- Cyanopivaloyl Ester in the Automated Solid-Phase Synthesis of Oligorhamnans
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The development of effective protecting group chemistry is an important driving force behind the progress in the synthesis of complex oligosaccharides. Automated solid-phase synthesis is an attractive technique for the rapid assembly of oligosaccharides, built up of repetitive elements. The fact that (harsh) reagents are used in excess in multiple reaction cycles makes this technique extra demanding on the protecting groups used. Here, the synthesis of a set of oligorhamnan fragments is reported using the cyanopivaloyl (PIVCN) ester to ensure effective neighboring group participation during the glycosylation events. The PIVCN group combines the favorable characteristics of the parent pivaloyl (PIV) ester, stability, minimal migratory aptitude, minimal orthoester formation, while it can be cleaved under mild conditions. We show that the remote CN group in the PIVCN renders the PIVCN carbonyl more electropositive and thus susceptible to nucleophilic cleavage. This feature is built upon in the automated solid-phase assembly of the oligorhamnan fragments. Where the use of a PIV-protected building block failed because of incomplete cleavage, PIVCN-protected synthons performed well and allowed the generation of oligorhamnans, up to 16 monosaccharides in length.
- Geert Volbeda, Anne,Van Mechelen, Jeanine,Meeuwenoord, Nico,Overkleeft, Herman S.,Van Der Marel, Gijsbert A.,Codée, Jeroen D. C.
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Read Online
- Hybrids of 4-hydroxy derivatives of goniothalamin and piplartine bearing a diester or a 1,2,3-triazole linker as antiproliferative agents
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A library of nine hybrids of 4-hydroxygoniothalamin (2), 4-hydroxypiplartine (4), monastrol (5) and oxo-monastrol (6) was prepared via a modular synthetic route with a diester or a 1,2,3-triazole as linkers. The compounds were assayed against a panel of h
- Grigolo, Thiago A.,Braga, Carolyne B.,Ornelas, Catia,Russowsky, Dennis,Ferreira-Silva, Guilherme A.,Ionta, Marisa,Pilli, Ronaldo A.
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supporting information
(2021/09/14)
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- THERAPEUTIC AGENTS AND CONJUGATES THEREOF
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The present disclosure provides a class of conjugates of general formula (X), a class of TLR9 agonist derivatives, such as formula (I), (XX), and (XXI), certain diastereomers of STING agonists, a class of STING agonist derivatives, such as formula (XXVIV), a class of heterocyclic compounds of general formula (II), a class of heterocyclic compounds of general formula (III), as defined herein. A1, A2, T, Z1, Z2, Z3, b1, and b2, in formula (X) are defined herein. The conjugate provides unique properties that are based upon the properties of the therapeutic agents that are part of the conjugate. Also provided are methods of synthesis and use of compounds.
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Paragraph 00605-00607
(2021/09/11)
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- Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma
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Many patients with multiple myeloma (MM) initially respond to treatment with modern combination regimens including immunomodulatory agents (lenalidomide and pomalidomide) and proteasome inhibitors. However, some patients lack an initial response to therapy (i.e., are refractory), and although the mean survival of MM patients has more than doubled in recent years, most patients will eventually relapse. To address this need, we explored the potential of novel cereblon E3 ligase modulators (CELMoDs) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). We found that optimization beyond potency of degradation, including degradation efficiency and kinetics, could provide efficacy in a lenalidomide-resistant setting. Guided by both phenotypic and protein degradation data, we describe a series of CELMoDs for the treatment of RRMM, culminating in the discovery of CC-92480, a novel protein degrader and the first CELMoD to enter clinical development that was specifically designed for efficient and rapid protein degradation kinetics.
