- Synthesis of Curvulone B Using the 2-Chlorobenzyl Protecting Group
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A total synthesis of curvulone B has been completed using a Friedel-Crafts reaction and a highly cis-selective intramolecular oxa-Michael addition. The 2-chlorobenzyl protecting group was employed and found to have much greater Lewis acid stability compared to the simple benzyl group.
- Bates, Roderick W.,Wang, Kongchen,Zhou, Guanying,Kang, Dave Zhihong
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p. 751 - 754
(2015/03/30)
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- A facile preparation of α-aryl carboxylic acid via one-flow arndt-eistert synthesis
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An efficient, one-flow Arndt-Eistert synthesis was demonstrated. A sequence of acid chloride formation-nucleophilic acyl substitution-Wolff rearrangement-nucleophilic addition was performed in a microflow system without isolating any intermediates, which
- Fuse, Shinichiro,Otake, Yuma,Mifune, Yuto,Tanaka, Hiroshi
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p. 1657 - 1661
(2015/11/10)
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- Inverting the regioselectivity of the berberine bridge enzyme by employing customized fluorine-containing substrates
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Fluorine is commonly applied in pharmaceuticals to block the degradation of bioactive compounds at a specific site of the molecule. Blocking of the reaction center of the enzyme-catalyzed ring closure of 1,2,3,4- tetrahydrobenzylisoquinolines by a fluoro moiety allowed redirecting the berberine bridge enzyme (BBE)-catalyzed transformation of these compounds to give the formation of an alternative regioisomeric product namely 11-hydroxy-functionalized tetrahydroprotoberberines instead of the commonly formed 9-hydroxy-functionalized products. Alternative strategies to change the regioselectivity of the enzyme, such as protein engineering, were not applicable in this special case due to missing substrate-enzyme interactions. Medium engineering, as another possible strategy, had clear influence on the regioselectivity of the reaction pathway, but did not lead to perfect selectivity. Thus, only substrate tuning by introducing a fluoro moiety at one potential reactive carbon center switched the reaction to the formation of exclusively one regioisomer with perfect enantioselectivity. Custom-made substrates: Employing customized substrates with a fluoro atom at the normally preferred reaction site switched the regioselectivity of the berberine-bridged enzyme. With this strategy, it was possible to get access to (S)-11-hydroxy-functionalized berbines in an asymmetric fashion by using the wild-type enzyme (see scheme). Copyright
- Resch, Verena,Lechner, Horst,Schrittwieser, Joerg H.,Wallner, Silvia,Gruber, Karl,MacHeroux, Peter,Kroutil, Wolfgang
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supporting information
p. 13173 - 13179
(2013/01/15)
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- Characterization of a fungal thioesterase having claisen cyclase and deacetylase activities in melanin biosynthesis
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Melanins are a broad class of darkly pigmented macromolecules formed by oxidative polymerization of phenolic monomers. In fungi, melanins are known virulence factors that contribute to pathogenicity. Their biosynthesis generally involves polymerization of 1,8-dihydroxynaphthalene via a 1,3,6,8- tetrahydroxynaphthalene (THN) precursor assembled by multidomain, nonreducing polyketide synthases. Convergent routes to THN have evolved in fungi. Parallel heptaketide and hexaketide pathways exist that utilize conventional C-terminal thioesterase/Claisen cyclase domains and separate side-chain deacylases. Here, in vitro characterization of Pks1 from Colletotrichum lagenarium establishes a true THN synthase with a bifunctional thioesterase (TE) catalyzing both cyclization and deacetylation of an enzyme-bound hexaketide substrate. Chimeric TE domains were generated by swapping lid regions of active sites between classes of melanin TEs to gain insight into this unprecedented catalysis of carbon-carbon bond making and breaking by an α/β-hydrolase fold enzyme.
- Vagstad, Anna L.,Hill, Eric A.,Labonte, Jason W.,Townsend, Craig A.
