295-03-4Relevant academic research and scientific papers
Cytotoxic alkaloids motuporamines A-C: synthesis and structural verification.
Goldring,Weiler
, p. 1471 - 1473 (1999)
[formula: see text] The unusual structure and biological properties of the marine alkaloids motuporamines A-C, as well as the uncertainty as to the position of the olefin within the ring of motuporamine C, led us to synthesize these compounds. The strategy utilized the ring-closing metathesis reaction to form the 14- and 15-membered rings and Michael addition and amidation chemistry to introduce the spermine-like unit. The syntheses, structure assignment verifications, and also the determination of the position of the olefin in motuporamine C are described.
Continuous-Flow Amide and Ester Reductions Using Neat Borane Dimethylsulfide Complex
?tv?s, Sándor B.,Kappe, C. Oliver
, p. 1800 - 1807 (2020/02/27)
Reductions of amides and esters are of critical importance in synthetic chemistry, and there are numerous protocols for executing these transformations employing traditional batch conditions. Notably, strategies based on flow chemistry, especially for amide reductions, are much less explored. Herein, a simple process was developed in which neat borane dimethylsulfide complex (BH3?DMS) was used to reduce various esters and amides under continuous-flow conditions. Taking advantage of the solvent-free nature of the commercially available borane reagent, high substrate concentrations were realized, allowing outstanding productivity and a significant reduction in E-factors. In addition, with carefully optimized short residence times, the corresponding alcohols and amines were obtained in high selectivity and high yields. The synthetic utility of the inexpensive and easily implemented flow protocol was further corroborated by multigram-scale syntheses of pharmaceutically relevant products. Owing to its beneficial features, including low solvent and reducing agent consumption, high selectivity, simplicity, and inherent scalability, the present process demonstrates fewer environmental concerns than most typical batch reductions using metal hydrides as reducing agents.
Nickel-Catalyzed Reduction of Secondary and Tertiary Amides
Simmons, Bryan J.,Hoffmann, Marie,Hwang, Jaeyeon,Jackl, Moritz K.,Garg, Neil K.
supporting information, p. 1910 - 1913 (2017/04/11)
The nickel-catalyzed reduction of secondary and tertiary amides to give amine products is reported. The transformation is tolerant of extensive variation with respect to the amide substrate, proceeds in the presence of esters and epimerizable stereocenters, and can be used to achieve the reduction of lactams. Moreover, this methodology provides a simple tactic for accessing medicinally relevant α-deuterated amines.
N-SUBSTITUTED 3,4-BIS (CATECHOL) PYRROLE COMPOUNDS, AND THE PREPARATION AND USE THEREOF IN THE TREATMENT OF CANCER
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Paragraph 0035; 0036, (2015/12/26)
The present invention relates to a compound of formula (I) in which: —m is an integer from 0 to 3, preferably from 0 to 2; n is an integer from 0 to 3, preferably from 0 to 2; m+n≧1; EAG is an electro-attractive group chosen independently from among a halogen atom, an NO2, CF3, CCI3, CN, CO2H, (C═O)NR2, CH═NR, (C═S)OR, (C═O)SR, CS2R, SO2R, SO2NR2, SO3R, P(O)(OR)2, P(O)(R)2, B(OR)2 group where R is a (C1-C6) alkyl radical, a phenyl group or a hydrogen atom; A is a saturated or unsaturated, linear or branched hydrocarbon chain including 1 to 10 atoms of carbon; and R1 and R2 each represent independently from one another a hydrogen atom, a CO-(Ci-C6)-alkyl, (C1-C6) alkyl, phenyl or phenyl-(C1-C6)-alkyl group, in which R1 and R2 form, together with the nitrogen atom they carry, a 5- to 15-member heterocycle, optionally substituted by a (C1-C6) alkyl group; including its stereoisomers and the mixtures thereof, or a pharmaceutically acceptable salt of same.
A concise formation of N-substituted 3,4-diarylpyrroles-synthesis and cytotoxic activity
Egorov, Maxim,Delpech, Bernard,Aubert, Genevieve,Cresteil, Thierry,Garcia-Alvarez, Maria Concepcion,Collin, Pascal,Marazano, Christian
supporting information, p. 1518 - 1524 (2014/03/21)
A short synthesis of N-substituted 3,4-diarylpyrroles by condensation of a phenacyl halide with a primary amine and a phenylacetaldehyde is reported. The key step is an intramolecular cyclization of an in situ generated enamine onto a ketone. Using differently substituted aromatic reactants and N-(3-aminopropyl)azatricyclodecane as the amine component, the preparation of analogs of the cytotoxic marine alkaloid halitulin could be achieved. The cytotoxicity of some of the compounds obtained by this method was studied, and one of them proved to be a very potent derivative, acting at a nanomolar concentration, in a caspase-independent cell death mechanism.
