13888-01-2Relevant articles and documents
Iridium-Catalyzed Aza-Spirocyclization of Indole-Tethered Amides: An Interrupted Pictet-Spengler Reaction
Gabriel, Pablo,Gregory, Alex W.,Dixon, Darren J.
, p. 6658 - 6662 (2019)
A mild, reductive spirocyclization of indole-linked amides and lactams for the efficient and selective synthesis of aza-spirocyclic indoline products is described. The catalytic reductive activation of tertiary amides or lactams by Vaska's complex with tetramethyldisiloxane as the terminal reductant allowed iminium ion formation, before a diastereoselective 5-endo-trig spirocyclization of the tethered indole moiety was triggered. Terminal reduction affords the aza-spiroindoline products in an overall highly chemoselective and diastereoselective one-pot process.
2 Tyrosine kinase mediated signal transduction inhibitors
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Paragraph 0424; 0425; 0426, (2019/09/17)
Disclosed herein are compounds of Formula (), and pharmaceutically acceptable salts thereof, wherein R, R, R, R, R, X, X, X, X, X, and n are as defined herein, pharmaceutical compositions comprising same, and methods of preparation and use.
Synthesis of Lactones via C-H Functionalization of Nonactivated C(sp3)-H Bonds
Richers, Johannes,Heilmann, Michael,Drees, Markus,Tiefenbacher, Konrad
, p. 6472 - 6475 (2016/12/23)
An electron-deficient amide is utilized as a directing group to functionalize nonactivated C(sp3)-H bonds through radical 1,5-hydrogen abstraction. The γ-bromoamides formed are subsequently converted to γ-lactones under mild conditions. The method described is not limited to tertiary and secondary positions but also allows functionalization of primary nonactivated sp3-hybridized positions in a one-pot sequence. In addition, the broad functional group tolerance renders this method suitable for the late-stage introduction of γ-lactones into complex carbon frameworks.
Lewis Acid Catalyzed Synthesis of α-Trifluoromethyl Esters and Lactones by Electrophilic Trifluoromethylation
Katayev, Dmitry,Matou?ek, Václav,Koller, Raffael,Togni, Antonio
supporting information, p. 5898 - 5901 (2015/12/11)
An electrophilic trifluoromethylation of ketene silyl acetals (KSAs) by hypervalent iodine reagents 1 and 2 has been developed. The reaction proceeds under very mild conditions in the presence of a catalytic amount of trimethylsilyl bis(trifluoromethanesulfonyl)imide (up to 2.5 mol %) as a Lewis acid providing a direct access to a variety of secondary, tertiary, and quaternary α-trifluoromethyl esters and lactones in high yield (up to 98%).
Highly Enantioselective Intermolecular Cu(I)-Catalyzed Cyclopropanation of Cyclic Enol Ethers. Asymmetric Total Synthesis of (+)-Quebrachamine
Temme, Oliver,Taj, Shabbir-Ali,Andersson, Pher G.
, p. 6007 - 6015 (2007/10/03)
A set of cyclic enol ethers derived from 2,3-dihydrofuran 35 and 3,4-dihydropyran 8 with a varying substitution pattern at the olefinic system were synthesized. Evans's ligand 5 with Cu(I)OTf was found to be an effective catalyst in the cyclopropanation reaction between cyclic enol ethers 14, 19, 28-31, and 33 and ethyl diazoacetate 6 to give diastereoselectivities up to exo/endo = 95:5 and enantioselectivities higher than 95% in nearly all cases. Because of the selective building of a quarternary carbon center and good yields in the formation of bicyclic structures 34c-h, the reaction was used as a key step in the asymmetric synthesis of (+)-quebrachamine 7, an indole alkaloid of the Aspidosperma family. After acid-induced ring opening of bicyclic compound 34f to lactone 40 followed by LiAlH4 reduction to the masked aldehyde 41, a reaction with tryptamine gave intermediate 42. This alcohol was efficiently converted into the indole alkaloid (+)-quebrachamine 7 in an overall yield of 37% starting from the chiral synthon 34f. Moreover it revealed the absolute configuration of the quarternary center of the cyclopropanation product 34f to be S.
Synthesis and structure-activity studies of alkyl-substituted γ-butyrolactones and γ-thiobutyrolactones: Ligands for the picrotoxin receptor
Canney,Holland,Levine,McKeon,Ferrendelli,Covey
, p. 1460 - 1467 (2007/10/02)
A series of γ-butyrolactones and γ-thiobutyrolactones possessing a variety of alkyl groups and alkyl-substitution patterns was prepared and evaluated for anticonvulsant and convulsant activity. Behavioral studies performed on these compounds suggest that maximal anticonvulsant activity (against maximal electroshock and pentylenetetrazol) results when three or four carbon atoms are present at the α-position. For convulsant potency, a similar dependence on the size of the alkyl chain at the β-position was observed. Additional γ-dimethyl groups were found to increase the convulsant potency of a β-substituted compound and to cause an an α-substituted anticonvulsant to become a convulsant. In general, sulfur for oxygen heteroatom substitution in the α-substituted lactones resulted in improved anticonvulsant potency and spectrum of activity. Binding of these compounds to the picrotoxin site of the GABA receptor complex was demonstrated with a [35S]-tert-butylbicyclophosphorothionate radioligand binding assay. Measurements of brain concentrations for selected compounds supports a hypothesis that correlates binding to the picrotoxin site with the pharmacological effects of these compounds.
Cyclopropane Derivatives, 3. - (1-Alkylcyclopropyl)ketones by Acylation of α-Substituted γ-Lactones
Boehrer, Gerald,Boehrer, Petra,Knorr, Rudolf
, p. 2167 - 2172 (2007/10/02)
The 2-acylation of 2-substituted 4-butanolides 2 is moderately sensitive to steric crowding, whereas the subsequent ring-opening of 2-acyl-2-alkyl-4-butanolides 4, 11 to give γ-chloroketones 6, 12 by chlorine-transferring acid derivatives becomes difficult with bigger lactone substituents.Similar observations pertain to the preparation of γ-chlorobutanoyl chlorides 10 from 2-alkyl-4-butanolides 2.The proper choice of the starting 4-butanolides (2a, b or 14 but not 2c) provides for an indirect coupling of two different lactones to γ,γ'-dichloro ketones 12.Dicyclopropyl ketones 13 with variable patterns of substitution may thus be prepared from 4-butanolides in a direct manner with global yields exceeding 50percent and without purification of intermediate products (except for acid chlorides like 10).
Synthesis of vinca alkaloids and related compounds, XXXVI A simple synthesis of some D-noreburnamenine derivatives
Kalaus, Gyoergy,Galambos, Janos,Kajtar-Peredy, Maria,Tamas, Jozsef,Szabo, Lajos,et al.
, p. 745 - 750 (2007/10/02)
Reaction of enamine 5 with α-bromoacrylic esters or α-chloroacrylonitrile and subsequent reduction with NaBH4 yielded the pentacyclic D-noreburnamenine derivatives 8-10 or 11-14, respectively.
