Tetrahedron Letters

Editorial board ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23
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Graphical Contents List ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23
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Harry Herschal Wasserman December 1, 1920–December 29, 2013 ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): John L. Wood
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On the nature of the chain-extending species in organolithium initiated stereospecific reagent-controlled homologation reactions using α-chloroalkyl aryl sulfoxides ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Amanda L. Hoyt , Paul R. Blakemore The reaction of an organolithium with an α-chloroalkyl aryl sulfoxide ostensibly generates an α-chloroalkyllithium by sulfoxide–lithium exchange, but the actual identity of the chain-extending species in chlorosulfoxide-based StReCH reactions is not certain. To explore this issue, racemic 2-cyclohexyl (4R ∗ ,5R ∗ )-4,5-diphenyl-1,3,2-dioxaborolane was homologated by treatment with scalemic (S)-chloromethyl phenyl sulfoxide and n-BuLi (THF, −78°C). The reaction proceeded without a detectable level of kinetic resolution, a finding consistent with chloromethyllithium being the active chain-extending species rather than a chiral sulfurane intermediate. Graphical abstract image
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Highly functionalized donor–acceptor cyclopropanes applied toward the synthesis of the Melodinus alkaloids ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Alexander F.G. Goldberg , Robert A. Craig II , Nicholas R. O’Connor , Brian M. Stoltz A series of highly substituted vinylcyclopropanes were prepared and examined as reaction partners in a palladium-catalyzed (3+2) cycloaddition with nitrostyrenes. Described herein are our efforts to synthesize an elusive 1,1-divinylcyclopropane by several distinct approaches, and to apply surrogates of this fragment toward the synthesis of the Melodinus alkaloids. Graphical abstract image
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Total synthesis of nominal cyclocinamide B and investigation into the identity of the cyclocinamides ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Stephanie S. Curzon , Jessica M. Garcia , Joseph P. Konopelski The total synthesis of nominal cyclocinamide B, a cyclic peptide marine natural product, is reported together with an isomer of nominal cyclocinamide A. Initial attempts at the synthesis of the title compounds by inclusion of a turn inducer failed. However, a direct synthesis succeeded in the formation of the 14-membered cyclic peptide structure. A comparison of the data from all synthetic cyclocinamide A and B compounds with those of the natural products leads to the conclusion that the two natural products possess the same relative stereochemistry and that the true structures have not been defined. Graphical abstract image
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Electrophilic carbonyl activation: competing condensative cyclizations of tryptamine derivatives ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Fan Liu , Mohammad Movassaghi A series of tryptamine derived bisindole substrates were subjected to electrophilic activation of the functional grouping at their α-nitrogen in the form of iminium ions to enable cyclization onto the sterically hindered indole substructure. Our observations regarding divergent cyclization outcomes using electronically distinct bisindole substrates are described. Surprising preference for the Friedel–Crafts alkylation reaction and evidence for an intriguing reversible spirocyclization are discussed. Graphical abstract image
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Dimerization and comments on the reactivity of homophthalic anhydride ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Julia Hong , Zheng Wang , Aaron Levin , Thomas J. Emge , David M. Floyd , Spencer Knapp Homophthalic anhydride (HPA) dimerizes under the influence of base to provide, sequentially, the (3–4′)-C-acyl dimer, a pair of chiral diastereomeric bis(lactones), 3-(2-carboxybenzyl)isocoumarin-4-carboxylic acid, and finally, 3-(2-carboxybenzyl)isocoumarin. The structures of the bis(lactones) were misassigned in 1970 based on the (presumed) cis thermal decarboxylative elimination reaction of the lower melting one. The preferred pathway should be trans–anti, however, and crystallographic analysis of one of the bis(lactones) reverses the earlier assignment. The formal cycloaddition reaction of HPA with imines occurs in preference to HPA dimerization; the mechanistic implications of this reactivity difference are discussed. Graphical abstract image
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One-pot transformation of esters to analytically pure ketones: methodology and application in process development ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Anthony R. Prosser , Dennis C. Liotta A convenient, single-pot protocol for the transformation of esters into analytically pure ketones is described herein. This method circumvents the need for purification and affords near quantitative yields for all substrates investigated. As a test of its utility, the method is used to improve the yields of a process for preparing a pharmacologically relevant anti-HIV intermediate by nearly 10 fold. Graphical abstract image