- Hansen, Joshua D.,Correa, Matthew,Nagy, Mark A.,Alexander, Matt,Plantevin, Veronique,Grant, Virginia,Whitefield, Brandon,Huang, Dehua,Kercher, Timothy,Harris, Roy,Narla, Rama Krishna,Leisten, Jim,Tang, Yang,Moghaddam, Mehran,Ebinger, Katalin,Piccotti, Joseph,Havens, Courtney G.,Cathers, Brian,Carmichael, James,Daniel, Thomas,Vessey, Rupert,Hamann, Lawrence G.,Leftheris, Katerina,Mendy, Derek,Baculi, Frans,Lebrun, Laurie A.,Khambatta, Gody,Lopez-Girona, Antonia
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p. 6648 - 6676
(2020/09/11)
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- Silica-coated Fe3O4 magnetic nanoparticles-supported sulfonic acid as a highly active and reusable catalyst in chemoselective deprotection of tert-butyldimethylsilyl (TBDMS) ethers
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Anchored propyl sulfonic acid on the surface of silica-coated magnetic nanoparticles (Fe3O4@SiO2@PrSO3H) was successfully employed in the deprotection of TBDMS ethers. The prepared magnetically separable nanocatalyst exhibited efficient catalytic activity with high conversion and selectivity in cleavage of TBDMS ethers. TBDMS ethers are efficiently cleaved to the corresponding hydroxyl compounds in methanol solution containing 2 mol% magnetic nano-catalysts. Good to excellent yields of products, simple work-up and product separation, selective cleavage of TBDMS ethers in the presence of TBDPS ethers, easy recycling of the catalyst with external magnet with no loss in its activity (7 reaction cycles) are important features of this new protocol.
- Hossein Javadi, Sayed,Zareyee, Daryoush,Monfared, Azam,Didehban, Khadijeh,Mirshokraee, Sayed Ahmmad
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supporting information
p. 7 - 12
(2019/11/03)
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- CYCLIC-AMP RESPONSE ELEMENT BINDING PROTEIN (CBP) AND/OR ADENOVIRAL E1A BINDING PROTEIN OF 300 KDA (P300) DEGRADATION COMPOUNDS AND METHODS OF USE
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Bivalent compounds composition comprises one or more of the bivalent compounds. The bivalent compound comprises a cyclic-AMP response element binding protein (CBP) and/or adenoviral E1A binding protein of 300kDa (P300) ligand (CBP/P300 ligand) conjugated
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Page/Page column 170
(2020/09/12)
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- Hafnium Triflate as a Highly Potent Catalyst for Regio- and Chemoselective Deprotection of Silyl Ethers
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As a Group IVB transition metal Lewis acid, hafnium triflate [Hf(OTf) 4 ] exhibited exceptionally high potency in desilylations. Since the amounts of Hf(OTf) 4 required for the deprotection of 1°, 2°, 3° alkyl and aryl tert -butyldimethylsilyl (TBS) ethers are significantly different, ranging from 0.05 mol% to 3 mol%, regioselective deprotection of TBS could be easily implemented. Moreover, chemoselective cleavage of different silyl ethers or removal of TBS in the presence of most hydroxyl protecting groups was also accomplished. NMR analyses of silyl products from TBS deprotection indicated that Hf(OTf) 4 -catalyzed desilylation may proceed via different mechanisms, depending on the solvent used.
- Zheng, Xiu-An,Kong, Rui,Huang, Hua-Shan,Wei, Jing-Ying,Chen, Ji-Zong,Gong, Shan-Shan,Sun, Qi
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p. 944 - 953
(2019/02/10)
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- Hafnium trifluoromethanesulfonate catalyzed silyl ether protecting group removing method
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The invention provides a hafnium trifluoromethanesulfonate catalyzed silyl ether protecting group removing method. Various silyl ether protecting groups of nearly 50 kinds of substrates can be efficiently removed in 0.5-16 hours at room temperature by taking 0.02mol%-0.3mol% hafnium trifluoromethanesulfonate as a catalyst, a silyl ether protected hydroxyl compound as a substrate and conventional AR methanol as a solvent. 42 kinds of silyl ether protecting group removing products can be obtained at high yield by performing conventional slica column chromatography purification on a crude product. By regulating the use amount of the catalyst, the Hf(OTf)4 catalyst can realize regioselective removal of 1-degree, 2-degree and 3-degree alkyl TBS and aryl TBS protective groups. Moreover, in a proper equivalent scope, the Hf(OTf)4 catalyst can also realize 1) chemoselective removal of different kinds of silica-based protective groups; and 2) chemoselective removal of 1-degree TBS protective groups under the condition of not affecting a majority of common hydroxyl protective groups.
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Paragraph 0013; 0014
(2019/01/21)
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- Compounds and Their Use in Treating Cancer
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The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts and prodrugs thereof, where R1, R4, R5, R6, R7, Linker, X, Y, A, G, D and E have any of the meanings defined herein. This specification also relates to the use of such compounds and pharmaceutically acceptable salts and prodrugs thereof in methods of treatment of the human or animal body, for example in prevention or treatment of cancer. This specification also relates to processes and intermediate compounds involved in the preparation of such compounds and to pharmaceutical compositions containing them.
