- Ultrasound promoted environmentally benign, highly efficient, and chemoselective N-tert-butyloxycarbonylation of amines by reusable sulfated polyborate
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The sulfated polyborate catalyzed an efficient and chemoselective N-tert-butyloxycarbonylation of amines under ultrasonic irradiation is developed. A broad substrate scope has been demonstrated for N-Boc protection of various primary/secondary amines. It allows converting several aliphatic/aryl/heteroaryl amines, amino alcohol, aminoester, and chiral amines to their N-Boc-protected derivatives under solvent-free conditions with excellent yields. The protocol has several advantages such as easy catalyst, and product isolation, short reaction time, excellent yields, outstanding chemoselectivity, and catalyst recyclability, among others. This makes the process practicable, economical, and environmentally benign.
- Pise, Ashok S.,Ingale, Ajit P.,Dalvi, Navnath R.
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supporting information
p. 3768 - 3780
(2021/10/26)
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- Thiamine hydrochloride as a recyclable organocatalyst for the efficient and chemoselective N-tert-butyloxycarbonylation of amines
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Thiamin hydrochloride promoted highly efficient and ecofriendly approach has been described for the chemoselective N-tert-butyloxycarbonylation of amines under solvent-free conditions at ambient temperature. The demonstrated approach has been applicable for the N-Boc protection of variety of aliphatic, aryl, heteroaryl amines. The chemoselective protection of amino group occurs in chiral amines and amino alcohol without racemization in high yield. Thiamin hydrochloride is stable, economical, easy to handle and environmentally friendly.
- Ingale, Ajit P.,Garad, Dnyaneshwar N.,Ukale, Dattatraya,Thorat, Nitin M.,Shinde, Sandeep V.
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supporting information
p. 3791 - 3804
(2021/11/04)
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- Sulfated tungstate: A highly efficient, recyclable and ecofriendly catalyst for chemoselective N-tert butyloxycarbonylation of amines under the solvent-free conditions
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Sulfated tungstate catalyzed an efficient and ecofriendly protocol has been described for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions at room temperature. The variety of functionalized aliphatic, aromatic and heteroaromatic amines efficiently undergoes the N-tert-butyloxycarbonylation under the developed protocol. The aminoalcohol, aminophenol, aminoester as well as various chiral amines underwent the chemoselective N-Boc protection under the optimized reaction condition. The rapid reaction rate, mild conditions, very good functional group tolerance, excellent yield, solvent-free, easy recovery products and excellent catalyst recyclability are the advantages of this protocol. This makes the protocol feasible, economical and environmentally benign.
- Ingale, Ajit P.,Shinde, Sandeep V.,Thorat, Nitin M.
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supporting information
p. 2528 - 2543
(2021/07/02)
-
- Nanoceria as an efficient and green catalyst for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions
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Nanocerium oxide mediated an efficient and green protocol has been described for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions at ambient temperature. Various aliphatic, aromatic and heteroaromatic amines were protected using developed protocol and several functional groups such as alcohol, phenol and ester were well tolerated under these conditions. The rapid reaction rate, mild conditions, very good functional group tolerance, excellent yield, solvent-free, easy recovery products and excellent catalyst recyclability are the advantages of this protocol. This makes the protocol feasible, economical and environmentally benign.
- Garad, Dnyaneshwar N.,Ingale, Ajit P.,Shinde, Sandeep V.,Ukale, Dattatraya
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supporting information
p. 1656 - 1668
(2021/04/05)
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- Enantio- And regioselective asymmetric allylic substitution using a chiral aminophosphinite ruthenium complex: an experimental and theoretical investigation
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The design and synthesis of a new chiral aminophosphinite-ligated ruthenium complex is described. The ruthenium complex, [Ru(AMP)2(CH3CN)2][BPh4]2{AMP = (S)-tert-butyl 1-(diphenylphosphinooxy)-3-methylbutan-2-ylcarbamate}, has been found to catalyze nucleophilic addition of phenol and carboxylic acid to allyl chloride in a highly regioselective fashion with enantiomeric excess ranging from 12 to 90.
- Das, Dhiraj,Jena, Rajesh K.
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p. 39319 - 39327
(2021/12/24)
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- Structural Basis for α-Helix Mimicry and Inhibition of Protein–Protein Interactions with Oligourea Foldamers
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Efficient optimization of a peptide lead into a drug candidate frequently needs further transformation to augment properties such as bioavailability. Among the different options, foldamers, which are sequence-based oligomers with precise folded conformation, have emerged as a promising technology. We introduce oligourea foldamers to reduce the peptide character of inhibitors of protein–protein interactions (PPI). However, the precise design of such mimics is currently limited by the lack of structural information on how these foldamers adapt to protein surfaces. We report a collection of X-ray structures of peptide–oligourea hybrids in complex with ubiquitin ligase MDM2 and vitamin D receptor and show how such hybrid oligomers can be designed to bind with high affinity to protein targets. This work should enable the generation of more effective foldamer-based disruptors of PPIs in the context of peptide lead optimization.
- Cussol, Léonie,Mauran-Ambrosino, Laura,Buratto, Jérémie,Belorusova, Anna Y,Neuville, Maxime,Osz, Judit,Fribourg, Sébastien,Fremaux, Juliette,Dolain, Christel,Goudreau, Sébastien R.,Rochel, Natacha,Guichard, Gilles
-
supporting information
p. 2296 - 2303
(2020/12/07)
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- Urea based foldamers
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N,N′-linked oligoureas are a class of enantiopure, sequence-defined peptidomimetic oligomers without amino acids that form well-defined and predictable helical structures akin to the peptide α-helix. Oligourea-based foldamers combine a number of features—such as synthetic accessibility, sequence modularity, and folding fidelity—that bode well for their use in a range of applications from medicinal chemistry to catalysis. Moreover, it was recently recognized that this synthetic helical backbone can be combined with regular peptides to generate helically folded peptide-oligourea hybrids that display additional features in terms of helix mimicry and protein-surface recognition properties. Here we provide detailed protocols for the preparation of requested monomers and for the synthesis and purification of homo-oligoureas and peptide-oligourea hybrids.