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An improved method for the large scale preparation of α,α′-trehalose-6-phosphate ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Chunliang Liu , Patrick S. Mariano An improved method was developed for the efficient, large-scale synthesis of α,α′-trehalose-6-phosphate starting with α,α′-trehalose. In the sequence, octa-trimethylsilylation of α,α′-trehalose is followed by selective removal of the 6-O-trimethylsilyl protecting group. Reaction of the mono-alcohol with (PhO)2POCl is then followed by simultaneous hydrogenolysis and per-desilylation to generate α,α′-trehalose-6-phosphate, free of contamination by inorganic phosphate. Graphical abstract image
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A concise total synthesis of hymenialdisine ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Rahman Shah Zaib Saleem , Jetze J. Tepe The synthesis of hymenialdisine has offered challenges that included the formation of the regio-isomers upon monobromination, atom-scrambling in the cyclization step, and low to moderate yields in the last steps. We herein present a short and concise (6 overall steps), high yielding route (44% overall yields) for this biologically interesting natural product that addresses these issues and avoids the use of any protecting groups. Graphical abstract image
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SET-promoted photoaddition reactions of N-α-trimethylsilylmethyl-N,N-dibenzylamines with fullerene C60. Electronic factors that govern photoaddition efficiencies ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Suk Hyun Lim , Jinju Yi , Choon Sup Ra , Keepyung Nahm , Dae Won Cho , Ga Ye Lee , Jinheung Kim , Ung Chan Yoon , Patrick S. Mariano Single electron transfer (SET) promoted photoaddition reactions of N-α-trimethylsilylmethyl-N,N-dibenzylamines to fullerene C60 were investigated as part of an effort aimed at developing a general method to prepare various aryl ring containing aminomethylfullerenes and exploring factors that govern photoaddition efficiencies. The results show that the photoaddition reactions take place highly efficiently to form 1,2-adducts. The mechanism for this process involves generation of aminium radicals and C60 anion radical intermediates by a pathway initiated by excited state SET. SET is followed by desilylation of the aminium radicals to produce α-amino radicals that couple with either C60 or its radical anion to form precursors of the 1,2-adducts. The electronic nature of para-substituents on the aryl ring of N-α-trimethylsilylmethyl-N,N-dibenzylamines has a pronounced effect on the efficiency of the photoaddition reaction, with electron donating groups causing a greater than 2-fold enhancement compared to that brought about by electron withdrawing groups. Graphical abstract image
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Diastereoselective synthesis of anti-3-hydroxy-2-trifluoromethyl carboxylic acids ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): P. Veeraraghavan Ramachandran , Barnabas Otoo , Prem B. Chanda Unlike the hydrocarbon analogs, this first report of enolboration–aldolization of 3,3,3-trifluoropropanoic acid provides essentially pure anti-diastereomers of α-trifluoromethyl-β-hydroxy carboxylic acids in 77–90% yields. Graphical abstract image
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An unusual thermal oxidation of triaryloxazoles ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): James E. Pickett Triaryloxazoles undergo slow but smooth thermal oxidation at 135–175°C to produce nitrile and anhydride products apparently arising from endoperoxides formed from the addition of oxygen to the heterocyclic ring. The Hammett ρ value of ca. −0.7 and activation energy of ca. 87kJ/mol (21kcal/mol) seemed to rule out an electron-transfer mechanism. A mechanism involving a peroxidic biradical and a triplet to singlet spin flip is suggested. Graphical abstract image
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Synthesis of the cyclic prenylguanidine nitensidine E using a palladium-catalyzed carbenylative amination ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Mitsuru Kitamura , Ryohei Yuasa , David L. Van Vranken We demonstrate the utility of carbenylative aminations in the synthesis of the cyclic alkaloid nitensidine E involving both protected and un-protected guanidine moieties. The alkylguanidine substrate is generated using a Mitsunobu reaction and we show that NH chemical shifts correlate with the regiochemistry and tautomeric structure of N-alkyl-bis-N,N′-Boc-guanidines. When the doubly-protected guanidine is used as a substrate in the palladium reaction, the catalyst assembles the heterocyclic ring and quaternary center of nitensidine E but with concomitant loss of one of the Boc groups. The reaction also works with an un-protected guanidine leading directly to nitensidine E.