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Paragraph 0686; 0687
(2019/07/10)
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- Mild and selective deprotection of tert -butyl(dimethyl)silyl ethers with catalytic amounts of sodium tetrachloroaurate(III) dihydrate
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A simple and mild method for the removal of tert-butyl(dimethyl)silyl (TBS) protecting groups with catalytic amounts of sodium tetrachloroaurate(III) dihydrate is described. The procedure permits selective deprotection of aliphatic TBS ethers in good to excellent yields in the presence of aromatic TBS ethers, aliphatic triisopropylsilyl ethers, aliphatic tert-butyl(diphenyl)silyl ethers, or sterically hindered aliphatic TBS ethers. Additionally, TBS ethers can also be transformed into 4-methoxybenzyl ethers or methyl ethers in one pot by using larger quantities of the catalyst and a higher reaction temperature.
- Zhang, Qi,Kang, Xiuqin,Long, Lei,Zhu, Lijuan,Chai, Yonghai
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- Selective transformations of carbonyl functions in the presence of α,β-unsaturated ketones: Concise asymmetric total synthesis of decytospolides A and B
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Enones selectively react with a combination of PPh3 and TMSOTf to produce phosphonium silyl enol ethers, which work as protective groups of enones during the reduction of other carbonyl functions and can be easily deprotected to regenerate parent enones at workup. Furthermore, the first ketone selective alkylations in the presence of enones were also accomplished. This in situ protection method was applied to concise asymmetric total syntheses of decytospolides A and B.
- Yahata, Kenzo,Minami, Masaki,Watanabe, Kei,Fujioka, Hiromichi
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supporting information
p. 3680 - 3683
(2014/08/05)
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- Palladium-catalyzed direct hydroxymethylation of aryl halides and triflates with potassium acetoxymethyltrifluoroborate
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Suzuki-Miyaura cross-coupling reactions of aryl halides and triflates with potassium acetoxymethyltrifluoroborate afforded the corresponding aryl and heteroaryl methanol products in moderate to excellent yields.
- Murai, Norio,Yonaga, Masahiro,Tanaka, Keigo
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p. 1278 - 1281
(2012/04/23)
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- Peroxisome proliferator-activated receptor agonists with phenethylphenylphthalimide skeleton derived from thalidomide-related liver X receptor antagonists: Relationship between absolute configuration and subtype selectivity
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Introduction of an alkylcarboxylic acid unit, which is a partial structure of endogenous peroxisome proliferator-activated receptor (PPAR) ligands, into a phenethylphenylphthalimide skeleton, which possesses liver X receptor (LXR) antagonistic activity, afforded novel PPAR ligands. The results of structure-activity relationship analysis and docking studies led us to the potent PPAR agonists 13c-e. The absolute configuration of 13c-e affects the PPAR subtype selectivity.
- Motoshima, Kazunori,Ishikawa, Minoru,Hashimoto, Yuichi,Sugita, Kazuyuki
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experimental part
p. 3156 - 3172
(2011/06/26)
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- PIPERAZINE AND AMINOPYRROLIDINE COMPOUNDS AS HISTAMINE H3 RECEPTOR ANTAGONISTS
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The invention relates to compounds of formula (I) wherein R1 to R3 and X0, X1, X2 have the meaning as cited in the description and the claims. Said compounds are useful as Histamine H3 receptor antago
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Page/Page column 48
(2010/12/18)
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- A tetranuclear-zinc-cluster-catalyzed practical and versatile deprotection of acetates and benzoates
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A new catalytic deacylation of acetates and benzoates through transesterification with methanol was developed (see scheme). Reactions with various acidand nucleophile-sensitive functional groups proceeded efficiently in the presence of a catalytic amount of the tetranuclear zinc cluster. The present catalysis is applicable to less-reactive tertiary acetates, the deacylation of which is difficult to achieve by transesterification with other catalysts.
- Iwasaki, Takanori,Agura, Kazushi,Maegawa, Yusuke,Hayashi, Yukiko,Ohshima, Takashi,Mashima, Kazushi
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scheme or table
p. 11567 - 11571
(2010/11/24)
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- Discovery of novel phenethylpyridone derivatives as potent melanin-concentrating hormone 1 receptor antagonists
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Novel phenethylpyridone derivatives were identified as potent human melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. A search for surrogates for the 4-(2-aminoethoxy)phenyl moiety of 1 resulted in discovery of 2-[4-(aminomethyl)phenyl]ethyl substructure as in 6a. Successive optimization of the right-hand moiety led to the identification of a number of potent derivatives.