- Yoo, Sung Hyun,Li, Bo,Dolain, Christel,Pasco, Morgane,Guichard, Gilles
-
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- O-Alkyl S-(Pyridin-2-yl)carbonothiolates: Operationally Simple and Highly Nitrogen-Selective Reagents for Alkoxy Carbonylation of Amino Groups
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Amino groups are selectively protected in good yields by reaction with O-Alkyl S-(pyridin-2-yl)carbonothiolates in an appropriate solvent at room temperature in air. Even glucosamine, which contains multiple hydroxyl groups, is selectively N-protected in methanol.
- Hashimoto, Yoshimitsu,Morita, Nobuyoshi,Suzuki, Tomoyuki,Tamura, Osamu,Tanaka, Kosaku
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p. 899 - 902
(2020/05/28)
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- Synthesis and photophysics of benzazole based triazoles with amino acid-derived pendant units. Multiparametric optical sensors for BSA and CT-DNA in solution
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Herein we report the synthesis of a series of amino acid-derived triazoles by an organocatalytic cycloaddition reaction between azides and carbonyl compounds, catalyzed by a simple amine. These compounds present absorption maxima located in the UV-B ascribed to fully spin and symmetry allowed electronic transitions and a main fluorescence emission in the UV-A (~380 nm) with a relatively large Stokes shift (5700 cm?1). No significant solvatochromism was observed in both ground and excited states. Unexpectedly, the benzoxazole derivatives presented much higher fluorescence quantum yield values (40–80%) of compared to the sulfur analogues (3–6%). In addition, the DNA binding assays indicated that these compounds presented strong interaction with CT-DNA, which could be attributed to π-stacking and intermolecular hydrogen-bonding. The interaction of the benzazoles with bovine serum albumin (BSA) was also investigated, where a suppression mechanism was observed. In each case, docking was performed to better understand the observed interactions.
- Debia, Natalí P.,Rodríguez, Juan J.P.,da Silveira, Carolina H.,Chaves, Otavio A.,Iglesias, Bernardo A.,Rodembusch, Fabiano S.,Lüdtke, Diogo S.
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-
- N-1 BRANCHED ALKYL ETHER SUBSTITUTED IMIDAZO[4,5-C]QUINOLINE COMPOUNDS, COMPOSITIONS, AND METHODS
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Imidazo[4,5-c]quinoline compounds having a substituent that is attached at the N-1 position by a branched group, single enantiomers of the compounds, pharmaceutical compositions containing the compounds, and methods of making the compounds are disclosed. Methods of use of the compounds as immune response modifiers, for inducing cytokine biosynthesis in humans and animals, and in the treatment of diseases including infectious and neoplastic diseases are also disclosed.
- -
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Page/Page column 36-37
(2020/06/19)
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- N-1 BRANCHED ALKYL SUBSTITUTED IMIDAZO[4,5-C]QUINOLINE COMPOUNDS, COMPOSITIONS, AND METHODS
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Imidazo[4,5-c]quinoline compounds having a substituent that is attached at the N-1 position by a branched group, single enantiomers of the compounds, pharmaceutical compositions containing the compounds, and methods of making the compounds are disclosed. Methods of use of the compounds as immune response modifiers, for inducing (or inhibiting) cytokine biosynthesis in humans and animals, and in the treatment of diseases including infectious and neoplastic diseases are also disclosed.
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Page/Page column 45
(2020/12/29)
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- Design, synthesis, and structure-activity relationship studies of L-amino alcohol derivatives as broad-spectrum antifungal agents
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To discover broad spectrum antifungal agents, two strategies were applied, and a novel class of L-amino alcohol derivatives were designed and synthesized. 3-F substituted compounds 14i, 14n, 14s and 14v exhibited excellent antifungal activities with broad antifungal spectra against C. albicans and C. tropicalis, with MIC values in the range of 0.03–0.06 μg/mL, and against A. fumigatus and C. neoformans, with MIC values in the range of 1–2 μg/mL. Notably, Compounds 14i, 14n, 14s and 14v also displayed moderate activities against fluconazole-resistance strains 17# and CaR that were isolated from AIDS patients. Moreover, only compounds in the S-configuration showed antifungal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 14v stemmed from inhibition of C. albicans CYP51. Compounds 14n and 14v were almost nontoxic to mammalian A549 cells, and their stability in human plasma was excellent.
- Zhao, Liyu,Tian, Linfeng,Sun, Nannan,Sun, Yin,Chen, Yixuan,Wang, Xinran,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
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p. 374 - 385
(2019/06/05)
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- Synthesis of Amino Acid-Derived 1,2,3-Triazoles: Development of a Nontrivial Fluorescent Sensor in Solution for the Enantioselective Sensing of a Carbohydrate and Bovine Serum Albumin Interaction
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A series of amino acid-derived 1,2,3-triazoles presenting the amino acid and the aromatic moieties connected by a triazole-4-carboxylate spacer is discussed in this work. These compounds were achieved in good yields by organocatalytic enamine-azide [3 + 2] cycloadditions. One of the molecules obtained, bearing a 7-chloroquinoline moiety, was photoactive in the UV-violet region and was successfully employed as a probe for substrate-specific enantiomeric sensing using d-(-)-arabinose and l-(+)-arabinose. The potential application as a fluorescent probe to detect protein in phosphate buffer solution was also explored using as model bovine serum albumin (BSA). The studied compounds presented both suppression and association behavior in the presence of BSA. In addition, theoretical calculations were performed at levels ωB97XD/cc-pVDZ and PBE1PBE/6-311+G(d,p) together with the polarizable continuum model to understand the interaction of the molecules with the enantiomers.