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Preparation and reactions of 4-iodobutyl pinacolborate. Synthesis of substituted alkyl and aryl pinacolboronates via 4-iodobutyl pinacolborate utilizing tetrahydrofuran as the leaving group ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Chris L. Murphy , Aaron Hall , Emily J. Roberts , Matthew D. Ryan , Jacob W. Clary , Bakthan Singaram Iodine reacts with 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (HBpin), under ambient reaction conditions in THF, to form the iodoalkylborate species 2-(4-iodobutoxy)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4-IboxBpin). Apparently, one-half equivalent of I2 reacts with HBpin to form IBpin in pentanes, which in turn cleaves THF to form the 4-IboxBpin. Alkyl and aryl Grignard reagents, prepared under Barbier conditions, then react with 4-IboxBpin to form the corresponding alkyl and aryl pinacolboronates while reforming and liberating THF as the leaving group. Graphical abstract image
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Design and synthesis of 7-naphthyl-8-aza-7-deaza-2′-deoxyadenosines as environmentally sensitive fluorescent nucleosides ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Yoshio Saito , Azusa Suzuki , Takumi Yamauchi , Isao Saito We synthesized various 7-naphthylated 8-aza-7-deaza-2′-deoxyadenosine derivatives 1a–d as environmentally sensitive fluorescent (ESF) nucleosides and investigated their photophysical properties. Among them, 1b and 1c showed solvatofluorochromic properties and were able to recognized thymine base by forming Watson–Crick base pair when incorporated in DNA. Using DNA probes containing 1b and 1c, the opposite thymine base in DNA duplex was discriminated by wavelength shift of the fluorescence emission. Graphical abstract image
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Oxazoles for click chemistry II: synthesis of extended heterocyclic scaffolds ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Pravin C. Patil , Frederick A. Luzzio , Donald R. Demuth New routes to 2,4,5-trisubstituted oxazoles were established whereby the substitution pattern was established by the structure of the starting nonsymmetrical acyloins. 2-Chloromethyl-4, 5-disubstituted oxazoles were prepared by refinements of an earlier described process whereby chloroacetyl esters of symmetrical and nonsymmetrical acyloins were cyclized using an ammonium acetate/acetic acid protocol. After substitution is effected, the azide moiety is then installed by substitution under mild conditions. While dibrominated and iodinated phenyloxazoles are required for further synthetic elaboration, the cyclization reaction was found to be very sensitive to the relative positions of the halogens in the starting materials. Graphical abstract image
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The chemistry of vicinal tricarbonyls: an expedient route to fully-substituted 3-aminopyrroles ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Phong M. Truong , Michael D. Mandler , Michael P. Doyle A one-pot, three-component reaction between a 2,3-diketoester, an imine, and an aldehyde, catalyzed by p-toluenesulfonic acid, produces fully-substituted 3-aminopyrroles that can be converted to pyrrolo[3,2-d]pyrimidine-2,4-dione. Graphical abstract image
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A new arylation of silyl enol ethers by quinone monoacetal substitution ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Toshifumi Dohi , Tohru Kamitanaka , Hitoho Takamuro , Yusuke Mishima , Naohiko Washimi , Yasuyuki Kita Quinone monoacetals (QMAs) were found to be convenient substrates for a unique arylation reaction of enol silyl ethers. This arylation process of QMAs typically proceeds through the acetal activation of the QMAs by a hydrogen-bond donor solvent, such as a fluoroalcohol, for the initiating step. The silyl transfer from silyl enol ethers to the carbonyl oxygen of the QMAs appears to be involved in the C–C coupling step, followed by QMA aromatization. By this method, valuable α-aryl carbonyl compounds containing o-phenol moieties can be obtained directly under mild conditions without lactone formation. Graphical abstract image