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p. 1525 - 1534
(2013/02/25)
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- A diastereoselective formal synthesis of berkelic acid
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A formal synthesis of berkelic acid is reported. The strategy employs the combination of a chiral exocyclic enol ether and an achiral isochromanone to afford the chroman spiroketal core via a base-triggered generation and cycloaddition of an o-quinone met
- Wenderski, Todd A.,Marsini, Maurice A.,Pettus, Thomas R. R.
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supporting information; experimental part
p. 118 - 121
(2011/04/15)
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- 1,3,5 TRI-SUBTITUTED BENZENES FOR TREATMENT OF ALZHEIMER'S DISEASE AND OTHER DISORDERS
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The present disclosure relates to novel 1,3,5 tri-substituted benzenes of general formula (I), (II) or (III) and the use of such compounds in the treatment of diseases associated with the deposition of -amyloid in the brain.
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Page/Page column 93-94
(2009/06/27)
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- PIPERIDINYL AND PIPERAZINYL MODULATORS OF y-SECRETASE
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The present invention relates to compounds of Formula I as shown below, wherein the definitions of Het, R0, R1 R2, R3, R4, R5, R6, R7, R8, and R9 are provided in the specification. Compounds of Formula I are useful for the treatment of diseases associated with γ-secretase activity, including Alzheimer's disease.
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Page/Page column 29
(2009/05/29)
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- CARBON LINKED MODULATORS OF gamma-SECRETASE
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The present invention relates to compounds of Formula I as shown below, wherein the definitions of A, X, R1, R3, R4, R5, R6, R7, R8, and R9 are provided in the specification. Compounds of Formula I are useful for the treatment of diseases associated with γ-secretase activity, including Alzheimer's disease.
- -
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Page/Page column 17
(2009/05/29)
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- AMINE LINKED MODULATORS OF y-SECRETASE
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The present invention relates to compounds of Formula I as shown below, wherein the definitions of A, X, Y, R1 R2, R3, R4, R5, R6, R7, R8, and R9 are provided in the specification. Compounds of Formula I are useful for the treatment of diseases associated with γ-secretase activity, including Alzheimer's disease.
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Page/Page column 23
(2009/05/29)
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- BIPHENYL CARBOXYLIC ACIDS AND DERIVATIVES THEREOF
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The present invention relates to compounds having the general Formula (I) with the definitions of R1, R2, R3, and R4 given below, and/or a salt or ester thereof. Furthermore the invention relates to the use of s
- -
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Page/Page column 9
(2009/05/29)
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- GSM INTERMEDIATES
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The present invention relates the use of compounds having the general Formula I, wherein the definitions or R1 and R2 are provided in the specification. Said compounds of Formula I are useful for the synthesis of a variety of g-secretase modulators, which are in turn useful for the treatment of diseases associated with y-secretase activity, including Alzheimer′s disease.
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Page/Page column 82
(2009/05/28)
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- AMIDE LINKED MODULATORS OF Gamma-SECRETASE
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The present invention relates to compounds of Formula I as shown below, wherein the definitions of A, R1 R2, R3, R4, R5, R6, R7, and R8 are provided in the specification. Compounds of Formula I are useful for the treatment of diseases associated with gamm
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Page/Page column 14
(2009/05/29)
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- Mechanistic studies on the biomimetic reduction of tetrahydroxynaphthalene, a key intermediate in melanin biosynthesis
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1,3,6,8-Tetrahydroxynaphthalene (T4HN) is an aromatic polyketide, serving as a general precursor of fungal melanin. Melanin biosynthesis involves two consecutive deoxygenations of T4HN, consisting of the reduction of a phenolic carbon followed by dehydrat
- Ichinose,Ebizuka,Sankawa
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p. 192 - 196
(2007/10/03)
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- DEOXYGENATION IN THE BIOSYNTHESIS OF POLYKETIDES: MECHANISM OF BIOMIMETIC REDUCTION OF TETRAHYDROXYNAPHTHALENE
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A biomimetic synthesis of scytalone, a simple derivative of tetralone, was reinvestigeted using NMR spectroscopy.Scytalone was formed from 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN) by sodium borohydride reduction only in the presence of sodium methoxi
- Ichinose, Koji,Ebizuka, Yutaka,Sankawa, Ushio
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p. 2873 - 2875
(2007/10/02)
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- Depsidone synthesis. Part 24. The synthesis of epiphorellic acid 2. A pseudo-depsidone and x-ray crystal structure of a grisadienedione epoxide
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The synthesis of the unusual pseudo-depsidone epiphorellic acid 2 (2) {6-hydroxy-3-[5-hydroxy-2-methoxycarbonyl-3-(3-oxopentylphenoxy] -4-methoxy-2-pentylbenzoic acid} by a route involving grisadienedione-depsidone rearrangement and subsequent steps is de
- Comber, Mark F.,Sargent, Melvyn V.,Skelton, Brian W.,White, Allan H.
