- Fusarochromene, a novel tryptophan-derived metabolite from: Fusarium sacchari
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Fusarochromene isolated from the plant pathogenic fungus, Fusarium sacchari is closely related to a group of mycotoxins including fusarochromanone previously isolated from various Fusaria spp. Despite their assumed polyketide biogenesis, incorporation studies with 13C-labelled acetate, glycerol and tryptophans show that fusarochromene is unexpectedly derived via oxidative cleavage of the aromatic amino acid tryptophan. A putative biosynthetic gene cluster has been identified. This journal is
- Marshall, James W.,De Mattos-Shipley, Kate M. J.,Ghannam, Iman A. Y.,Munawar, Asifa,Killen, Jonathan C.,Lazarus, Colin M.,Cox, Russell J.,Willis, Christine L.,Simpson, Thomas J.
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p. 182 - 187
(2021/01/18)
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- Enantioselective Enzymatic Reduction of Acrylic Acids
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An ene-reductase (ERED 36) with broad substrate specificity was identified, and optimization studies led to the development of an enzymatic protocol for the reduction of α,β-unsaturated acids under mild, aqueous conditions. The substrate scope includes aromatic- A nd aliphatic-substituted acrylic acids, as well as cyclic α,β-substituted acrylic acids, yielding chiral α-substituted acids with exquisite levels of enantioselectivity (>99% ee).
- An, Chihui,Shaw, Megan H.,Tharp, Annika,Verma, Deeptak,Li, Hongming,Wang, Heather,Wang, Xiao
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supporting information
p. 8320 - 8325
(2020/11/03)
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- Structure-Enabled Discovery of a Stapled Peptide Inhibitor to Target the Oncogenic Transcriptional Repressor TLE1
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TLE1 is an oncogenic transcriptional co-repressor that exerts its repressive effects through binding of transcription factors. Inhibition of this protein–protein interaction represents a putative cancer target, but no small-molecule inhibitors have been published for this challenging interface. Herein, the structure-enabled design and synthesis of a constrained peptide inhibitor of TLE1 is reported. The design features the introduction of a four-carbon-atom linker into the peptide epitope found in many TLE1 binding partners. A concise synthetic route to a proof-of-concept peptide, cycFWRPW, has been developed. Biophysical testing by isothermal titration calorimetry and thermal shift assays showed that, although the constrained peptide bound potently, it had an approximately five-fold higher Kd than that of the unconstrained peptide. The co-crystal structure suggested that the reduced affinity was likely to be due to a small shift of one side chain, relative to the otherwise well-conserved conformation of the acyclic peptide. This work describes a constrained peptide inhibitor that may serve as the basis for improved inhibitors.
- McGrath, Sally,Tortorici, Marcello,Drouin, Ludovic,Solanki, Savade,Vidler, Lewis,Westwood, Isaac,Gimeson, Peter,Van Montfort, Rob,Hoelder, Swen
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p. 9577 - 9584
(2017/07/22)
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- A Modular Formal Total Synthesis of (±)-Cycloclavine
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Cycloclavine is a clavine-type Ergot alkaloid noteworthy for its unique pentacyclic skeleton featuring a 3-azabicyclo[3.1.0]hexane substructure. A short convergent route to the racemic alkaloid is described which comprises only eight linear steps and requires only four chromatographic purifications. The two key building blocks can be prepared in high yield from commercially available starting materials. Two consecutive coupling reactions, namely a selective alkylation of a dienolate and a Heck reaction, are the key steps of the reaction sequence. (Chemical Equation Presented).
- Netz, Natalie,Opatz, Till
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p. 1723 - 1730
(2016/03/01)
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- Concise synthesis of (2R,4R)-monatin
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Monatin, 4-hydroxy-4-(3-indolylmethyl)-glutamic acid, is a naturally occurring sweet amino acid. The (2R,4R)-monatin isomer has been found to be the sweetest among its four stereoisomers. A concise and efficient synthesis of (2R,4R)-monatin was accomplished by the alkylation of (4R)-N-tert-butoxycarbonyl (tBoc)-4-tert-butyldimethylsilyoxy-D-pyroglutamic acid methyl ester with tert-butyl 3-(bromomethyl)-1H-indole-1-carboxylate to give (4R)-N-tBoc-4-tert-butyldimethylsilyloxy-4-(N-tBoc-3-indolylmethyl)-D-pyroglutamic acid methyl ester, i.e., the lactam form of (2R,4R)-monatin with protecting groups. This was followed by the hydrolysis of the lactam ring and deprotection. The 4-hydroxyl D-pyroglutamic acid derivative was demonstrated to be a suitable precursor for the efficient preparation of (2R,4R)-monatin in high optical purity because the alkylation proceeded in regioselective and stereoselective manners at C4 to form appropriate asymmetric tetra-substituted carbon center; the resulting alkylated pyroglutamic acid derivative was then easily converted into the linear form of monatin.
