMSOTf. As a result, a number of five to seven membered ring fused bicyclic [1,2-c][1,3]oxazin-1-ones 12a-m and tricyclic derivatives 13a-f were obtained in moderate to excellent yields with excellent regioselectivities. Moreover, linear N-Boc amides 9a-e were also amenable to this transformation, and the desired 3,4-dihydro-1,3-oxazin-2-ones 14a-m were readily achieved in moderate yields with excellent regioselectivities.
- Zhang, Chen-Chen,Huo, Zhi-Peng,Tang, Mei-Lin,Liang, Yong-Xi,Sun, Xun
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supporting information
(2021/03/15)
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- Decarboxylative Oxygenation via Photoredox Catalysis
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The direct conversion of aliphatic carboxylic acids to their dehomologated carbonyl analogues has been accomplished through photocatalytic decarboxylative oxygenation. This transformation is applicable to an array of carboxylic acid motifs, producing ketones, aldehydes, and amides in excellent yields. Preliminary results demonstrate that this methodology is further amenable to aldehyde substrates via in situ oxidation to the corresponding acid and subsequent decarboxylative oxygenation. We have exploited this strategy for the sequential oxidative dehomologation of linear aliphatic chains.
- Faraggi, Tomer M.,Li, Wei,MacMillan, David W. C.
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p. 410 - 415
(2019/12/24)
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- Ball-milling enables highly selective solvent-free N-tert-butoxycarbonylation for activation of amides
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A ball-milling enabled chemoselective activation of amides via N-tert-butoxycarbonylation catalyzed by 4-dimethylaminopyridine is described under solvent-free conditions. High chemoselectivity with respect to NH acidity of amides has been observed. A one-pot two-step procedure for selective esterification of amides has been demonstrated in model reaction of benzamides with p-cresol and benzyl alcohol.
- Shi, Weijia,Sun, Guoping,Zou, Gang
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supporting information
(2020/07/03)
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- Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation
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Selective clearance of senescent cells (SCs) has emerged as a potential therapeutic approach for age-related diseases, as well as chemotherapy- and radiotherapy-induced adverse effects. Through a cell-based phenotypic screening approach, we recently identified piperlongumine (PL), a dietary natural product, as a novel senolytic agent, referring to small molecules that can selectively kill SCs over normal or non-senescent cells. In an effort to establish the structure-senolytic activity relationships of PL analogues, we performed a series of structural modifications on the trimethoxyphenyl and the α,β-unsaturated δ-valerolactam rings of PL. We show that modifications on the trimethoxyphenyl ring are well tolerated, while the Michael acceptor on the lactam ring is critical for the senolytic activity. Replacing the endocyclic C2–C3 olefin with an exocyclic methylene at C2 render PL analogues 47–49 with increased senolytic activity. These α-methylene containing analogues are also more potent than PL in inducing ROS production in WI-38 SCs. Similar to PL, 47–49 reduce the protein levels of oxidation resistance 1 (OXR1), an important oxidative stress response protein that regulates the expression of a variety of antioxidant enzymes, in cells. This study represents a useful starting point toward the discovery of senolytic agents for therapeutic uses.
- Liu, Xingui,Wang, Yingying,Zhang, Xuan,Gao, Zhengya,Zhang, Suping,Shi, Peizhong,Zhang, Xin,Song, Lin,Hendrickson, Howard,Zhou, Daohong,Zheng, Guangrong
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p. 3925 - 3938
(2018/06/19)
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- Chemoenzymatic Synthesis of Substituted Azepanes by Sequential Biocatalytic Reduction and Organolithium-Mediated Rearrangement
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Enantioenriched 2-aryl azepanes and 2-arylbenzazepines were generated biocatalytically by asymmetric reductive amination using imine reductases or by deracemization using monoamine oxidases. The amines were converted to the corresponding N′-aryl ureas, which rearranged on treatment with base with stereospecific transfer of the aryl substituent to the 2-position of the heterocycle via a configurationally stable benzyllithium intermediate. The products are previously inaccessible enantioenriched 2,2-disubstituted azepanes and benzazepines.