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First stereospecific total synthesis of (−)-affinisine oxindole as well as facile entry into the C(7)-diastereomeric chitosenine stereochemistry ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): German O. Fonseca , Zhi-Jian Wang , Ojas A. Namjoshi , Jeffrey R. Deschamps , James M. Cook The first synthesis of (−)-affinisine oxindole was completed in an enantiospecific fashion from commercially available d-(+)-tryptophan in 10% overall yield. The asymmetric Pictet–Spengler reaction, diastereospecific oxidative-rearrangement of a tetrahydro-β-carboline, and stereospecific enolate-mediated palladium-catalyzed cross coupling process were key steps in the sequence. This represents the first example of a total synthesis via stereospecific entry into either the alstonisine related or epimeric chitosenine related oxindole stereochemistry depending on the presence or absence of an N b-benzyl protecting group. Graphical abstract image
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Synthesis of (±)-tetramethoxy-sinensigenin A via an intramolecular Marson-type cyclization ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Aymara M.M. Albury , Dripta De Joarder , Michael P. Jennings The concise synthesis of (±)-tetramethoxy-sinensigenin A (2) is reported. The key C–C bond formation, which forged the [3.2.1]-bicyclic ether moiety, was the result of a regio- and diastereoselective intramolecular Marson-type cyclization via a pendent oxocarbenium cation intermediate. Graphical abstract image
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Synthesis and bioactivity of MSH4 oligomers prepared by an A2+B2 strategy ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Dilani Chathurika Dehigaspitiya , Suryakiran Navath , Craig S. Weber , Ronald M. Lynch , Eugene A. Mash Oligomers incorporating the tetrapeptide MSH4, the minimum active sequence of melanocyte stimulating hormone, were synthesized by an A2 +B2 strategy involving microwave-assisted copper-catalyzed azide-alkyne cycloaddition. A2 contained an MSH4 core while B2 contained a (Pro-Gly)3 spacer. Soluble mixtures containing compounds with up to eight MSH4 units were obtained from oligomerizations at high monomer concentrations. The avidities of several oligomeric mixtures were evaluated by means of a competitive binding assay using HEK293 cells engineered to overexpress the melanocortin 4 receptor. When based on total MSH4 concentrations, avidities were only minimally enhanced compared with a monovalent control. The lack of variation in the effect of ligands on probe binding is consistent with high off rates for MSH4 in both monovalent and oligomeric constructs relative to that of the competing probe. Graphical abstract image
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Access to drug metabolites via C–H functionalization: copper-catalyzed aerobic oxidation of N,N-dimethylalkylamines in complex pharmaceuticals ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Julien Genovino , Dalibor Sames , B. Barry Touré We aim the power of C–H bond functionalization at a problem of major practical consequence—namely, scalable access to drug metabolites and their analogs. In this context, we pursue the development of simple C–H oxidation methods that tolerate a wide range of functional groups and structural features found in pharmaceuticals (‘chemotransformations’). In this Letter, we focus on N,N-dimethylamines as they are frequently found in pharmaceuticals and undergo CYP-mediated N-demethylation reactions in vivo. The direct access to these in vivo metabolites, from the parent drugs, has remained a significant synthetic challenge for which a broad solution had not previously been found. We here show that a simple copper–oxygen catalytic system provides a scalable route to complex N-demethylated drug metabolites. Graphical abstract image
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Cinchonidinium acetate as a convenient catalyst for the asymmetric synthesis of cis-stilbenediamines ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Ryan R. Walvoord , Marisa C. Kozlowski Inexpensive and readily available cinchonidinium acetate is an effective catalyst for the syn-selective aza-Henry reaction of arylnitromethanes and aryl imines. The resulting masked cis-stilbenediamine products are produced in excellent diastereoselectivity and good enantioselectivity, and enantiopure material can be achieved via recrystallization. The features of the cinchona catalyst needed for selectivity are discussed, with specific emphasis on formation of a kinetically controlled syn-product without epimerization of the highly acidic α-nitro stereocenter. Graphical abstract image
