2111-53-7Relevant academic research and scientific papers
29. Total synthesis of crenulatan diterpenes: Strategy and stereocontrolled construction of a bicyclic keto-lactone building block
He,Pinard,Paquette
, p. 391 - 402 (1995)
The bicyclic keto lactone 26 was synthesized for the purpose of developing a viable route to marine diterpenes of the crenulatan type. Following the efficient conversion of (S)-citronellol (5) to the allylated alcohol 9a, the α,β -unsaturated lactone 12 was efficiently accessed in preparation for stereocontrolled conjugate addition. The hydroxymethyl equivalent most suited to this task was (i-PrO)Me2SiCH2MgCl, which gave 13 predominantly in the presence of CuI and Me3SiCl. Once the OH group was deprotected (→14), it proved an easy matter to implement acid-catalyzed isomerization to lactone 15, oxidation of which gave the pivotal aldehyde 16. Condensation of 16 with PhSeCH2Li led via 21 to 22. Once the OH group was protected (→22b), it proved possible to effect aldolization with crotonaldehyde (→23). Exposure of 23 to acid gave the sub-target compound 25. Its subsequent oxidation and thermal activation resulted in sequential selenoxide elimination with Claisen rearrangement (→26). The structural features of 26 require that a chair-like transition state be adopted during the [3.3]sigmatropic event. With the clarification of these issues, a highly serviceable and more advanced assault on the crenulatans should prove capable of being mounted.
Stereospecificity of Pig Kidney and Pea Seedling Diamino Oxidases on 2-Methyl-1,4-diaminobutane
Santaniello, Enzo,Manzocchi, Ada,Biondi, Pier Antonio,Secchi, Camillo,Simonic, Tatijana
, p. 803 - 804 (1984)
Diamine oxidase from pea seedlings (PDAO) oxidizes both (R)- and (S)-2-methylputrescine at the less hindered C-4, whereas pig-kidney diamine oxidase (KDAO) shows a dependence on the stereochemistry of the substrate, since the (R)-isomer is oxidized at C-1 and the (S)-isomer at the less hindered amino group at C-4.
Oxidation of Primary Alcohols and Aldehydes to Carboxylic Acids via Hydrogen Atom Transfer
Tan, Wen-Yun,Lu, Yi,Zhao, Jing-Feng,Chen, Wen,Zhang, Hongbin
supporting information, p. 6648 - 6653 (2021/09/08)
The oxidation of primary alcohols and aldehydes to the corresponding carboxylic acids is a fundamental reaction in organic synthesis. In this paper, we report a new chemoselective process for the oxidation of primary alcohols and aldehydes. This metal-free reaction features a new oxidant, an easy to handle procedure, high isolated yields, and good to excellent functional group tolerance even in the presence of vulnerable secondary alcohols and tert-butanesulfinamides.
Modulation of the Passive Permeability of Semipeptidic Macrocycles: N- And C-Methylations Fine-Tune Conformation and Properties
Boudreault, Pierre-Luc,Comeau, Christian,Derbali, Rabeb Mouna,Grandbois, Michel,Poulet, Sylvain,Ries, Benjamin,Riniker, Sereina,Sarret, Philippe,Stadelmann, Thomas,Tremblay, Jacob,C?té, Jér?me,Fr?hlich, Ulrike,Leclair, Grégoire,Marsault, éric
, p. 5365 - 5383 (2021/05/04)
Incorporating small modifications to peptidic macrocycles can have a major influence on their properties. For instance, N-methylation has been shown to impact permeability. A better understanding of the relationship between permeability and structure is of key importance as peptidic drugs are often associated with unfavorable pharmacokinetic profiles. Starting from a semipeptidic macrocycle backbone composed of a tripeptide tethered head-to-tail with an alkyl linker, we investigated two small changes: peptide-to-peptoid substitution and various methyl placements on the nonpeptidic linker. Implementing these changes in parallel, we created a collection of 36 compounds. Their permeability was then assessed in parallel artificial membrane permeability assay (PAMPA) and Caco-2 assays. Our results show a systematic improvement in permeability associated with one peptoid position in the cycle, while the influence of methyl substitution varies on a case-by-case basis. Using a combination of molecular dynamics simulations and NMR measurements, we offer hypotheses to explain such behavior.
Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors
Goetz, Daniel B.,Holstein, Sarah A.,Varney, Michelle L.,Wiemer, David F.
, (2020/07/10)
Geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma. A series of bisphosphonates linked to an isoprenoid tail through an amide linkage has been prepared and tested for the ability to inhibit GGDPS in enzyme and cell-based assays. The amides were designed as analogues to triazole-based GGDPS inhibitors. Several of the new compounds show GGDPS inhibitory activity in both enzyme and cell assays, with potency dependent on chain length and olefin stereochemistry.