- Zawodny, Wojciech,Montgomery, Sarah L.,Marshall, James R.,Finnigan, James D.,Turner, Nicholas J.,Clayden, Jonathan
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supporting information
p. 17872 - 17877
(2019/01/04)
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- One-Pot Reductive Allylation of Amides by Using a Combination of Titanium Hydride and an Allylzinc Reagent: Application to a Total Synthesis of (-)-Castoramine
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A one-pot direct reductive allylation protocol has been developed for the synthesis of secondary amines by using titanium hydride and an allylzinc reagent. This protocol is applicable to a broad range of substrates, including acyclic amides, benzamides, α,β-unsaturated amides, and lactams. The stereochemical outcome obtained from the reaction with crotylzinc reagent suggested that the allylation reaction proceeds through a six-membered cyclic transition state. A total synthesis of (-)-castoramine was accomplished by following this protocol for the highly stereoselective construction of contiguous stereocenters.
- Itabashi, Suguru,Shimomura, Masashi,Sato, Manabu,Azuma, Hiroki,Okano, Kentaro,Sakata, Juri,Tokuyama, Hidetoshi
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supporting information
p. 1786 - 1790
(2018/07/03)
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- Heterocyclyl Tetracyclines. 1. 7-Trifluoromethyl-8-Pyrrolidinyltetracyclines: Potent, Broad Spectrum Antibacterial Agents with Enhanced Activity against Pseudomonas aeruginosa
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Utilizing a total synthesis approach, the first 8-heterocyclyltetracyclines were designed, synthesized, and evaluated against panels of tetracycline- and multidrug-resistant Gram-positive and Gram-negative pathogens. Several compounds with balanced, highly potent in vitro activity against a broad range of bacterial isolates were identified through structure-activity relationships (SAR) studies. One compound demonstrated the best antibacterial activity against Pseudomonas aeruginosa both in vitro and in vivo for tetracyclines reported to date.
- Deng, Yonghong,Sun, Cuixiang,Hunt, Diana K.,Fyfe, Corey,Chen, Chi-Li,Grossman, Trudy H.,Sutcliffe, Joyce A.,Xiao, Xiao-Yi
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p. 2498 - 2512
(2017/04/03)
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- COMPOSITIONS AND METHODS FOR SELECTIVELY DEPLETING SENESCENT CELLS
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The present disclosure provides compositions and methods for selectively killing senescent cells, wherein the composition comprises piperlongumine (PL) or derivative thereof. The selective killing of senescent cells may delay aging and/or treat age-related disorders.
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Paragraph 0442-0443
(2016/02/26)
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- Unusual skeletal rearrangement of unsaturated seven-membered lactams into fused pyrrolidinolactones
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Unsaturated ε-lactams undergo a novel process involving a skeletal reorganization to give fused pyrrolidine-lactones by reaction with aromatic α-bromo ketones in the presence of 1,4-diazabicyclo[2.2.2]octane and a base. The process involves the formation
- Alvarez, Silvia,Dominguez, Gema,Gradillas, Ana,Perez-Castells, Javier
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p. 3094 - 3102
(2013/06/27)
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- TETRACYCLINE ANALOGS
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The present invention is directed to a compound represented by Structural Formula (I), or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (I) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (I) and its therapeutic use.
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Page/Page column 147
(2012/03/09)
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- Hydrozirconation of four-, five-, six- and seven-membered N-alkoxycarbonyl lactams to lactamols
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A general, practical, and efficient reduction of four-, five-, six- and, seven-membered N-alkoxycarbonyl lactams to the aldehyde oxidation state is reported. The reduction methodology involves the hydrozirconation reaction by Cp2Zr(H)Cl under m
- Piperno, Anna,Carnovale, Caterina,Giofr, Salvatore V.,Iannazzo, Daniela
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supporting information; experimental part
p. 6880 - 6882
(2012/02/05)
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- Phosphinates as new electrophilic partners for cross-coupling reactions
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The use of enol phosphinates as electrophiles for cross-coupling reactions has been explored. Both boronic acids (Suzuki-Miyaura reaction) and stannanes (Stille reaction) couple efficiently with lactam derived phosphinates. The 2008 Royal Society of Chemi
- Guo, Jun,Harling, John D.,Steel, Patrick G.,Woods, Tom M.