- Amino, Yusuke
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p. 1242 - 1247
(2016/08/11)
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- Palladium-catalyzed silylation reaction between benzylic halides and silylboronate
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An efficient Pd-catalyzed silylation reaction of benzylic halides with silylboronate is reported. In this reaction, primary and secondary benzylic halides could react well with silylboronates to afford benzylic silanes. This reaction accommodates a broad substrate scope and proceeds smoothly under very mild reaction conditions. The corresponding products could be obtained in moderate to high yields and with stereospecificity.
- Huang, Zhi-Dao,Ding, Ran,Wang, Peng,Xu, Yun-He,Loh, Teck-Peng
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supporting information
p. 5609 - 5612
(2016/05/09)
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- PHENYL-UREA AND PHENYL-CARBAMATE DERIVATIVES AS INHIBITORS OF PROTEIN AGGREGATION
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The present invention relates to certain phenyl-urea and phenyl-carbamate derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, and multiple system atrophy.
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- Synthesis of kurasoin B using phase-transfer-catalyzed acylimidazole alkylation
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The hydroxy ketone natural product kurasoin B is synthesized using a phase-transfer-catalyzed alkylation reaction with benzyloxyacetyl imidazole. A biscinchonidinium dimethylnaphthalene catalyst allowed for high yield and near complete selectivity (99% ee
- Christiansen, Michael A.,Butler, Aaron W.,Hill, Amanda R.,Andrus, Merritt B.
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experimental part
p. 653 - 657
(2009/08/07)
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- Double functionalization of N-Boc-3-(tosylmethyr)indole exploiting the activating properties of the tosyl group
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The anion prepared from N-Boc-3-(tosylmethyl)indole using NaH in DMF can be readily functionalized by reaction with various electrophiles. The obtained sulfonyl indoles, upon removal of the N-protecting group, undergo nucleophilic attack via a vinylogous imino derivative, leading to branched 3-substituted indoles. Georg Thieme Verlag Stuttgart.
- Palmieri, Alessandro,Petrini, Marino,Shaikh, Rafik R.
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scheme or table
p. 1845 - 1851
(2009/04/07)
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- PIPERIDINONES USEFUL IN THE TREATMENT OF INFLAMMATION
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There is provided compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, m and n have meanings given in the description, and pharmaceutically acceptable derivatives thereof, which compounds are useful in the treatment of diseases and conditions associated with inflammation.
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Page/Page column 111
(2008/12/07)
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- Biological activity of the tryprostatins and their diastereomers on human carcinoma cell lines
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Tryprostatin A 1 and B 2 are indole alkaloid-based fungal products that act in the G2/M phase of the cell cycle. Tryprostatin A and B as well as their two enantiomers and four diastereomers have been synthesized via a common strategy. As a measure of cyto
- Zhao, Shuo,Smith, Kirsten S.,Deveau, Amy Morin,Dieckhaus, Christine M.,Johnson, Michael A.,Macdonald, Timothy L.,Cook, James M.
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p. 1559 - 1562
(2007/10/03)
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- Highly diastereoselective alkylation of a pyroglutamate derivative with an electrophile obtained from indole. Synthesis of a potential intermediate for the preparation of the natural sweetener (-)-Monatin
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The synthesis of a potential intermediate for the preparation of the very intensive sweetening agent (-)-Monatin is described. The synthesis is based on a highly diastereoselective alkylation reaction of a pyroglutamate derivative with an electrophile obtained from indole.
- Oliveira, Davi De Jesus,Coelho, Fernando
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p. 2143 - 2159
(2007/10/03)
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- Total synthesis of tryprostatin A and B as well as their enantiomers
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The 3-methylindoles 3a, 3b were convened into tryprostatin A (1a), B (1b) and their enantiomers 2a, 2b via prenylation at the indole 2-position by generation of the required 2-lithioindole derivatives (from 7a, 7b), followed by alkylation.
- Zhao, Shuo,Gan, Tong,Yu, Peng,Cook, James M.