PPAR AGONISTS, COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
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Page/Page column 104-105, (2017/04/23)
Provided herein are compounds and compositions useful in increasing PPAR8 activity. The compounds and compositions provided herein are useful for the treatment of PPAR8 related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).
A general approach to iridoids by applying a new Julia olefination and a tandem anion-radical-carbocation crossover reaction
?ehová, Lucie,Dra?ínsky, Martin,Jahn, Ullrich
supporting information, p. 9612 - 9621 (2016/10/22)
A unified, asymmetric approach to the total synthesis of naturally occurring iridoids is presented. The synthesis features a recently discovered ortho → α transmetalation of alkyl aryl sulfone carbanions, thus enabling Julia reactions, by which so far har
Rational Development of a Potent 15-Lipoxygenase-1 Inhibitor with in Vitro and ex Vivo Anti-inflammatory Properties
Eleftheriadis, Nikolaos,Neochoritis, Constantinos G.,Leus, Niek G. J.,Van Der Wouden, Petra E.,D?mling, Alexander,Dekker, Frank J.
, p. 7850 - 7862 (2015/10/20)
Human 15-lipoxygenase-1 (h-15-LOX-1) is a mammalian lipoxygenase and plays an important role in several inflammatory lung diseases such as asthma, COPD, and chronic bronchitis. Novel potent inhibitors of h-15-LOX-1 are required to explore the role of this enzyme further and to enable drug discovery efforts. In this study, we applied an approach in which we screened a fragment collection that is focused on a diverse substitution pattern of nitrogen-containing heterocycles such as indoles, quinolones, pyrazoles, and others. We denoted this approach substitution-oriented fragment screening (SOS) because it focuses on the identification of novel substitution patterns rather than on novel scaffolds. This approach enabled the identification of hits with good potency and clear structure-activity relationships (SAR) for h-1-5-LOX-1 inhibition. Molecular modeling enabled the rationalization of the observed SAR and supported structure-based design for further optimization to obtain inhibitor 14d that binds with a Ki of 36 nM to the enzyme. In vitro and ex vivo biological evaluations of our best inhibitor demonstrate a significant increase of interleukin-10 (IL-10) gene expression, which indicates its anti-inflammatory properties.
Straightforward synthesis of functionalized (E)-3-acylacrylic acids
Sivák, Ivan,Václav, Jakub,Berke?, Du?an,Kolarovi?, Andrej
supporting information, p. 8871 - 8875 (2015/11/02)
An experimentally simple, mild and straightforward synthetic route towards diversely functionalized (E)-3-acylacrylic acids is described, with Horner-Wadsworth-Emmons (HWE) reaction as the key step. The substrate scope and limitations of the HWE reaction were investigated with a range of β-ketophosphonates. Glyoxylic acid monohydrate was demonstrated to be fully compatible with the HWE reaction conditions, thus avoiding a troublesome hydrolysis of the corresponding 3-acylacrylates in the last step and providing a valuable synthetic shortcut.
Enantioselective rearrangement coupled with water addition: Direct synthesis of enantiomerically pure saturated carboxylic acids from α,β-unsaturated aldehydes
Winkler, Till,Groeger, Harald,Hummel, Werner
, p. 961 - 964 (2014/05/06)
A novel type of organic synthesis enabling a direct one-pot transformation of α,β-unsaturated aldehydes into saturated carboxylic acids is described. As sole reagent water is required, which is integrated completely in the product. This tandem process proceeds under perfect atom economy, and consists of two coupled redox biotransformations without the need of external co-substrates for cofactor regeneration. The initial reduction of the C=C double bond of an α,β-unsaturated aldehyde is catalyzed by an NADPH-dependent ene reductase, leading to the formation of the saturated aldehyde and NADP+. The aldehyde intermediate is then oxidized to the corresponding carboxylic acid, thus regenerating NADPH for the next catalytic cycle. When using prochiral α,β-unsaturated aldehydes as substrates the corresponding carboxylic acids are formed enantioselectively with up to >99 % ee as demonstrated, e.g., for the transformation of citral to (S)-citronellic acid. Making a splash with citral: The direct one-pot transformation of α,β-unsaturated aldehydes to saturated carboxylic acids using only water proceeds with perfect atom economy. This tandem process involves two redox biotransformations without need of additional external co-substrates for cofactor regeneration. With, for example, citral as prochiral α,β-unsaturated aldehyde, transformation to (S)-citronellic acid proceeds with >99 % conversion and >99 % ee.