- Debia, Natalí P.,Saraiva, Maiara T.,Martins, Bruna S.,Beal, Roiney,Gon?alves, Paulo F. B.,Rodembusch, Fabiano S.,Alves, Diego,Lüdtke, Diogo S.
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p. 1348 - 1357
(2018/02/09)
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- Synthesis of Enantiomerically Pure 3-Substituted Piperazine-2-acetic Acid Esters as Intermediates for Library Production
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The piperazine heterocycle is broadly exploited in FDA-approved drugs and biologically active compounds, but its chemical diversity is usually limited to ring nitrogen substitutions, leaving the four carbon atoms underutilized. Using an efficient six-step synthesis, chiral amino acids were transformed into 3-substituted piperazine-2-acetic acid esters as diastereomeric mixtures whose cis and trans products (dr 0.56 a? 2.2:1, respectively) could be chromatographically separated. From five amino acids (both antipodes) was obtained a complete matrix of 20 monoprotected chiral 2,3-disubstituted piperazines, each as a single absolute stereoisomer, all but one in multigram quantities. In keeping with our overall purpose of constructing more Csp3-enriched compound libraries for drug discovery, these diverse and versatile piperazines can be functionalized on either nitrogen atom, allowing them to be used as scaffolds for parallel library synthesis and as intermediates for the production of novel piperazine compounds.
- Reddy Guduru, Shiva Krishna,Chamakuri, Srinivas,Raji, Idris O.,MacKenzie, Kevin R.,Santini, Conrad,Young, Damian W.
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p. 11777 - 11793
(2018/09/27)
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- Conformational properties of ascydiacyclamide analogues with cyclic α-amino acids instead of oxazoline residues
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Ascidiacyclamide [ASC, cyclo(-Ile-oxazoline-D-Val-thiazole-)2] is a cyclic octapeptide isolated from tunicates. We designed ASC analogues [cyclo(-Ile-Xxx-D-Val-thiazole-)2] in which Pro or a homologue was substituted for oxazoline: [Pro]ASC (Xxx: proline), [Aze]ASC (Xxx: (S)-Azetidine-2-carboxylic acid), [Pip]ASC (Xxx: (S)-Piperidine-2-carboxylic acid) and [ΔPro]ASC (Xxx: (S)-3-pyrroline-2-carboxylic acid) to explore their potential to serve as substitutes for the oxazoline ring. The conformations of these analogues were examined using X-ray diffraction, 1H NMR and CD spectroscopy. In both the crystal and solution states, the conformations of [Pro]ASC, [Aze]ASC and [ΔPro]ASC were novel square structures having two trans imide bonds and stabilized by two intramolecular hydrogen bonds. The crystal structure of [Pip]ASC was a folded conformation with cis and trans imide bonds. Three isomers (cc, ct and tt) were present in a solution of [Pip]ASC. From crystal structures, the degree of puckering in the side chains of Pro and its homologues was estimated to be in the order Pip > Pro > Aze > ΔPro. [Pro]ASC and [Pip]ASC showed strong cytotoxicity, but [Aze]ASC and [ΔPro]ASC showed no cytotoxicity. Among the four analogues, there is consistency between the prolyl ring puckering and cytotoxicity, but not between the peptide backbone structure and cytotoxicity.
- Asano, Akiko,Numata, Shohei,Yamada, Takeshi,Minoura, Katsuhiko,Doi, Mitsunobu
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supporting information
p. 6554 - 6562
(2017/11/09)
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- Copper nanoparticles catalyzed N-H functionalization: An efficient solvent-free N-tert-butyloxycarbonylation strategy
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A chemoselective transformation of amines to their tert-butyloxycarbonyl (Boc) protected derivatives (NBoc) is described using Cu-NPs under solvent-free conditions. Simple method, rapid reaction rate, mild conditions, tolerance of a wide range of functional groups, excellent yield, ease recovery and high catalytic turnover are the salient features of this approach. tert-Butyloxycarbonylation of chiral amino acid esters and amino alcohols were performed without racemization.
- Deb, Barnali,Debnath, Sudipto,Deb, Anindita,Maiti, Dilip K.,Majumdar, Swapan
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supporting information
p. 629 - 633
(2017/01/25)
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- A new family of 1,2,3-oxathiazolidine-2,2-dioxide phosphonate derivatives: Synthesis, characterization and anticancer evaluation
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An efficient synthesis of a new series of organophosphorus compounds having a cyclic sulfamidates moiety is described. The cyclic sulfamidate precursors were prepared from α-amino acids after four steps (Reduction, N-Boc protection, cyclization and cleavage). The novel organophosphonates were synthesized within two steps starting from the cyclic sulfamidate (chloroacetylation following by phosphorylation via Arbuzov reaction). A particular compound 7-a (diethyl phosphonate {2-[(4S)-4-benzyl-1,2,3-oxathiazolidin-3-yl-2,2-dioxyde]-2-oxoethyl}) was essayed for their in vitro cytotoxic activities against a panel of four cell lines (Jurkat, K562, U266, and A431). For all of these cells, the synthesized compound showed low cytotoxicity, even at high concentration levels (4?mM).