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p. 7009 - 7012
(2007/10/03)
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- Regiospecific Bromination of 3-Methylindoles with NBS and Its Application to the Concise Synthesis of Optically Active Unusual Tryptophans Present in Marine Cyclic Peptides
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A regiospecific bromination of substituted 3-methylindoles at either the C(3) alkyl moiety or the C(2) position was achieved via a free radical bromination or electrophilic process, respectively. The regiospecificity of the bromination could be controlled by variation of both the substituent and the N(1) protecting group on the indole ring. In addition, enantiospecific syntheses of 5-methoxytryptophan (20) and 5-hydroxy-6-chlorotryptophan (21c) as well as concise syntheses of optically active 2-bromotryptophan ethyl esters 26a,b or their substituted derivatives in three steps from bifunctional dibromoindoles were achieved via the above regiospecific process.
- Liu, Ruiyan,Zhang, Puwen,Gan, Tong,Cook, James M.
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p. 7447 - 7456
(2007/10/03)
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- Optimization of 3-(1H-Indazol-3-ylmethyl)-1,5-benzodiazepines as potent, orally active CCK-A agonists
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We previously described a series of 3-(1H-indazol-3-ylmethyl)-1,5- benzodiazepine CCK-A agonists exemplified by compound 1 (GW 5823), which is the first reported binding selective CCK-A full agonist demonstrating oral efficacy in a rat feeding model. In this report we describe analogs of compound 1 designed to explore changes to the CS and N1 pharmacophores and their effect on agonist activity and receptor selectivity. Agonist efficacy in this series was affected by stereoelectronic factors within the C3 moiety. Binding affinity for the CCK-A vs CCK-B receptor showed little dependence on the structure of the C3 moiety but was affected by the nature of the second substituent at CS. Structure-activity relationships at the N1- anilidoacetamide 'trigger' moiety within the C3 indazole series were also investigated. Both agonist efficacy and binding affinity within this series were modulated by variation of substituents on the Nl-anilidoacetamide moiety. Evaluation of several analogs in an in vivo mouse gallbladder emptying assay revealed compound 1 to be the most potent and efficacious of all the analogs tested. The pharmacokinetic and pharmacodynamic profile of 1 in rats is also discussed.
- Henke, Brad R.,Aquino, Christopher J.,Birkemo, Larry S.,Croom, Dallas K.,Dougherty Jr., Robert W.,Ervin, Gregory N.,Grizzle, Mary K.,Hirst, Gavin C.,James, Michael K.,Johnson, Michael F.,Queen, Kennedy L.,Sherrill, Ronald G.,Sugg, Elizabeth E.,Suh, Edward M.,Szewczyk, Jerzy W.,Unwalla, Rayomand J.,Yingling, Jeff,Willson, Timothy M.
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p. 2706 - 2725
(2007/10/03)
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- Catalytic enantioselective synthesis of α-amino acid derivatives by phase-transfer catalysis
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Described are improved processes for the enantioselective synthesis of α-amino acids which involve combinations of solvents, highly-mixed and low-temperature reaction conditions, and novel catalysts. Also described are novel catalysts and precursors to α-amino acid derivatives.
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- A Concise Synthesis of Optically Active 2- Bromotryptophan Amino Acids Present in Konbamide and Jaspamide Via A Regiospecific Bromination Procedure
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A highly stereoselective synthesis of optically active 2-bromo-5-hydroxytryptophan 1a and important derivatives 1b and 1c as well as their 2-bromotryptophan analogs was achieved in three steps from 2-bromo-3-bromomethylindoles 3a and 3b, respectively.
- Zhang, Puwen,Liu, Ruiyan,Cook, James M.
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p. 9133 - 9136
(2007/10/02)
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- Regiospecific bromination of 3-methylindoles with N-bromosuccinimide
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The regiospecific bromination of various substituted 3-methylindoles at either C(2) or the C(3) alkyl moiety was accomplished via an electrophilic of free radical bromination process to provide intermediates for indole alkaloid total synthesis. The regiospecificity of the bromination could be controlled by variation of both the substituent and the N(1) protecting group on the indole ring.
- Zhang, Puwen,Liu, Ruiyan,Cook, James M.
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p. 3103 - 3106
(2007/10/02)
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- Asymmetric Syntheses via Heterocyclic Intermediates, XXIV. - Enantioselective Synthesis of (R)-α-Methyltryptophane Methyl Ester and D-Tryptophane Methyl Ester by the Bislactim Ether Route
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Die Titelverbindungen wurden durch asymmetrische Synthese nach der Bislactimether-Methode hergestellt (e.e. ueber 95percent bzw. etwa 90percent).
- Schoellkopf, Ulrich,Lonsky, Ralph,Lehr, Philipp
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p. 413 - 417
(2007/10/02)
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