5053-63-4Relevant academic research and scientific papers
Rapid Access to γ-Amino-α-aryl Alcohol Scaffolds via an Enamine-Based Heck Coupling
Li, Bowen,Tochtrop, Gregory P.
, p. 3851 - 3855 (2022/03/02)
The γ-amino-α-aryl alcohol is a key functional group for the design of inhibitors directed toward a critical family of metabolic enzymes. Here we report the transformation of simple aryl halides to a highly functionalized benzyl (3-oxo-3-arylpropyl)carbamate intermediate that can rapidly be converted to a high value γ-amino-α-aryl alcohol. This chemistry is realized through a two-step process involving an enamine-based Heck coupling (EBHC) followed by a one-pot catalytic Cbz-deprotection and ketone reduction of EBHC products.
Stereoselective Synthesis of C-Vinyl Glycosides via Palladium-Catalyzed C?H Glycosylation of Alkenes
Chen, Gong,He, Gang,Qiao, Tianjiao,Sun, Qikai,Wang, Quanquan,Zhang, Huixing
supporting information, p. 19620 - 19625 (2021/08/09)
C-vinyl glycosides are an important class of carbohydrates and pose a unique synthetic challenge. A new strategy has been developed for stereoselective synthesis of C-vinyl glycosides via Pd-catalyzed directed C?H glycosylation of alkenes with glycosyl chloride donors using an easily removable bidentate auxiliary. Both the γ C?H bond of allylamines and the δ C?H bond of homoallyl amine substrates can be glycosylated in high efficiency and with excellent regio- and stereoselectivity. The resulting C-vinyl glycosides can be further converted to a variety of C-alkyl glycosides with high stereospecificity. These reactions offer a broadly applicable method to streamline the synthesis of complex C-vinyl glycosides from easily accessible starting materials.
Tuning Isonitrile/Tetrazine Chemistry for Accelerated Deprotection and Formation of Stable Conjugates
Xu, Minghao,Deb, Titas,Tu, Julian,Franzini, Raphael M.
, p. 15520 - 15529 (2019/11/29)
The isocyano group is a valuable functionality for bioorthogonal reactions because it rapidly reacts with tetrazines to either form stable conjugates or release payloads from 3-isocyanopropyl groups. Here we provide mechanistic insights into the dissociative steps that follow the initial cycloaddition and analyze how structural modifications affect these processes. Three main outcomes of this study have important implications for designing such groups for bioorthogonal applications. First, anion-stabilizing substituents at C-2 of the 3-isocyanopropyl group promote β-elimination and accelerate deprotection. Second, tetrazines with bulky substituents form stable imine conjugates even with primary isonitriles that are otherwise rapidly hydrolyzed. Third, the elimination step is independent from hydrolysis to the aldehyde and instead can occur directly from the imine intermediate. These findings will allow tuning the structures of tetrazine and isonitrile reactants for application in bioorthogonal ligation and release chemistry.
RAPIDLY RELEASED BIOORTHOGONAL CAGING GROUPS
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Page/Page column 36, (2019/12/25)
Bioorthogonal molecules are disclosed and described. A bioorthogonal a molecule having a structure according to: Formula (I); where R2, R3, and R4 are independently selected from H, a substituted or unsubstituted C1/
HYDROXY ALIPHATIC SUBSTITUTED PHENYL AMINOALKYL ETHER DERIVATIVES
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Paragraph 0363-0364, (2015/12/24)
New hydroxy aliphatic substituted phenyl aminoalkyl ether compounds of formula (I), compositions thereof and their use as a medicament in the treatment of nervous system diseases and/or the treatment of developmental, behavioral and/or mental disorders associated with cognitive deficits.
Total synthesis of fluoxetine and duloxetine through an in situ imine formation/borylation/transimination and reduction approach
Calow, Adam D. J.,Fernandez, Elena,Whiting, Andrew
, p. 6121 - 6127 (2014/08/05)
We report efficient, catalytic, asymmetric total syntheses of both (R)-fluoxetine and (S)-duloxetine from α,β-unsaturated aldehydes conducting five sequential one-pot steps (imine formation/copper mediated β-borylation/transimination/reduction/oxidation) followed by the specific ether group formation which deliver the desired products (R)-fluoxetine in 45% yield (96% ee) and (S)-duloxetine in 47% yield (94% ee). This journal is the Partner Organisations 2014.