- K'tir, Hacène,Aouf, Zineb,Souk, Tan Otea,Zerrouki, Rachida,Berredjem, Malika,Aouf, Nour-Eddine
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p. 555 - 559
(2017/05/01)
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- General, Auxiliary-Enabled Photoinduced Pd-Catalyzed Remote Desaturation of Aliphatic Alcohols
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A general, efficient, and site-selective visible light-induced Pd-catalyzed remote desaturation of aliphatic alcohols into valuable allylic, homoallylic, and bis-homoallylic alcohols has been developed. This transformation operates via a hybrid Pd-radical mechanism, which synergistically combines the favorable features of radical approaches, such as a facile remote C-H HAT step, with that of transition-metal-catalyzed chemistry (selective β-hydrogen elimination step). This allows achieving superior degrees of regioselectivity and yields in the desaturation of alcohols compared to those obtained by the state-of-the-art desaturation methods. The HAT at unactivated C(sp3)-H sites is enabled by the easily installable/removable Si-auxiliaries. Formation of the key hybrid alkyl Pd-radical intermediates is efficiently induced by visible light from alkyl iodides and Pd(0) complexes. Notably, this method requires no exogenous photosensitizers or external oxidants.
- Parasram, Marvin,Chuentragool, Padon,Wang, Yang,Shi, Yi,Gevorgyan, Vladimir
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supporting information
p. 14857 - 14860
(2017/10/31)
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- ALPHA-OXOACYL AMINO-CAPROLACTAM DERIVATIVE
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The purpose of the present invention is to provide a pharmaceutical composition that is useful for the treatment of diseases that are caused by an increase in bone resorption and that does not cause serious side effects even when used in combination with another drug. The present invention relates to: an α-oxoacyl aminocaprolactam derivative that is represented by formula (I) (in the formula, X is —O— or —N(R1)— and R1 represents an alkoxycarbonyl group having 1-10 carbon atoms); and a bone resorption inhibitor containing the α-oxoacyl aminocaprolactam derivative.
- -
-
Paragraph 0179; 0180; 0181
(2016/06/06)
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- ALPHA-OXOACYL AMINO-CAPROLACTAM BODY
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The purpose of the present invention is to provide a pharmaceutical composition that is useful for the treatment of diseases that are caused by an increase in bone resorption and that does not cause serious side effects even when used in combination with another drug. The present invention relates to: an α-oxoacyl amino-caprolactam that is represented by formula (I) (in formula (I), X represents N or CH, Y represents O or CH2, and Z represents S or CH2); and a bone resorption inhibitor containing the α-oxoacyl amino-caprolactam.
- -
-
Paragraph 0173
(2016/06/06)
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- Chemo- and Diastereoselective N-Heterocyclic Carbene-Catalyzed Cross-Benzoin Reactions Using N-Boc-α-amino Aldehydes
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N-Boc-α-amino aldehydes are shown to be excellent partners in cross-benzoin reactions with aliphatic or heteroaromatic aldehydes. The chemoselectivity of the reaction and the facial selectivity on the amino aldehyde allow cross-benzoin products to be obtained in good yields and good diastereomeric ratios. The developed method is utilized as the key step in a concise total synthesis of d-arabino-phytosphingosine.
- Haghshenas, Pouyan,Gravel, Michel
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supporting information
p. 4518 - 4521
(2016/09/28)
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- COMBINATIONS OF HEPATITIS C VIRUS INHIBITORS
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The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein.
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Page/Page column 487; 488
(2015/02/02)
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- Tunable Bifunctional Phosphine-Squaramide Promoted Morita-Baylis-Hillman Reaction of N-Alkyl Isatins with Acrylates
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A series of highly tunable bifunctional phosphine-squaramide H-bond donor organocatalysts 6 has been synthesized from inexpensive and commercially available β-amino alcohols in moderate yields. Catalyst 6 can efficiently promote the asymmetric Morita-Baylis-Hillman (MBH) reaction of N-alkyl isatins with acrylate esters providing the chiral 3-substituted 3-hydroxy-2-oxindoles in good yields and enantioselectivities (up to 93 yield and 95 ee), in which the challenging substrate tert-butyl acrylate 9d, provided the best ee value to date. Moreover, this methodology was applied successfully in the synthesis of chiral cyclic spiropyrrolizidineoxindole and γ-butyrolactone derivatives without enantioselectivity deterioration. The possible mechanism of this MBH reaction was also investigated by 31PNMR, ESI-MS and KIE studies. The KIE experiments show that the electrophilic addition of N-methyl isatin to the complex of acrylate ester and phophine-squaramide is the rate-determing step of the asymmetric MBH reaction.
- Dong, Ze,Yan, Chao,Gao, Yongzhi,Dong, Chune,Qiu, Guofu,Zhou, Hai-Bing
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p. 2132 - 2142
(2015/06/23)
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- A multifaceted secondary structure mimic based on piperidine-piperidinones
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Minimalist secondary structure mimics are typically made to resemble one interface in a protein-protein interaction (PPI), and thus perturb it. We recently proposed suitable chemotypes can be matched with interface regions directly, without regard for secondary structures. Here we describe a modular synthesis of a new chemotype 1, simulation of its solution-state conformational ensemble, and correlation of that with ideal secondary structures and real interface regions in PPIs. Scaffold 1 presents amino acid side-chains that are quite separated from each other, in orientations that closely resemble ideal sheet or helical structures, similar non-ideal structures at PPI interfaces, and regions of other PPI interfaces where the mimic conformation does not resemble any secondary structure. 68 different PPIs where conformations of 1 matched well were identified. A new method is also presented to determine the relevance of a minimalist mimic crystal structure to its solution conformations. Thus dld-1-faf crystallized in a conformation that is estimated to be 0.91 kcal-mol-1 above the minimum energy solution state. Do we know, when designing a new peptidomimetic scaffold like the one shown, how it can resemble secondary structures? Design and modular synthesis of this elongated mimic is reported, and the structure is related to ideal and real structures at PPI interfaces.