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Nature loves nitrogen heterocycles ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Christopher T. Walsh Nitrogen-containing heterocycles are central to the chemical reactions that occur in all organisms. The metabolic transformation of amino acids into five, six, and seven-member heterocycles reveals the chemical logic and enzymatic machinery for shunting primary metabolites into bioactive heterocyclic nitrogen scaffolds. Graphical abstract image
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Trapping of Payne rearrangement intermediates with arylselenide anions ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Michael E. Jung , Daniel L. Sun The intermediate epoxy alcohols prepared via a Payne rearrangement can be trapped with arylselenide anions, giving mixtures of ring-opened products. The 1-arylseleno-2,3-diols are generally favored over the 3-arylseleno-1,2-diols in this process although the reaction of trisubstituted epoxyalcohols, for example, 17, differs from those of disubstituted epoxyalcohols, for example, 21. Graphical abstract image
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Contiguous radical pivaloyloxymethylation–directed C(sp3)–H iodination of N-tosyl cycloalkanecarbaldimine ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Shintaro Fujii , Mayu Nakano , Yousuke Yamaoka , Kiyosei Takasu , Ken-ichi Yamada , Kiyoshi Tomioka A reaction of N-tosyl cycloalkanecarbaldimines with iodomethyl pivalate was initiated by triethylborane to give pivaloyloxymethylated products bearing 3-iodocycloalkyl groups. Radical addition of pivaloyloxymethyl to imines generates aminyl radicals, which then regioselectively cleave CH bonds at the 3-position of the cycloalkane moieties. The resulting carbon-centered radicals are trapped with iodine. DFT calculations rationalized stereo- and regioselectivity. Graphical abstract image
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Silica gel-supported Brønsted acid: reactions in the column system ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Yasushi Shimoda , Hisashi Yamamoto Silica gel readily adsorbs strong Brønsted acids such as bis(trifluoromethanesulfonyl) imide (Tf2NH) to afford a heterogeneous supported catalyst that enables various acid-promoted reactions. The catalyst was recovered by means of easy filtration and reused for three successive runs. In addition, various acid-promoted reactions proceed smoothly with the reaction column system packed within silica gel-supported Brønsted acid. Graphical abstract image
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FeCl3-catalyzed selective acylation of amines with 1,3-diketones via C–C bond cleavage ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Sinan Wang , Yang Yu , Xuyun Chen , Haipan Zhu , Peile Du , Guohua Liu , Liguang Lou , Hao Li , Wei Wang We describe a novel FeCl3 catalyzed selective acylation of amines involving the C–C bond cleavage of simple 1,3-diketones. The process proceeds efficiently under a neat condition to give structurally diverse amides. Notably, the acylation process displays high selectivity toward amines over hydroxyl functionality. Traditionally difficult aromatic amines and sterically demanding disubstituted amines can engage in the process with high efficiency. Graphical abstract image
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Synthesis of anti-inflammatory α-and β-linked acetamidopyranosides as inhibitors of toll-like receptor 4 (TLR4) ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Peter Wipf , Benjamin R. Eyer , Yukihiro Yamaguchi , Feng Zhang , Matthew D. Neal , Chhinder P. Sodhi , Misty Good , Maria Branca , Thomas Prindle Jr. , Peng Lu , Jeffrey L. Brodsky , David J. Hackam The low-molecular weight isopropyl 2-acetamido-α-glucoside 16 (C34) inhibits toll-like receptor 4 (TLR4) in enterocytes and macrophages in vitro, and reduces systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. We used a copper(II)-mediated solvolysis of anomeric oxazolines and an acid-mediated conversion of β-glucosamine and β-galactosamine pentaacetates to generate analogs of 16 at the anomeric carbon and at C-4 of the pyranose ring. These compounds were evaluated for their influence on TLR4-mediated inflammatory signaling in cultured enterocytes and monocytes. Their efficacy was confirmed using a NF-kB-luciferase reporter mouse, thus establishing the first structure–activity relationship (SAR) study in this series and identifying the more efficacious isopropyl 2-acetamido-α-galactoside 17. Graphical abstract image