Tandem conjugate additions and 3-aza-cope rearrangements of tertiary allyl amines and cyclic α-vinylamines with acetylenic sulfones. Applications to simple and iterative ring expansions leading to medium and large-ring nitrogen heterocycles
Weston, Mitchell H.,Nakajima, Katsumasa,Back, Thomas G.
, p. 4630 - 4637 (2008/09/21)
(Chemical Equation Presented) Tertiary acyclic allyl amines and tertiary cyclic α-vinyl amines undergo conjugate additions to acetylenic sulfones to produce zwitterion intermediates, followed by 3-aza-Cope rearrangements. In the case of cyclic α-vinyl amines, the process results in ring-expansion, providing a novel route to 9- to 17-membered cyclic amines. The Hammett plot for the reaction of 8b with 2a-2f shows ρ = +1.19, which is consistent with formation of the proposed zwitterion in the rate-determining step, where electron-withdrawing substituents on the arylsulfonyl moiety stabilize the negative charge and enhance the rate of the reaction. Alternative pathways were observed in methanol in the case of 11, where a methoxy substituent promotes a dissociative mechanism of the corresponding zwitterion via a stabilized allyl cation, whereas the zwitterion derived from amine 12 undergoes ring-opening by direct attack of methanol upon the strained aziridinium moiety instead of by rearrangement. An iterative process was developed, where the product of one ring-expansion is converted into a new cyclic α-vinyl amine, followed by a repetition of the conjugate addition and [3,3] rearrangement. This protocol was illustrated by its application to the synthesis of motuporamine A and B.
Motuporamines, anti-invasion and anti-angiogenic alkaloids from the marine sponge Xestospongia exigua (Kirkpatrick): Isolation, structure elucidation, analogue synthesis, and conformational analysis
Williams, David E.,Craig, Kyle S.,Patrick, Brian,McHardy, Lianne M.,Van Soest, Rob,Roberge, Michel,Andersen, Raymond J.
, p. 245 - 258 (2007/10/03)
Extracts of the sponge Xestospongia exigua collected in Papua New Guinea were positive in a new assay for anti-invasion activity. Bioassay-guided fractionation led to the identification of the three known motuporamines A (1), B (2), and C (3) along with the new motuporamines D (4), E (5), and F (6) and a mixture of G, H, and I (15). Motuporamines A (1), B (2), and C (3) and the mixture of G, H, and I (15) were responsible for the anti-invasion activity of the crude extract. Motuporamine C (3) has also been found to be anti-angiogenic. A series of analogues of the motuporamines have been synthesized and evaluated for anti-invasive activity. These SAR results revealed that a saturated 15-membered cyclic amine fused to the natural motuporamine diamine side chain (13) represented the optimal structure for anti-invasive activity in this family. Single-crystal X-ray diffraction analysis of one of the analogues 20 showed that in the solid state its 16-membered macrocyclic amine fragment adopted the [4444] quadrangular conformation predicted by calculations to be the lowest energy conformation for the corresponding cycloalkane, cyclohexadecane. These data along with literature X-ray data and conformational analysis for derivatives of azacyclotridecane have been used as precedents for predicting the lowest energy ring conformations of other motuporamines. The SAR data from the natural and synthetic motuporamines have been combined with the conformational analyses to provide an outline of the functionality and shape required for activity in this family of alkaloids and to design a new analogue 49 that showed good anti-invasion activity.
Synthesis of medium and large cyclic amines in rhodium-catalysed reactions of aminoalkenes with H2/CO1
Bergmann, David J.,Campi, Eva M.,Roy Jackson,Patti, Antonio F.,Saylik, Dilek
, p. 835 - 844 (2007/10/03)
Rhodium-catalysed reactions of N-benzyl- or N-alkyl-aminoalkenes (6) with H2/CO can give cyclic amines (7) (7-13 ring size) in good to excellent yields when BIPHEPHOS is used as a ligand. Hydrogenation of the aminoalkene becomes a competing reaction for the smaller rings but can be overcome by using a H2/CO gas ratio of 1:5. Reactions of 2-alkenyloxybenzylamines (13) gave 9-, 12- and 17-membered rings (14) in 30-40% yield, but dimer formation (16) and/or hydrogenation were competing reactions. Similar reactions of alkenylamides and ortho-alkenylanilines gave only non-cyclized amino aldehydes as products in low isolated yields.
Total synthesis of cytotoxic sponge alkaloids motuporamines A and B
Baldwin, Jack E.,Vollmer, Heidi R.,Lee, Victor
, p. 5401 - 5404 (2007/10/03)
The synthesis of two sponge alkaloids, Motuporamines A and B is reported. The key step involved a reductive amination using sodium triacetoxyborohydride.
