49851-31-2Relevant articles and documents
Enantioconvergent Cu-Catalyzed Radical C-N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines
Cheng, Jiang-Tao,Dong, Xiao-Yang,Gu, Qiang-Shuai,Li, Zhong-Liang,Liu, Juan,Liu, Xin-Yuan,Luan, Cheng,Wang, Fu-Li,Wang, Li-Lei,Yang, Ning-Yuan,Zhang, Yu-Feng
supporting information, p. 15413 - 15419 (2021/09/30)
α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia and the underdeveloped C(sp3)-N coupling. Here we demonstrate sulfoximines as excellent ammonia surrogates for enantioconvergent radical C-N coupling with diverse racemic secondary alkyl halides (>60 examples) by copper catalysis under mild thermal conditions. The reaction efficiently provides highly enantioenrichedN-alkyl sulfoximines (up to 99% yield and >99% ee) featuring secondary benzyl, propargyl, α-carbonyl alkyl, and α-cyano alkyl stereocenters. In addition, we have converted the masked α-chiral primary amines thus obtained to various synthetic building blocks, ligands, and drugs possessing α-chiral N-functionalities, such as carbamate, carboxylamide, secondary and tertiary amine, and oxazoline, with commonly seen α-substitution patterns. These results shine light on the potential of enantioconvergent radical cross-coupling as a general chiral carbon-heteroatom formation strategy.
NBS-mediated synthesis of β-keto sulfones from benzyl alcohols and sodium arenesulfinates
Muneeswara, Madithedu,Sundaravelu, Nallappan,Sekar, Govindasamy
, p. 3479 - 3484 (2019/05/21)
An efficient synthetic route towards the synthesis of β-keto sulfones has been developed from secondary benzyl alcohols using N-bromosuccinimide (NBS). The present protocol utilizes NBS as oxidant as well as brominating agent, readily accessible benzyl alcohols and sodium arenesulfinates as the sulfonylating reagent under mild conditions. The control experiments revealed that the reaction proceeds via oxidation of alcohol to ketone, α-bromination of ketone and nucleophilic substitution by sodium arenesulfinate. Furthermore, the efficiency of the methodology was tested with a gram scale reaction and also shown the synthetic utility.
Novel benzene-based carbamates for ache/bche inhibition: Synthesis and ligand/structure-oriented sar study
Bak, Andrzej,Kozik, Violetta,Kozakiewicz, Dariusz,Gajcy, Kamila,Strub, Daniel Jan,Swietlicka, Aleksandra,Stepankova, Sarka,Imramovsky, Ales,Polanski, Jaroslaw,Smolinski, Adam,Jampilek, Josef
, (2019/05/10)
A series of new benzene-based derivatives was designed, synthesized and comprehensively characterized. All of the tested compounds were evaluated for their in vitro ability to potentially inhibit the acetyl-and butyrylcholinesterase enzymes. The selectivity index of individual molecules to cholinesterases was also determined. Generally, the inhibitory potency was stronger against butyryl-compared to acetylcholinesterase; however, some of the compounds showed a promising inhibition of both enzymes. In fact, two compounds (23, benzyl ethyl(1-oxo-1-phenylpropan-2-yl)carbamate and 28, benzyl (1-(3-chlorophenyl)-1-oxopropan-2-yl) (methyl)carbamate) had a very high selectivity index, while the second one (28) reached the lowest inhibitory concentration IC50 value, which corresponds quite well with galanthamine. Moreover, comparative receptor-independent and receptor-dependent structure–activity studies were conducted to explain the observed variations in inhibiting the potential of the investigated carbamate series. The principal objective of the ligand-based study was to comparatively analyze the molecular surface to gain insight into the electronic and/or steric factors that govern the ability to inhibit enzyme activities. The spatial distribution of potentially important steric and electrostatic factors was determined using the probability-guided pharmacophore mapping procedure, which is based on the iterative variable elimination method. Additionally, planar and spatial maps of the host–target interactions were created for all of the active compounds and compared with the drug molecules using the docking methodology.
Synthesis of α,β-dibromo ketones by photolysis of α-bromo ketones with N-bromosuccinimide: Photoinduced β-bromination of α-bromo ketones
Moon, Da Yoon,An, Sejin,Park, Bong Ser
, (2019/10/28)
Irradiation of α-bromopropiophenones in the presence of NBS results in the formation of α,β-dibromopropiophenones, which can be viewed as β-bromination of α-bromopropiophenones. The reaction is believed to go through a series of reactions; photoinduced C–Br bond cleavage, elimination of HBr to give α,β-unsaturated ketone intermediates, and addition of Br2, which are formed by the reaction between HBr and NBS. From mechanistic studies of the reaction, we have also found a very convenient method for α-debromination of the α,β-dibromopropiophenones which is by simple irradiation of the dibromo ketones in acetone or 2-propanol without the use of any additives. Our results demonstrate that bromine can be added into or eliminated from the alpha, beta, or both positions to the carbonyl group by photochemical methods, which make synthetic options of bromine containing carbonyl compounds versatile.