- Xin, Dongyue,Perez, Lisa M.,Ioerger, Thomas R.,Burgess, Kevin
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supporting information
p. 3594 - 3598
(2014/04/17)
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- A rapid entry to amino acid derived diverse 3,4-dihydropyrazines and dihydro[1,2,3]triazolo[1,5-a]pyrazines through 1,3-dipolar cycloaddition
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An efficient, general and practical synthesis of diverse 3,4-dihydropyrazines, 6,7-dihydro-[1,2,3]triazolopyrazines and 7,8-dihydro-[1,2,3]triazolodiazepines through intramolecular 1,3-dipolar cycloaddition from amino acid derived common intermediates with high yields is described. Moreover, one-pot access to optically active 3-aryl substituted 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazines in the palladium-copper co-catalytic system has also been achieved in this work. The easy substrate availability and operational simplicity make the process suitable for further exploration. This journal is the Partner Organisations 2014.
- Bera, Saurav,Panda, Gautam
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p. 3976 - 3985
(2014/06/09)
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- Synthesis of iron P-N-P' and P-NH-P asymmetric hydrogenation catalysts
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Complexes of the type mer,trans-[Fe(P-N-P)(CO)2Br]BF4 are known to be precatalysts for the asymmetric direct hydrogenation of ketones and imines. Employing related ligand scaffolds, we successfully generated and tested the series of three new precatalysts [Fe(PCy2CH2CH-NCH(R)CH2PPh2)(CO)2Br]BF4 with chirality derived from (S)-amino alcohols with phenyl, benzyl, and isopropyl substituents (R), yielding fairly active and selective systems. For the reduction of acetophenone to (S)-1-phenylethanol turnover frequencies up to 920 h-1 and up to 74% enantiomeric excess at 50 °C and 5-25 atm of H2 were obtained. We found, however, that placing these large groups R next to nitrogen was found to be deleterious to catalytic activity. Extending the scope of the ligand structure, we then developed a series of six P-N-P and five P-NH-P systems starting with o-diphenylphosphinobenzaldehyde and the phosphine-amines PPh2CHR1CHR2NH2 (R1 = H, Ph, CH2Ph, iPr with R2 = H or R1 = Me, Ph with R2 = Ph) as well as their corresponding [Fe(P-N-P)(NCMe)3][BF4]2 and [Fe(P-NH-P)(NCMe)3][BF4]2 complexes, which were not catalytically active. Finally, we made the new achiral iron complex mer,cis-Fe(PPh2(o-C6H4)CHNCH2CH2PPh2)(CO)Br2, which was active for the direct hydrogenation of acetophenone, achieving turnover frequencies of 800 h-1 at 50°C and 25 atm of H2.
- Sonnenberg, Jessica F.,Lough, Alan J.,Morris, Robert H.
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supporting information
p. 6452 - 6465
(2015/02/19)
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- A simple, rapid, and efficient N-Boc protection of amines under ultrasound irradiation and catalyst-free conditions
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A green and simple approach for the N-Boc protection on structurally diverse amines under ultrasound irradiation is described. Selective N-Boc protection was achieved in excellent isolated yield in a short reaction time at room temperature. Mild conditions, inexpensive and an easily available reagent, and absence of any auxiliary substances are the main advantages of this procedure. Graphical abstract: [Figure not available: see fulltext.]
- Amira, Aicha,K'Tir, Hacene,Berredjem, Malika,Aouf, Nour-Eddine
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p. 509 - 515
(2014/03/21)
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- Explorations of an intramolecular route to pyrrolo[3,4-b]isoxazoles: An unexpected retro-Claisen reaction
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Potential precursors have been prepared for intramolecular 1,3-dipolar cycloaddition to form a pyrrolo[3,4-b]isoxazole. The cycloaddition has not to date been accomplished, however an unexpected retro-Claisen reaction is reported. ARKAT-USA, Inc.
- Jones, Raymond C.F.,Law, Carole C.M.,Elsegood, Mark R.J.
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- Tetrahydroquinoline-derived macrocyclic toolbox: The discovery of antiangiogenesis agents in zebrafish assay
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A novel approach to incorporate the macrocyclic rings onto the privileged substructure, i.e., tetrahydroquinoline scaffold, is developed. The presence of an amino acid-derived moiety in the macrocyclic skeleton provides an opportunity to modulate the nature of the chiral side chain. Further, evaluation in a zebrafish screen identified three active small molecules (2.5b, 3.2d, and 4.2) as antiangiogenesis agents at 2.5 μM.