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p. 441 - 448
(2007/10/02)
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- Drugs derived from Cannabinoids. Part 8. The Synthesis of Side-chain Analogues of Δ6a,10a-Tetrahydrocannabinol
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The continuation of studies on the synthesis of side-chain analogues of Δ6a,10a-tetrahydrocannabinol as potential therapeutic agents has led to the syntheses of a possible metabolite 1-hydroxy-6,6,9-trimethyl-7,8,9,10-tetrahydro-6H-dibenzopyran-3-ylacetic acid (1) and 2-(1-hydroxy-6,6,9-trimethyl-7,8,9,10-tetrahydro-6H-dibenzopyran-3-yl)pent-4-ynoic acid (17c).The Pechmann condensation of ethyl 4-methyl-2-oxocyclohexane-1-carboxylate with methyl 3,5-dihydroxyphenylacetate (11), followed by Grignard reaction, was utilized to produce the pyran (1).The key step in the synthesis of the propargylacetic acid (17c) was propargylation of the malonate (15) under phase-transfer catalysis.
- Meltzer, Peter C.,Dalzell, Haldean C.,Razdan, Raj K.
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p. 2825 - 2829
(2007/10/02)
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- Synthesis of Bikaverin
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The total synthesis of bikaverin (1b) is described, from everninic acid (5) and 3,5-dihydrobenzoic acid (6).Dieckmann condensation of methyl 2-acetyl-3,5-bis(benzyloxy)phenylacetate (14), synthesised from (6), followed by treatment with protected everninic acid chloride (9) gave 1,3-bisbenzyloxy-6,8-bis(2-benzyloxy-4-methoxy-6-methylbenzyloxy)naphthalene (16).Photoinduced Fries rearrangement of (16) afforded 1,3-bis(benzyloxy)-7-(2-benzyloxy-4-methoxy-6-methylbenzoyl)-6-(2-benzyloxy-4-methoxy-6-methylbenzoyloxy)-8-hydroxynaphthalene (23).Ring closure of (23) with tetramethylammonium hydroxide in pyridine gave the angular benzoxanthene, 1,3-bis(benzyloxy-6-hydroxy)-10-methoxy-8-methylbenzoxanthen-7-one (25), which was oxidized with potassium dichromate to give the orthoquinone, 1,3-bis(benzyloxy)-10-methoxy-8-methylbenzoxanthen-5,6,7-trione (28).By a novel type of rearrangement, (28) was transformed into the linear benzoxanthen, 8,10-bis(benzyloxy)-3-methoxy-1-methylbenzoxanthen-6,11,12-trione (29) by treatment with silica gel.Oxidation and debenzylation of (29) with manganese dioxide in concentrated H2SO4 gave norbikaverin (1a).
- Katagiri, Nobuya,Nakano, Jun,Kato, Tetsuzo
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p. 2710 - 2716
(2007/10/02)
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