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A five-membered lactone prodrug of CBI-based analogs of the duocarmycins ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Mika Uematsu , Daniel M. Brody , Dale L. Boger The preparation, characterization, and examination of the CBI-based 5-membered lactone 5 capable of serving as a prodrug or protein (antibody) conjugation reagent are disclosed along with its incorporation into the corresponding CC-1065 and duocarmycin analog 6, and the establishment of their properties. Graphical abstract image
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Stereocontrolled intramolecular iron-mediated tandem [6+2]-ene-type diene/dienol ether double cyclization reactions ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Anthony J. Pearson , Sheng Zhang A stereocontrolled intramolecular iron-mediated diene/diene tandem double cyclocoupling reaction has been explored using vinyl ethers as the olefin partners. Diastereomerically pure spirotricyclic products with functionalized (alkoxymethyl) side chains can be formed efficiently under photothermal conditions. With a methoxy substituent on the iron-complexed cyclohexadiene core, demetallation and acidic hydrolysis of the cyclocoupling product afforded a cyclohexenone ring. Graphical abstract image
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From fragments to leads: novel bacterial NAD+-dependent DNA ligase inhibitors ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Michael R. Hale , Claire Brassington , Dan Carcanague , Kevin Embrey , Charles J. Eyermann , Robert A. Giacobbe , Lakshmaiah Gingipalli , Madhusudhan Gowravaram , Jenna Harang , Tina Howard , Georgine Ioannidis , Haris Jahic , Amy Kutschke , Valerie A. Laganas , James Loch , Matthew D. Miller , Kerry E. Murphy-Benenato , Herbert Oguto , Ludovic Otterbein , Sahil Joe Patel , Adam B. Shapiro , P. Ann Boriack-Sjodin Bacterial NAD+-dependent DNA ligase (LigA) is an essential enzyme involved in the repair, replication, and recombination of DNA in all bacteria, making it an attractive target in antibacterial drug discovery. A novel series of LigA inhibitors was discovered by combining information from fragment-based lead generation, X-ray crystal structures of previously discovered inhibitors bound to the adenosine binding site of LigA bound to and established structure–activity relationships of LigA inhibitors. The compounds described here were evaluated in a variety of Gram-positive and Gram-negative pathogens as well as evaluation of physical properties. Graphical abstract image
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Propylphosphonic anhydride (T3P) mediated synthesis of β-lactams from imines and aryl-substituted acetic acids ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Graeme Coulthard , William P. Unsworth , Richard J.K. Taylor β-Lactams were prepared from imines and aryl-substituted acetic acids using T3P as an activating agent. In most cases, good to excellent yields were obtained (up to 93%) and the trans-β-lactam was the exclusive or major diastereoisomer (confirmed through analysis of 1H NMR coupling constants and by X-ray crystallography). Graphical abstract image
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Isomerization of coencapsulated molecules ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Kang-da Zhang , Julius Rebek Jr. A cylindrical capsule host, held together by hydrogen bonds, takes up guests with polar solvent molecules. The arrangements and motions of molecules in the host’s space are deduced from NMR experiments. Graphical abstract image
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Total synthesis of clavosolide A via tandem allylic oxidation/oxa-conjugate addition reaction ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Joseph B. Baker , Hyoungsu Kim , Jiyong Hong The tandem allylic oxidation/oxa-conjugate addition reaction promoted by the gem-disubstituent effect in conjunction with the NHC-mediated oxidative esterification was explored for the facile synthesis of clavosolide A. Graphical abstract image