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experimental part
p. 4053 - 4058
(2009/06/28)
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- A One-Pot Process for the Enantioselective Synthesis of Amines via Reductive Amination under Transfer Hydrogenation Conditions
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(Equation presented) Cyclic amines may be prepared via a sequence of deprotection followed by intramolecular reductive amination of t-Boc-protected amino ketones under asymmetric transfer hydrogenation conditions. In cases where the corresponding imine reaction proceeds with high enantioselectivity, this is reflected in the one-step process.
- Williams, Glynn D.,Pike, Richard A.,Wade, Charles E.,Wills, Martin
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p. 4227 - 4230
(2007/10/03)
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- Palladium-catalyzed coupling of vinyl phosphates with aryl or heteroaryl boronic acids. Application to the synthesis of substituted nitrogen containing heterocycles
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Substituted nitrogen-containing heterocycles were prepared in three steps from commercially available derivatives via an extension of the Suzuki reaction involving the palladium-catalyzed coupling of vinyl phosphates with aryl or heteroaryl boronic acids.
- Lepifre, Franck,Clavier, Sylvain,Bouyssou, Pascal,Coudert, Gérard
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p. 6969 - 6975
(2007/10/03)
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- Cyclic amidino agents useful as nitric oxide synthase inhibitors
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The current invention discloses useful amidino derivative useful as nitric oxide synthase inhibitors.
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- Rhodium carbenoid mediated cyclisations. Part 3. Synthesis of cyclic ethers from lactones
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Ethyl lithiodiazoacetate ring opens lactones, N-Boc lactams, and cyclic anhydrides and carbonates to give ω-functionalised α-diazo-β- keto esters in varying yield (Tables 1 and 2). Thus simple 5-, 6-, 7-, and 8-membered lactones react to give α,ω-diazo alcohols, and benzo-fused lactones give diazo phenols. The corresponding reaction with N-Boc lactams gives Boc-amino diazo compounds, and cyclic anhydrides give α,ω-diazo carboxylic acids. Treatment of the diazo compounds derived from 5-, 6-, and 7-membered lactones with a catalytic amount of rhodium(II) acetate resulted in rhodium carbenoid mediated cyclisation to give 6-, 7-, and 8-membered cyclic ethers (Table 3). Attempted preparation of larger rings, however, resulted in formation of cyclopentanones by competing C-H insertion reactions. Similarly, the Boc-protected amino diazo compounds only gave the products of C-H insertion on treatment with rhodium(II) acetate.
- Moody, Christopher J.,Taylor, Roger J.
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p. 721 - 731
(2007/10/02)
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- Organometallic Ring-Opening Reactions of N-Acyl and N-Alkoxycarbonyl Lactams. Synthesis of Cyclic Imines
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The reactions of hexyl- and phenylmagnesium bromides with N-acyl and N-alkoxycarbonyl lactams in tetrahydrofuran at -78 deg C have been performed to determine the factors affecting the regioselectivity.N-Pivaloyl γ- and δ-lactams undergo the ring-opening reactions with both Grignard reagents, whereas on the N-benzoyl γ-lactam a complete selectivity is achieved only with phenylmagnesium bromide.The N-Cbz γ- and δ-lactams preferentially react at the exocyclic carbonyl group, especially with hexylmagnesium bromide.The N-Boc five- to eight-membered lactams undergo the ring-opening reaction to give N-Boc-ω-amino ketones, although the efficiency slightly decreases by increasing the ring size.The deprotection of the N-Boc-ω-amino ketones with trifluoroacetic acid easily affords the corresponding five- to seven-membered cyclic imines.Pyridine alkaloids containing the cyclic imine moiety have been prepared by a modified route, exploiting the more easily available pyridyllithium reagents, instead of the corresponding Grignard reagents.
- Giovannini, Arianna,Savoia, Diego,Umani-Ronchi, Achille
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p. 228 - 234
(2007/10/02)
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