- Ando, Makoto,Sekino, Etsuko,Haga, Yuji,Moriya, Minoru,Ito, Masahiko,Ito, Junko,Iwaasa, Hisashi,Ishihara, Akane,Kanatani, Akio,Ohtake, Norikazu
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scheme or table
p. 5186 - 5190
(2010/03/24)
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- Deprotection of a silyl group with mesoporous silica
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The triethylsilyl (TES) group of silyl ethers of several types is selectively and easily removed in the presence of a t-butyldimethylsilyl (TBDMS) group with a mesoporous silica MCM-41/MeOH heterogeneous system. Comparison of the efficiency was carried out among several solvents, and among such promoters as common zeolites and ion-exchange resins. Furthermore, FSM-16, another mesoporous silica, was examined for the possibility of recycling by re-calcination at 400°C after the reaction.
- Itoh, Akichika,Kodama, Tomohiro,Masaki, Yukio
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p. 861 - 864
(2008/02/11)
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- Synthesis of heterosubstituted hexaarylbenzenes via asymmetric carbonylative couplings of benzyl halides
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Asymmetric carbonylative couplings of benzyl halldes have been shown to give heterosubstituted 1,3-diarylacetones In moderate to high yields. These asymmetric ketones were converted via Knoevenagel condensations to tetraarylcyclopentadienones, and further
- Potter, Robert G.,Hughes, Thomas S.
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p. 1187 - 1190
(2008/01/04)
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- NOVEL HETEROARYL DERIVATIVE
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A compound of the following formula (1), or its prodrug or pharmaceutically acceptable salt thereof, being useful as a diabetic medicine or preventive, or blood sugar regulator, or therapeutic agent for hyperlipemia, etc. (1) wherein: the ring Z is an optionally substituted heteroaryl, W4 is a single bond, lower alkylene, etc., Ar2 is an optionally substituted aryl, etc., W3 is a single bond, lower alkylene, etc., Ar1 is an optionally substituted arylene, etc., each of W1 and W2 is an optionally substituted lower alkylene, etc., and R1 is carboxyl, an alkoxycarbonyl, etc.
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Page/Page column 96-97
(2008/06/13)
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- Cryptophycin compounds
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The present invention provides cryptophycin compounds of Formula I that are useful in the treatment of neoplasms.
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Page/Page column 150-151
(2010/02/05)
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- Catalytic Conversions in Water. Part 23: Steric Effects and Increased Substrate Scope in the Palladium-Neocuproine Catalyzed Aerobic Oxidation of Alcohols in Aqueous Solvents
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The steric influence of substituents on the 2-and 9-positions of phenanthroline in the (2,9-R2-1,10-phenanthroline)palladium(II)- catalyzed aerobic oxidation of 2-hexanol was investigated by means of high throughput experimentation. (Neocuproine)Pd-(OAc)2 (R=CH 3) was found to be a highly active catalyst for alcohol oxidation in 1:1 water/DMSO mixtures. The catalyst is unique in that it tolerates water, polar co-solvents and a wide variety of functional groups in the alcohol. Turn-over frequencies of > 1500 h-1 were achieved and a series of alcohols was oxidised with 0.1 to 0.5 mol % of catalyst.
- Ten Brink, Gerd-Jan,Arends, Isabel W. C. E.,Hoogenraad, Marcel,Verspui, Goeran,Sheldon, Roger A.
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p. 1341 - 1352
(2007/10/03)
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- Diastereoselective solid-phase radical addition to oxime ether anchored to polymer support
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Stereocontrol in radical reactions of oxime ether anchored to polymer support was studied. Highly diastereoselective solid-phase radical reaction was achieved by using triethylborane and diethylzinc as a radical initiator at low reaction temperature, providing a novel method for the synthesis of the α-amino acid derivatives with excellent diastereoselectivities.