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The total synthesis of (+)-elaeokanidine A: natural product or isolation artefact? ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): James D. Cuthbertson , William P. Unsworth , Catherine L. Moody , Richard J.K. Taylor The first total synthesis of (+)-elaeokanidine A is reported. The synthesis features a formic acid-mediated cyclisation to access the indolizidine core and a double conjugate addition of ammonia to construct the piperidone unit. On the basis of 1H NMR spectroscopic data, the relative stereochemistry of elaeokanidine A has been confirmed. Two isomeric species were also formed during the piperidone ring construction, which are potentially elaeokanidines B and C, although their structures could not be assigned unambiguously. The synthetic transformations used to prepare these products are analogous to conditions employed during the extraction procedure, raising questions about the true origins of these compounds. Graphical abstract image
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Rhodium(II) catalyzed cyclopropanation/cycloaddition reactions of the bis(diazo)piperidin-2-one system ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Sara A. Bonderoff , Albert Padwa Bis(diazo)piperidin-2-ones that are devoid of a donor substituent in the 4-position undergo a one-pot cyclopropanation/cascade dipole formation/cycloaddition reaction to produce novel azapolycycles. Graphical abstract image
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Iododemetallation of potassium organotrifluoroborates and tributylarylstannanes using sodium iodide/iron(III) chloride ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): David W. Blevins , Min-Liang Yao , Li Yong , George W. Kabalka A combinative iron(III) chloride/sodium iodide system was found to be very efficient for the iododemetallation of both organotrifluoroborates and tributyl(aryl)stannanes. A variety of functional groups tolerate the mild reaction conditions. Graphical abstract image
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Pd-catalyzed cascade cyclization of o-alkynylarylbromides with dialkylalkynes via consecutive carbopalladation ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Jian Zhao , Naoki Asao , Yoshinori Yamamoto , Tienan Jin A novel Pd-catalyzed cascade cyclization of o-alkynylarylbromides with dialkylalkynes for the construction of the multisubstituted dihydrocyclopenta[a]indene derivatives has been reported. The reaction proceeds efficiently through a four consecutive carbopalladations with alkyne and alkene moieties. Graphical abstract image
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Temperature dependence of turnover in a Sc(OTf)3-catalyzed intramolecular Schmidt reaction ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Charlie Fehl , Erin E. Hirt , Sze-Wan Li , Jeffrey Aubé The intramolecular Schmidt reaction of ketones and tethered azides is an efficient method for the generation of amides and lactams. This reaction is catalyzed by Lewis acids, which tightly bind the strongly basic amide product and result in product inhibition. We report herein conditions to achieve a catalytic Schmidt reaction using substoichiometric amounts of the heat-stable Lewis acid Sc(OTf)3. This species was shown to effectively release products of the Schmidt reaction in a temperature-dependent fashion. Thus, heat was able to promote catalyst turnover. A brief substrate scope was conducted using these conditions. Graphical abstract image
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Diastereoselective synthesis of a hydroxamate containing bicyclo-[3.2.0] β-lactam aminal via ruthenium alkene isomerization and Pd(II)-catalyzed oxidative amidation ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Maria O. Jobbins , Mark W. Majewski , Allen G. Oliver , Marvin J. Miller With antibiotic resistance on the rise, the need for new medicinal scaffolds is needed. The synthesis of an aminal bicyclic β-lactam core is described. The key synthetic step is Pd(II)-catalyzed oxidative amidation. The product is a single diastereomer, confirmed by X-ray crystallography. Graphical abstract image
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Ruthenium-catalyzed rearrangement of propargyl sulfoxides: formation of α,β-unsaturated thioesters ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Renhua Zheng , Youliang Wang , Liming Zhang Our previously developed strategy of generating ketene intermediates via Ru-catalyzed intramolecular oxidation of terminal alkynes is applied to propargyl sulfoxides. The reaction undergoes interesting further rearrangement upon the ketene generation to afford α,β-unsaturated thioesters in good to excellent yields in the reported cases. Graphical abstract image