Hydroxy aliphatic substituted phenyl aminoalkyl ether derivatives
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Page/Page column, (2014/07/08)
New hydroxy aliphatic substituted phenyl aminoalkyl ether compounds of formula (1), compositions thereof and their use as a medicament in the treatment of nervous system diseases and/or the treatment of developmental, behavioral and/or mental disorders associated with cognitive deficits.
Catalytic asymmetric alkylation reactions for the construction of protected ethylene-amino and propylene-amino motifs attached to quaternary stereocentres
Moss, Thomas A.,Barber, David M.,Kyle, Andrew F.,Dixon, Darren J.
supporting information, p. 3071 - 3081 (2013/03/28)
An efficient catalytic and stereoselective method for the direct construction of protected ethylene-amino and propylene-amino scaffolds attached to quaternary stereocentres is reported. Preliminary investigations revealed a mild base catalysed nucleophilic ring opening of N-sulfonyl aziridines using the commercially available phosphazene base 2-tert-butylimino-2-diethylamino-1,3- dimethyl-perhydro-1,3,2-diazaphosphorine (BEMP) was possible and resulted in highly efficient alkylation reactions with a range of methine carbon acids. This reaction could be rendered highly asymmetric (up to 97 % ee) by employing phase-transfer catalysis to control stereoinduction. Incorporation of alkyl substituents onto the aziridine electrophile, resulted in a highly diastereoselective (up to 30:1 d.r.) variant of this methodology. A further extension using N-protected cyclic sulfamidates as the electrophilic component was successful with a range of pro-nucleophiles (up to 96 % ee and 45:1 d.r.) and allowed a range of nitrogen protecting groups (carbamate, sulfonyl, phosphonyl, benzyl) to be incorporated into the alkylation adducts. Finally, the utility of the products have been demonstrated in the synthesis of useful heterocycles and compounds bearing structural components of natural products. Open sesame: The enantio- and diastereoselective nucleophilic ring opening of protected aziridines and cyclic sulfamidates using asymmetric phase-transfer catalysis (PTC) is reported. The ring-opening alkylation reactions create quaternary chiral centres containing ethylene- and propylene-amino motifs in good yields with good to excellent enantioselectivities (see scheme). These reactions are broad in scope and a wide range of pro-nucleophiles are tolerated. Copyright
Catalytic decarboxylative fluorination for the synthesis of Tri- and difluoromethyl arenes
Mizuta, Satoshi,Stenhagen, Ida S.R.,O'Duill, Miriam,Wolstenhulme, Jamie,Kirjavainen, Anna K.,Forsback, Sarita J.,Tredwell, Matthew,Sandford, Graham,Moore, Peter R.,Huiban, Mickael,Luthra, Sajinder K.,Passchier, Jan,Solin, Olof,Gouverneur, Véronique
supporting information, p. 2648 - 2651 (2013/07/11)
Treatment of readily available α,α-difluoro- and α-fluoroarylacetic acids with Selectfluor under Ag(I) catalysis led to decarboxylative fluorination. This operationally simple reaction gave access to tri- and difluoromethylarenes applying a late-stage fluorination strategy. Translation to [18F]labeling is demonstrated using [ 18F]Selectfluor bis(triflate), a reagent affording [ 18F]tri- and [18F]difluoromethylarenes not within reach with [18F]F2.
PYRAZOLO PYRIMIDINES
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, (2012/07/28)
Compounds of formula and pharmaceutically acceptable salts thereof are described, as well as the pharmaceutical compositions containing said compounds and their pharmaceutically acceptable salts, and the use of said compounds and pharmaceutical compositions for the treatment, control or amelioration of proliferative diseases, including cancer, Down syndrome or early onset Alzheimer's disease.