- Reddy Guduru, Shiva Krishna,Chamakuri, Srinivas,Chandrasekar, Gayathri,Kitambi, Satish Srinivas,Arya, Prabhat
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supporting information
p. 666 - 670
(2013/07/26)
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- Building a macrocyclic toolbox from C-linked carbohydrates identifies antiangiogenesis agents from zebrafish assay
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We report the synthesis of four different types of macrocyclic-derived glycohybrids from carbohydrates that have an amino acid moiety in the large-ring skeleton. These macrocyclic glycohybrids were obtained from α-C-1H- and β-C-1H-linked carbohydrates. In one series, we utilized ring-closing metathesis as the "stitching technology" to obtain two different macrocycles, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The click approach was the key reaction in our second series to obtain two other macrocyclic compounds, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Interestingly, in both cases, the macrocyclic compounds that have a cis relationship (i.e., axial-axial orientation) between C-1H and C-5H showed activity and their other diastereomers (i.e., equatorial-axial C-1H and C-5 H) with a trans relationship did not show any effect. The synthesis of four different types of macrocyclic glycohybrids that contain an amino acid moiety in the large-ring skeleton is reported. Ring-closing metathesis and click chemistry approaches were utilized to obtain two different series of macrocycles. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Copyright
- Jogula, Srinivas,Dasari, Bhanudas,Khatravath, Mahender,Chandrasekar, Gayathri,Kitambi, Satish Srinivas,Arya, Prabhat
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supporting information
p. 5036 - 5040
(2013/11/06)
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- β3R3-Peptides: Design and synthesis of novel peptidomimetics and their self-assembling properties at the air-water interface
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In this study we present the design and synthesis of a novel class of peptidomimetics, the β3R3-peptides. Via alternating directions of the amide bonds along β-peptide sequences, β3R3-peptides can potentially extend the structural space available to β-peptidic foldamers. Detailed analysis at the air-water interface shows strand conformations and the formation of sheet assemblies with different degrees of crystallinity. Furthermore β3R3-peptides exhibit a high proteolytic stability thus making them an interesting new class of peptidomimetics for biomedical applications. The Royal Society of Chemistry.
- Mosca, Simone,Dannehl, Claudia,M?ginger, Uwe,Brezesinski, Gerald,Hartmann, Laura
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supporting information
p. 5399 - 5403
(2013/09/02)
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- A mild multistep conversion of n-protected α-amino acids into N-protected β3-amino acids utilizing the Nef reaction
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Current methods of homologation of α-amino acids to β-amino acids have limitations. To overcome these shortfalls the Nef reaction has been utilized in the multistep synthesis of β3-amino acids from α-amino acids. In this approach, N-protected a
- Sleebs, Brad E.,Nguyen, Nghi H.,Hughes, Andrew B.
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supporting information
p. 747 - 751
(2013/05/08)
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- Copper(I)/ABNO-catalyzed aerobic alcohol oxidation: Alleviating steric and electronic constraints of Cu/TEMPO catalyst systems
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Cu/TEMPO catalyst systems promote efficient aerobic oxidation of sterically unhindered primary alcohols and electronically activated substrates, but they show reduced reactivity with aliphatic and secondary alcohols. Here, we report a catalyst system, consisting of (MeObpy)CuI(OTf) and ABNO (MeObpy =4,4′-dimethoxy-2,2′-bipyridine; ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl), that mediates aerobic oxidation of all classes of alcohols, including primary and secondary allylic, benzylic, and aliphatic alcohols with nearly equal efficiency. The catalyst exhibits broad functional group compatibility, and most reactions are complete within 1 h at room temperature using ambient air as the source of oxidant.
- Steves, Janelle E.,Stahl, Shannon S.
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supporting information
p. 15742 - 15745
(2013/11/06)
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- Catalyst-controlled C-O versus C-N allylic functionalization of terminal olefins
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The divergent synthesis of syn-1,2-aminoalcohol or syn-1,2-diamine precursors from a common terminal olefin has been accomplished using a combination of palladium(II) catalysis with Lewis acid cocatalysis. Palladium(II)/bis-sulfoxide catalysis with a silver triflate cocatalyst leads for the first time to anti-2-aminooxazolines (C-O) in good to excellent yields. Simple removal of the bis-sulfoxide ligand from this reaction results in a complete switch in reactivity to afford anti-imidazolidinone products (C-N) in good yields and excellent diastereoselectivities. Mechanistic studies suggest the divergent C-O versus C-N reactivity from a common ambident nucleophile arises due to a switch in mechanism from allylic C-H cleavage/functionalization to olefin isomerization/oxidative amination.
- Strambeanu, Iulia I.,White, M. Christina
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supporting information
p. 12032 - 12037
(2013/09/02)
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- RTD-1 mimic containing γPNA scaffold exhibits broad-spectrum antibacterial activities
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Macrocyclic peptides with multiple disulfide cross-linkages, such as those produced by plants and those found in nonhuman primates, as components of the innate immunity, hold great promise for molecular therapy because of their broad biological activities
- Rapireddy, Srinivas,Nhon, Linda,Meehan, Robert E.,Franks, Jonathan,Stolz, Donna Beer,Tran, Dat,Selsted, Michael E.,Ly, Danith H.
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supporting information; experimental part
p. 4041 - 4044
(2012/04/10)
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- Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 2: α-Branched quaternary amines
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We report the synthesis and biological evaluation of a series of novel α-branched pyrazinoyl quaternary amines for their ability to block ion transport via the epithelial sodium channel (ENaC) in human bronchial epithelial cells (HBECs). Compound 12g has an IC50 of 30 nM and is highly efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 1 μg kg-1 at 1 h. In addition the SAR results demonstrate for the first time the chiral nature of the binding site of human ENaC. As such, pyrazinoyl quaternary amines represent a promising new class of ENaC blockers for the treatment of cystic fibrosis that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride.