Preparation method of alpha-bromo aromatic ketone compounds
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Paragraph 0016, (2018/07/30)
The invention discloses a high-efficiency and green preparation method of alpha-bromo aromatic ketone compounds. The preparation method comprises that under a certain temperature, alpha-H of aromaticketone compounds is brominated to prepare the alpha-bromo aromatic ketone compounds in an acidic medium with hydrogen peroxide as an oxidant and an inorganic bromide as a bromine source under the condition of an alcoholic solvent or solvent-free. The main features of the method are that bromination reagents such as bromine, bromine dioxane, 2,4,4,6-tetrabromocycloketone, perbrominated quaternary ammonium salts, C5H5N.HBr.Br, NBS, dibromohydantoin, copper bromide and cuprous bromide are not used as the bromine source, so that production cost is reduced, and environmental pollution caused by heavy metal bromination reagents is avoided; and in addition, the method uses hydrogen peroxide and inorganic bromide reagents to prepare the alpha-bromo aromatic ketone compounds in situ, the reaction conditions are mild, the experimental operation is simple, the selectivity is good, and the product is single, and therefore, the preparation method has very high applicability and universality, and has a very broad application prospect.
Solvent free, light induced 1,2-bromine shift reaction of α-bromo ketones
An, Sejin,Moon, Da Yoon,Park, Bong Ser
, p. 6922 - 6928 (2018/10/24)
Photolysis of α-bromopropiophenones in acetonitrile results in formation of β-bromopropiophenones with good product selectivity, which can be coined as 1,2-Br shift reaction. The product selectivity increases when the reaction is done in neat or solid state, where only the 1,2-Br shift product is formed in some cases. The reaction is suggested to proceed by C–Br bond homolysis to give a radical pair, followed by disproportionation and conjugate addition of HBr to the α,β-unsaturated ketone intermediate. When the unsaturated intermediate is stabilized by an extra conjugation, the reaction stops at the stage, in which the unsaturated ketone becomes a major product. The synthetic method described in this research fits in a category of eco-friendly organic synthesis nicely since the reaction does not use volatile organic solvents and any other additives such as acid, base or metal catalysts, etc. Besides, the method fits into perfect atom economy, which does not give any side products. The synthetic method should find much advantage over other alternative methods to obtain β-bromo carbonyl compounds.
CERAMIDE GALACTOSYLTRANSFERASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 000388; 000389; 000486; 000487, (2018/01/17)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme ceramide galactosyltransferase (CGT), such as, for example, lysosomal storage diseases. Examples of lysosomal storage diseases include, for example, Krabbe disease and Metachromatic Leukodystrophy.
Catalytic dehydrogenative dual functionalization of ethers: Dealkylation-oxidation-bromination accompanied by C-O bond cleavage: Via aerobic oxidation of bromide
Moriyama, Katsuhiko,Hamada, Tsukasa,Nakamura, Yu,Togo, Hideo
supporting information, p. 6565 - 6568 (2017/07/10)
Catalytic dehydrogenative dual functionalization (DDF) of ethers via oxidation, dealkylation, and α-bromination by the aerobic oxidation of bromide was developed to obtain the corresponding α-bromo ketones in high yields. In particular, the reaction of substituted tetrahydrofurans as cyclic ethers provided 3,3-dibromo tetrahydrofuran-2-ols in high yields selectively through the double α-bromination.
Stereodivergent Synthesis of Chromanones and Flavanones via Intramolecular Benzoin Reaction
Wen, Genfa,Su, Yingpeng,Zhang, Guoxiang,Lin, Qiqiao,Zhu, Yujin,Zhang, Qianqian,Fang, Xinqiang
supporting information, p. 3980 - 3983 (2016/09/09)
The strategy of stereodivergent reactions on racemic mixtures (stereodivergent RRM) was employed for the first time in intramolecular benzoin reactions and led to the rapid access of chromanones/flavanones with two consecutive stereocenters. The easily separable stereoisomers of the products were obtained with moderate to excellent enantioselectivities in a single step. Catechol type additives proved crucial in achieving the desired diastereo- and enantioselectivities.
Copper-catalyzed 1,2-addition of α-carbonyl iodides to alkynes
Xu, Tao,Hu, Xile
supporting information, p. 1307 - 1311 (2015/01/30)
β,γ-Unsaturated ketones are an important class of organic molecules. Herein, copper catalysis has been developed for the synthesis of β-γ-unsaturated ketones through 1,2-addition of α-carbonyl iodides to alkynes. The reactions exhibit wide substrate scope and high functional group tolerance. The reaction products are versatile synthetic intermediates to complex small molecules. The method was applied for the formal synthesis of (±)-trichostatin A, a histone deacetylase inhibitor.
