- Synthesis and structure-activity relationship study of 5a-carbasugar analogues of SL0101
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The Ser/Thr protein kinase, RSK, is associated with oncogenesis, and therefore, there are ongoing efforts to develop RSK inhibitors that are suitable for use in vivo. SL0101 is a natural product that demonstrates selectivity for RSK inhibition. However, SL0101 has a short biological half-life in vivo. To address this issue we designed a set of eight cyclitol analogues, which should be resistant to acid catalyzed anomeric bond hydrolysis. The analogues were synthesized and evaluated for their ability to selectively inhibit RSK in vitro and in cell-based assays. All the analogues were prepared using a stereodivergent palladium-catalyzed glycosylation/cyclitolization for installing the aglycon. The L-cyclitol analogues were found to inhibit RSK2 in in vitro kinase activity with a similar efficacy to that of SL0101, however, the analogues were not specific for RSK in cell-based assays. In contrast, the d-isomers showed no RSK inhibitory activity in in vitro kinase assay. (Chemical Equation Presented).
- Li, Mingzong,Li, Yu,Mrozowski, Roman M.,Sandusky, Zachary M.,Shan, Mingde,Song, Xiwen,Wu, Bulan,Zhang, Qi,Lannigan, Deborah A.,O'Doherty, George A.
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Read Online
- Scalable Asymmetric Synthesis of the All Cis Triamino Cyclohexane Core of BMS-813160
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BMS-813160 is a pharmaceutical entity currently in development at Bristol Myers Squibb. Its defining structural feature is a unique chiral all cis triamino cyclohexane core. Medicinal and process chemistry groups at BMS have previously published synthesis
- La Cruz, Thomas E.,González-Bobes, Francisco,Eastgate, Martin D.,Sfouggatakis, Chris,Zheng, Bin,Kopp, Nathaniel,Xiao, Yi,Fan, Yu,Galindo, Kay A.,Pathirana, Charles,Galella, Michael A.
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p. 1996 - 2011
(2021/09/02)
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- Sustainable Pd(OAc)2/Hydroquinone Cocatalyst System for Cis-Selective Dibenzoyloxylation of 1,3-Cyclohexadiene
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The 1,4-diacyloxylation of 1,3-cyclohexadiene (CHD) affords valuable stereochemically defined scaffolds for natural product and pharmaceutical synthesis. Existing cis-selective diacyloxylation protocols require superstoichiometric quantities of benzoquino
- Borovika, Alina,Eastgate, Martin D.,Fraunhoffer, Kenneth J.,Geng, Peng,Schmidt, Michael A.,Stahl, Shannon S.,Stamoulis, Alexios G.
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supporting information
p. 23182 - 23186
(2021/09/20)
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- Collective Synthesis of Schilancidilactones A, B and Schilancitrilactones A, B, C, 20-epi-Schilancitrilactone A
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Schisandraceae triterpenoids are novel natural products that contain highly fused ring systems bearing multiple chiral centers surrounding. Some of them exhibit promising bioactivities, such as antitumor, anti-HIV, etc. In this article, we describe our ef
- Wang, Hengtao,Wang, Liang,Li, Yihang,Zhang, Xiunan,Tang, Pingping
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p. 255 - 268
(2019/02/16)
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- Total synthesis of schilancitrilactones B and C
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The first total syntheses of schilancitrilactones B and C have been accomplished in 17 steps (longest linear sequence) from commercially available materials. Key steps include an intramolecular radical cyclization to provide the seven-membered ring, late-stage iodination, and an intermolecular radical addition reaction to complete the total synthesis. In step: The first total syntheses of schilancitrilactones B and C have been accomplished by using an intramolecular radical cyclization to provide the seven-membered ring, late-stage iodination, and an intermolecular radical addition reaction as key steps. The approach provides a sequence for the syntheses of compounds related to the schilancitrilactones, as well as their derivatives and analogues.
- Wang, Liang,Wang, Hengtao,Li, Yihang,Tang, Pingping
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supporting information
p. 5732 - 5735
(2015/09/21)
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- Mechanistic insight into the palladium-catalyzed 1,4-oxidation of 1,3-dienes to 1,4-dicarboxy-alk-2-enes
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Side products get involved: The 1,4-oxidation of a diene transforms a simple hydrocarbon into an extremely useful intermediate. A complex formed in situ between palladium and a bicyclic Diels-Alder adduct, which is produced as a side product during the re
- Eastgate, Martin D.,Buono, Frederic G.
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experimental part
p. 5958 - 5961
(2009/12/08)
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- Improved Palladium-Catalyzed 1,4-Haloacyloxylation and 1,4-Diacyloxylation of Cyclic Conjugated Dienes
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Improved procedures for the palladium-catalyzed 1,4-oxidation of cyclic conjugated dienes have been developed.In the new procedures the reactions are performed in acetone or ethyl acetate in the presence of the appropriate carboxylic acid.Thus, palladium-catalyzed oxidations of cyclic conjugated dienes in acetone in the presence of a carboxylic acid and lithium chloride using p-benzoquinone as the oxidant leads to an efficient cis-1,4-chloroacyloxylation.If the reaction is performed in the absence of lithium chloride, but under otherwise identical conditions, a 1,4-diacyloxylation of the conjugated diene takes place. 1,4-Bromoacyloxylation occurs if lithium bromide is used in place of lithium chloride in the palladium-catalyzed oxidation.These new procedures allow the use of a variety of carboxylates in Pd-catalyzed haloacyloxylations and diacyloxylations.
- Baeckvall, Jan-E.,Granberg, Kenneth L.,Hopkins, R. Bruce
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p. 492 - 499
(2007/10/02)
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- STEREOCHEMICAL STUDIES - LVII. SYNTHESIS OF OPTICALLY ACTIVE COMPOUNDS BY THE NOVEL USE OF MESO-COMPOUNDS -1. EFFICIENT SYNTHESIS OF TWO STRUCTURAL TYPES OF OPTICALLY PURE PROSTAGLANDIN INTERMEDIATES.
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With an aim to overcome several inefficient aspects of ordinary methods of preparing optically active compounds, we have developed a new method which recommends utilization of symmetrically functionalized meso-compounds in place of racemic compounds.As shown in Scheme 1, when the meso-compound (I) is monofunctionalized by an optically active functional group (A) and each of the formed diastereomers (II and III) is subjected to further chemical elaborations including protective group transposition, it is theoretically possible to convert the total amount of the starting material (I) into the requisite optically pure product (VI or VII) by selecting synthetic schemes.By employing this novel concept, two structural types of the prostaglandin intermediates ((-)- and (+)-2a,b) have been prepared from the meso-diols (1a,b) by way of the two diastereomeric monoesters (13a,b and 14a,b) which are produced by the reactions 1a,b with N-mesyl- and N-phthaloyl-(S)-phenylalanyl chloride (3a,b).
- Nara, M,Terashima, S.,Yamada, S.
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p. 3161 - 3170
(2007/10/02)
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