- Miyabe, Hideto,Konishi, Chihiro,Naito, Takeaki
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p. 540 - 544
(2007/10/03)
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- N-benzylpyroglutamyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists
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A series of N-(N-benzylpyroglutamyl)-4-substituted-L-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. Analogues substituted by electron deficient benzoylamino groups bearing bulky ortho substituents had low-nM potency in an ELISA assay an
- Chen, Li,Tilley, Jefferson W.,Guthrie, Robert W.,Mennona, Francis,Huang, Tai-Nan,Kaplan, Gerry,Trilles, Richard,Miklowski, Dorota,Huby, Nicolas,Schwinge, Virginia,Wolitzky, Barry,Rowan, Karen
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p. 729 - 733
(2007/10/03)
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- Stereocontrol in solid-phase radical reactions: Radical addition to oxime ether anchored to polymer support
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(Matrix presented) A high degree of stereocontrol in solid-phase radical reactions was achieved by using triethylborane and diethylzinc as a radical initiator at low reaction temperature. Alkyl radical addition to Oppolzer's camphorsultam derivatives of o
- Miyabe, Hideto,Konishi, Chihiro,Naito, Takeaki
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p. 1443 - 1445
(2007/10/03)
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- Selective deprotection of triethylsilyl group in the presence of t-butyldimethylsilyl group with MCM-41/MeOH heterogeneous system
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Triethylsilyl (TES) group of silyl ethers of several types is selectively and easily removed in the presence of t-butyldimethylsilyl group (TBS) with a mesoporous silica MCM-41/MeOH heterogeneous system. Comparison of the efficiency was carried out among several solvents, and among such promoters as common zeolites and ion-exchange resins. Thieme Stuttgart.
- Itoh, Akichika,Kodama, Tomohiro,Masaki, Yukio
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p. 357 - 359
(2007/10/03)
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- Design, synthesis, derivatization, and structure-activity relationships of simplified, tricyclic, 1,2,4-trioxane alcohol analogues of the antimalarial artemisinin
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Novel C4-(hydroxyalkyl)trioxanes 5d and 5e were designed and synthesized based on an understanding of the molecular mechanism of action of similar 1,2,4-trioxanes structurally related to the antimalarial natural product artemisinin (1). In vitr
- Gumming, Jared N.
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p. 952 - 964
(2007/10/03)
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- Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 2. Design, synthesis, and evaluation of a novel series of phenyl oxazole derivatives
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Synthesis and initial in vitro evaluation of a novel series of phenyl oxazole derivatives are described. An SAR study of the novel dual-acting TRA/TSI agent has revealed that the lipophilicity of the oxazole amide substituents greatly influences the TRA activity but not the TSI. The chain length of the alkenoic acid side chain affects both TRA and TSI. The optimal chain length for the combined activities was found to be n = 4 (heptenoic acid).
- Takeuchi, Kumiko,Kohn, Todd J.,Mais, Dale E.,True, Timothy A.,Wyss, Virginia L.,Jakubowski, Joseph A.
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p. 1943 - 1948
(2007/10/03)
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- (Carboxyalkyl)benzyl propargyl ethers as selective inhibitors of leukocyte-type 12-lipoxygenases
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A series of (carboxyalkyl)benzyl propargyl ethers was synthesized and tested as inhibitors of 12-lipoxygenase (12-LO) from porcine leukocyte cytosol. Optimum activity was displayed by 3-[4-[(2- tridecynyloxy)methyl]phenyl]propanoic acid. Altering the length of the alkyl side chain attached to the acetylenic group reduced activity. Changing the substitution pattern in the (carboxyalkyl)benzyl group from para to meta or ortho also reduced activity. Analogs in which the triple bond was replaced by a double bond or an allene displayed reduced activity, whereas fully saturated analogs were inactive. High concentrations (10 μM) of the most potent acetylenic (carboxylalkyl)benzyl ethers did not inhibit human platelet 12-LO, human neutrophil 5-LO, rabbit reticulocyte 15-LO, or soybean 15-LO. Thus, this class of compounds represents the first example of isoform specific LO inhibitors.
- Gorins, Gilles,Kuhnert, Lethea,Johnson, Carl R.,Marnett, Lawrence J.
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p. 4871 - 4878
(2007/10/03)
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- Selective desilylation of tert-butyldimethylsilyl ethers of phenols using potassium fluoride-alumina and ultrasound
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The use of potassium fluoride on basic alumina in acetonitrile with ultrasound for the selecting deprotection of tert-butyldimethylsilyl ethers of phenols is described. The method, which features a non-aqueous work-up, readily cleaves tert-butyldimethylsilyl ethers of phenols at room temperature, whereas tert-butyldimethylsilyl ethers of benzyl alcohols or 2-(trimethylsilyl) ethoxymethyl ethers of phenols are stable.
- Schmittling, Elisabeth A.,Sawyer, J. Scott
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p. 7207 - 7210
(2007/10/02)
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