- Hunt, Thomas,Atherton-Watson, Hazel C.,Collingwood, Stephen P.,Coote, Kevin J.,Czarnecki, Sarah,Danahay, Henry,Howsham, Catherine,Hunt, Peter,Paisley, Derek,Young, Alice
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scheme or table
p. 2877 - 2879
(2012/05/20)
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- Catalytic asymmetric [4+2] annulation initiated by an aza-rauhut-currier reaction: Facile entry to highly functionalized tetrahydropyridines
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Under control: The first example of chiral amino phosphine catalysts for the title reaction between vinyl ketones and N-sulfonyl-1-aza-1,3-dienes has been developed. Under ambient conditions, this protocol provides straightforward access to densely functionalized, enantioenriched tetrahydropyridines with high levels of sterecontrol in good to excellent yields. Copyright
- Shi, Zugui,Yu, Peiyuan,Loh, Teck-Peng,Zhong, Guofu
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supporting information; scheme or table
p. 7825 - 7829
(2012/09/08)
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- Synthesis of imidacloprid derivatives with a chiral alkylated imidazolidine ring and evaluation of their insecticidal activity and affinity to the nicotinic acetylcholine receptor
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A series of imidacloprid (IMI) derivatives with an alkylated imidazolidine ring were asymmetrically synthesized to evaluate their insecticidal activity against adult female housefly, Musca domestica, and affinity to the nicotinic acetylcholine receptor of the flies. The bulkier the alkyl group, the lower was the receptor affinity, but the derivatives methylated and ethylated at the R-5-position of the imidazolidine ring were equipotent to the unsubstituted compound. Quantitative structure-activity relationship (QSAR) analysis of the receptor affinity demonstrated that the introduction of a substituent into the imidazolidine ring was fundamentally disadvantageous, but the introduction of a substituent at the R-5-position was permissible in the case of its small size. The binding model of the synthesized derivatives with the receptor supported the QSAR analysis, indicating the existence of space for a short alkyl group around the R-5-position in the ligand-binding site. In addition, positive correlation was observed between the insecticidal activity and receptor affinity, suggesting that the receptor affinity was the primary factor in influencing the insecticidal activity even if the imidazolidine ring was modified.
- Nishiwaki, Hisashi,Kuriyama, Mituhiro,Nagaoka, Hikaru,Kato, Akira,Yamauchi, Satoshi,Shuto, Yoshihiro,Akamatsu, Miki
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p. 6305 - 6312,8
(2012/12/11)
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- Aziridine-2-carboxaldehyde dimers undergo homo-Ugi 4-component-5-center reactions
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Dimeric α-aziridine aldehydes have been used as the aldehyde component in Ugi and Passerini reactions. The highly reactive mixed anhydride intermediate is subject to nucleophilic attack by the aziridine, leading to homo-Ugi' β-acylaziridinyl-α-aminoamides. The products can be readily transformed into substituted lactones. Georg Thieme Verlag Stuttgart ? New York.
- Rotstein, Benjamin H.,Yudin, Andrei K.
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p. 2851 - 2858
(2012/11/07)
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- A facile synthesis and crystallographic analysis of N-protected β-amino alcohols and short peptaibols
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A facile, efficient and racemization-free method for the synthesis of N-protected β-amino alcohols and peptaibols using N-hydroxysuccinimide active esters is described. Using this method, dipeptide, tripeptide and pentapeptide alcohols were isolated in high yields. The conformations in crystals of β-amino alcohol, dipeptide and tripeptide alcohols were analysed, with a well-defined type III β-turn being observed in the tripeptide alcohol crystals. This method is found to be compatible with Fmoc-, Boc- and other side-chain protecting groups.
- Jadhav, Sandip V.,Bandyopadhyay, Anupam,Benke, Sushil N.,Mali, Sachitanand M.,Gopi, Hosahudya N.
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supporting information; experimental part
p. 4182 - 4187
(2011/06/28)
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- Enantioselective preparation of P-chiral phosphine oxides
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A highly efficient chiral auxiliary-based strategy for the asymmetric synthesis of P-chiral phosphine oxides in >98:2 er has been developed. The methodology involves the highly stereoselective formation of P-chiral oxazolidinones that then undergo displacement with a variety of Grignard reagents to prepare the desired phosphine oxides.
- Adams, Harry,Collins, Rebecca C.,Jones, Simon,Warner, Christopher J. A.
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supporting information; experimental part
p. 6576 - 6579
(2012/01/15)
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- 2,2-difunctionalization of alkenes via Pd(II)-catalyzed aza-Wacker reactions
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N-Ts and N-Boc derivatives of 1,2-diamines and 1,2-amino alcohols are shown to undergo efficient Pd(II)-catalyzed aza-Wacker reactions with a large range of electron-deficient alkenes. The resulting enamine intermediate generally undergoes cyclization with the second heteroatom to form 1,3-heterocycles. The sequence facilitates the rapid synthesis of saturated oxazolidines, imidazolidines, and their derivatives. Use of N-l-valinol derivatives results in highly diastereoselective reactions, where the net stereochemical outcome diverges between N-Ts and N-Boc.
- Elliott, Luke D.,Wrigglesworth, Joe W.,Cox, Brian,Lloyd-Jones, Guy C.,Booker-Milburn, Kevin I.
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supporting information; experimental part
p. 728 - 731
(2011/04/25)
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- A homogeneous catalyst for reduction of optically active esters to the corresponding chiral alcohols without loss of optical purities
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A ruthenium complex was found to catalyze the hydrogen reduction of esters under mild and neutral conditions. A variety of optically active esters can be reduced to the corresponding alcohols in excellent yield without loss of their optical purity or causing undesirable side reactions. Hydrogen reduction needs such simple operations - reaction, concentration, and purification - that the violent quench step and extraction step, which accompany conventional sodium borohydride or lithium aluminum hydride reduction, can be omitted.