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The Rügheimer–Burrows reaction revisited: facile preparation of 4-alkylisoquinolines and 3,5-dialkylpyridines from (partially) saturated amines ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Alena Yu. Platonova , Daniel Seidel A long-known class of cyclic amine/aldehyde condensation reactions was reinvestigated. Benzoic acid was found to efficiently promote condensations of amines such as piperidine or 1,2,3,4-tetrahydroisoquinoline with aromatic aldehydes, resulting in amine β-functionalization and aromatization. These redox-neutral transformations provide 3,5-dialkylpyridines and 4-alkylisoquinolines in moderate to good yields, following short reaction times under microwave conditions. Graphical abstract image
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Studies toward the synthesis of cinachyramine. An efficient route to 1,5-diazabicyclo[4.4.0]dec-5-enes ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Olga V. Barykina-Tassa , Barry B. Snider Hydrogenation (3atm) of readily available pyrido[1,2-a]pyrimidines 10, 14, and 17 over 5% Rh/Al2O3 forms 1,5-diazabicyclo[4.4.0]dec-5-enes 9, 15, and 18 in >95% yield, providing a general route to this little-studied class of compounds. All attempts to form the tetrahydro-1,2,4-triazine moiety of cinachyramine (1) by rearrangement of amidinium dimethylhydrazone 8 using the procedures developed by Kamatori to convert hydrazone 3a to tetrahydro-1,2,4-triazine 4a were unsuccessful. Graphical abstract image
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Synthesis and reactivity of anthracenyl-substituted arenediynes ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Gavvalapalli Nagarjuna , Yi Ren , Jeffrey S. Moore Cyclization reaction pathways of aryl-substituted arenediynes depend on the interplay between the steric interactions and electronic properties of the aryl substituents. Herein, to further probe the impact of bulky and electron rich aryl substituents on the cyclization of arenediynes, anthracenyl-substituted arenediynes (1–3) with different ortho substituents were synthesized and their thermal, photo, and radical initiated cyclization reactions were studied. Graphical abstract image
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Spirastrellolide E: synthesis of an advanced C(1)–C(24) southern hemisphere ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Alexander Sokolsky , Xiaozhao Wang , Amos B. Smith III The synthesis of a C(1)–C(24) advanced southern hemisphere fragment towards the total synthesis of spirastrellolide E has been achieved. Highlights of the route include a highly convergent Type I Anion Relay Chemistry (ARC) tactic for fragment assembly, in conjunction with a directed, regioselective gold-catalyzed alkyne functionalization to generate the central unsaturated [6,6]-spiroketal. Graphical abstract image
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A Zincke aldehyde approach to gelsemine ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Jonathan K. Lam , Scott B. Joseph , Christopher D. Vanderwal We have developed a Zincke-aldehyde-based approach to the complex alkaloid gelsemine. It features a key thermal pericyclic cascade that converts a Zincke aldehyde bearing a pendant alkene into a hydroisoindolone product that shares many structural features with the target molecule. Our efforts to convert these intermediates to gelsemine are also discussed. Graphical abstract image
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SN2 displacement at the quaternary carbon center: a novel entry to the synthesis of α,α-disubstituted α-amino acids ()
Publication date: 3 June 2015 Source:Tetrahedron Letters, Volume 56, Issue 23 Author(s): Kotaro Ishihara , Hiromi Hamamoto , Masato Matsugi , Takayuki Shioiri A novel method for the SN2 reaction on quaternary carbon atoms using bis(p-nitrophenyl)phosphorazidate has been developed. Chiral tertiary alcohols were directly converted into the corresponding chiral tertiary azides with complete inversion of configuration. Several α,α-disubstituted α-amino esters or amino acids were prepared through the conversion of azides to the corresponding amines by catalytic hydrogenation. Graphical abstract image
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