- Kuriyama, Wataru,Ino, Yasunori,Ogata, Osamu,Sayo, Noboru,Saito, Takao
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supporting information; experimental part
p. 92 - 96
(2010/06/17)
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- Addition of allylzinc to a-amino acid-derived imines: Synthesis of diamino alcohols by Hydroboration
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Imines obtained by condensation of Z-pro- tected or Boc-protected α-amino aldehydes with α-amino tert-butyl esters or with O-silyl-protected amino alcohols were reacted with preformed allyl zinc yielding homoal- lylamines with yields around 50% and selectivities ranging from 50:50 to 90:10. Hydroboration of the terminal double bond furnished diamino alcohols with yields up to 97%. The configuration of the substrates was determined by X-ray-crystallographic analysis of a hydroboration product and comparison of physical data. Springer-Verlag 2010.
- Virlouvet, Mickael,Goesmann, Helmut,Feldmann, Claus,Podlech, Joachim
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experimental part
p. 177 - 198
(2010/08/05)
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- Synthesis of chiral aminophosphines from chiral aminoalcohols via cyclic sulfamidates
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(Chemical Equation Presented) Protic aminophosphines with multiple chiral centers were synthesized in good yields and high purity by the nucleophilic ring-opening of N-protected cyclic sulfamidates with metal phosphides, followed by hydrolysis and deprote
- Guo, Rongwei,Lu, Shuiming,Chen, Xuanhua,Tsang, Chi-Wing,Jia, Wenli,Sui-Seng, Christine,Amoroso, Dino,Abdur-Rashid, Kamaluddin
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supporting information; experimental part
p. 937 - 940
(2010/05/02)
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- Discovery of novel P3 sulfonamide-capped inhibitors of HCV NS3 protease. Inhibitors with improved cellular potencies
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Hepatitis C Virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 200 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-α or PEG-interferon alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only ~50% of the patients showing sustained virological response. We recently disclosed the discovery of Boceprevir, SCH 503034 (1), which is a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been shown to be efficacious in humans and is currently undergoing clinical trials. As second generation compounds, we have further explored various novel structures with the aim of improving enzyme and cellular binding activities of 1. Herein, we disclose our efforts toward the identification of a novel P3 sulfonamide-capped inhibitor that demonstrated improved binding and cellular activity compared to 1. X-ray structure of one of these inhibitors bound to the enzyme revealed a hydrogen bond of the P3 sulfonamide group to Cys-159 which resulted in improved binding and cellular potency.
- Venkatraman, Srikanth,Blackman, Mellissa,Wu, Wanli,Nair, Latha,Arasappan, Ashok,Padilla, Angela,Bogen, Stéphane,Bennett, Frank,Chen, Kevin,Pichardo, John,Tong, Xiao,Prongay, Andrew,Cheng, Kuo-Chi,Girijavallabhan, Viyyoor,George Njoroge
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experimental part
p. 4486 - 4495
(2009/10/10)
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- Synthesis of novel N-protected β3-amino nitriles: study of their hydrolysis involving a nitrilase-catalyzed step
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Several commercially available nitrilases were investigated with regard to their potential to hydrolyze N-protected β3-amino nitriles into their corresponding N-protected β3-amino acids. The biotransformations were obtained in different proportions depending on the nitrilase involved. The best hydrolysis results were achieved for the N-Cbz-β3-amino nitrile from l-alanine using the NIT-107, in a phosphate buffer at 0.05 M. However, no biotransformation into the corresponding acids was observed for the N-sulfonylamide β3-amino nitriles. Two simple and efficient procedures to prepare the β3-amino nitriles from their analogous α-amino acids are described. Thirty four new substances were synthesized and characterized over the course of this work.
- Veitia, Maite Sylla-Iyarreta,Brun, Pierre Louis,Jorda, Pierre,Falguieres, Annie,Ferroud, Clotilde
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scheme or table
p. 2077 - 2089
(2010/03/04)
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- Syntheis of new chiral 5,6,7,8-tetrahydrotetrazolo[1,5-a]pyrazines from α-amino acid derivatives following "click" chemistry
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An efficient and practical synthesis of new chiral fused tetrazoles have been synthesized following [3+2] cycloaddition reaction starting from α-amino acid derivatives.
- Mohapatra, Debendra K.,Maity, Pradip K.,Ghorpade, Ravindra V.,Gurjar, Mukund K.
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body text
p. 865 - 872
(2010/09/16)
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- Efficient and selective cleavage of the t-butoxycarbonyl group from di-t-butylimidodicarbonate using catalytic bismuth(III) bromide in acetonitrile
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Di-t-butylimidodicarbonates can be chemoselectively and efficiently deprotected to the corresponding mono-BOC-protected amines in high yields using a catalytic amount of bismuth(III) bromide in acetonitrile at room temperature. This method is mild and compatible with the presence of a wide range of functional and other protecting groups in the substrates, such as TBDMS, MOM and mono-BOC or Cbz-protected amines, etc. The method has advantages of ease of operation and use of nontoxic and inexpensive catalyst.
- Zheng, Jianlong,Yin, Biaolin,Huang, Wenming,Li, Xiaopeng,Yao, Hequan,Liu, Zhaogui,Zhang, Jiancun,Jiang, Sheng
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scheme or table
p. 5094 - 5097
(2009/12/01)
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- Functional analysis of an aspartate-based epoxidation catalyst with amide-to-alkene peptidomimetic catalyst analogues
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Subtle exchange: Replacement of an amide function with alkene or fluoroalkene groups provides a new class of epoxidation catalysts (see scheme). The structure-dependent catalytic behavior of these isosteric peptides provides mechanistic insights in their mode of action. (Chemical Equation Presented).
- Jakobsche, Charles E.,Peris, Gorka,Miller, Scott J.
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supporting information; experimental part
p. 6707 - 6711
(2009/03/12)
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