1009-89-8Relevant academic research and scientific papers
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 (2002)
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.
Cyclopropenium ion catalysed Beckmann rearrangement
Srivastava, Vishnu P.,Patel, Rajesh,Garima,Yadav, Lal Dhar S.
, p. 5808 - 5810 (2010)
1-Chloro-2,3-diphenylcyclopropenium ion was found to be a very efficient organocatalyst (3 mol% loading) for liquid phase Beckmann rearrangement of various ketoximes to the corresponding amides/lactams within 2 h in acetonitrile at reflux temperature. This is the first example of the application of the cyclopropenium ion as a catalyst, which opens up a new aspect of the synthetic utility of aromatic cation based catalysis.
Synthesis of Cyclic Peptide Mimetics by the Successive Ring Expansion of Lactams
Stephens, Thomas C.,Lodi, Mahendar,Steer, Andrew M.,Lin, Yun,Gill, Matthew T.,Unsworth, William P.
supporting information, p. 13314 - 13318 (2017/10/05)
A successive ring-expansion protocol is reported that enables the controlled insertion of natural and non-natural amino acid fragments into lactams. Amino acids can be installed into macrocycles via an operationally simple and scalable iterative procedure, without the need for high dilution. This method is expected to be of broad utility, especially for the synthesis of medicinally important cyclic peptide mimetics.
Heterolytic (2 e) vs Homolytic (1 e) Oxidation Reactivity: N?H versus C?H Switch in the Oxidation of Lactams by Dioxirans
Annese, Cosimo,D'Accolti, Lucia,Fusco, Caterina,Licini, Giulia,Zonta, Cristiano
supporting information, p. 259 - 262 (2017/01/17)
Dioxiranes are powerful oxidants that can act via two different mechanisms: 1) homolytic (H abstraction and oxygen rebound) and 2) heterolytic (electrophilic oxidation). So far, it has been reported that the nature of the substrate dictates the reaction mode independently from the dioxirane employed. Herein, we report an unprecedented case in which the nature of the dioxirane rules the oxidation chemoselectivity. In particular, a switch from C?H to N?H oxidation is observed in the oxidation of lactams moving from dimethyl dioxirane (DDO) to methyl(trifluoromethyl)dioxirane (TFDO). A physical organic chemistry study, which combines the oxidation with two other dioxiranes methyl(fluoromethyl)dioxirane, MFDO, and methyl(difluoromethyl)dioxirane, DFDO, with computational studies, points to a diverse ability of the dioxiranes to either stabilize the homo or the heterolytic pathway.
Cyanuric chloride as a mild and active Beckmann rearrangement catalyst
Furuya, Yoshiro,Ishihara, Kazuaki,Yamamoto, Hisashi
, p. 11240 - 11241 (2007/10/03)
The first general organocatalytic Beckmann rearrangement of ketoximes into amides has been realized by the catalytic use of cyanuric chloride. Furthermore, acids such as HCl and ZnCl2 are effective as cocatalysts with cyanuric chloride. For example, azacyclotridecan-2-one, which is synthetically useful as a starting material for nylon-12, was prepared in quantitative yield by the Beckmann rearrangement of cyclododecanone oxime (100 mmol scale) catalyzed by cyanuric chloride (0.5 mol %) and ZnCl2 (1 mol %). Copyright
Combination therapy for the treatment of obesity
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, (2008/06/13)
The present invention relates to compositions comprising an appetite suppressant and/or a metabolic rate enhancer and/or a nutrient absorption inhibitor useful for the treatment of obesity, and obesity-related disorders. The present invention further relates to methods of treating or preventing obesity, and obesity-related disorders, in a subject in need thereof by administering a composition of the present invention. The present invention further provides for pharmaceutical compositions, medicaments, and kits useful in carrying out these methods.
Design, synthesis, and biochemical evaluation of N-substituted maleimides as inhibitors of prostaglandin endoperoxide synthases
Kalgutkar, Amit S.,Crews, Brenda C.,Marnett, Lawrence J.
, p. 1692 - 1703 (2007/10/03)
N-(Carboxyalkyl)maleimides are rapid as well as time-dependent inhibitors of prostaglandin endoperoxide synthase (PGHS). The corresponding N- alkylmaleimides were only time-dependent inactivators of PGHS, suggesting that the carboxylate is critical for rapid inhibition. Several N-substituted maleimide analogs containing structural features similar to those of the nonsteroidal anti-inflammatory drug aspirin were synthesized and evaluated as inhibitors of PGHS. Most of the aspirin-like maleimides inactivated the cyclooxygenase activity of purified ovine PGHS-1 in a time- and concentration-dependent manner similar to that of aspirin. The peroxidase activity of PGHS was also inactivated by the maleimide analogs. The cyclooxygenase activity of the inducible isozyme, i.e., PGHS-2, was also inhibited by these compounds. The corresponding succinimide analog of N-5- maleimido-2-acetoxy-1-benzoic acid did not inhibit either enzyme activity, suggesting that inactivation was due to covalent modification of the protein. The mechanism of inhibition of PGHS-1 by N-(carboxyheptyl)maleimide was investigated. Incubation of apoPGHS-1 with 2 equiv of N-(carboxyheptyl)[3,4- 14C]maleimide led to the incorporation of radioactivity in the protein, but no adduct was detected by reversed-phase HPLC, suggesting that it was unstable to the chromatographic conditions. Furthermore, hematin- reconstituted PGHS-1, which was rapidly inhibited by N- (carboxyheptyl)maleimide, displayed spontaneous regeneration of about 50% of the cyclooxygenase and peroxidase activities, suggesting that the adduct responsible for the inhibition breaks down to regenerate active enzyme. ApoPGHS-1, inhibited by N-(carboxyheptyl)maleimide, did not display regeneration of enzyme activity, but addition of hematin to the inhibited apoenzyme led to spontaneous recovery of about 50% of cyclooxygenase activity. These results suggest that addition of heme leads to a conformational change in the protein which increases the susceptibility of the adduct toward hydrolytic cleavage. ApoPGHS-1, pretreated with N(carboxyheptyl)maleimide, was resistant to trypsin cleavage, suggesting that the carboxylate functionality of the maleimide binds in the cyclooxygenase channel. A model for the interaction of N-(carboxyheptyl)maleimide in the cyclooxygenase active site is proposed.
Synthesis of medium ring lactams via cyclization reactions using polymer bound HOBT as catalyst
Huang,Wei, Huang,Kalivretenos,Kalivretenos, Aristotle G.
, p. 9113 - 9116 (2007/10/02)
The synthesis of medium ring lactams (7-, 9-, 11- and 13-membered rings) via cyclization reactions mediated by polymer bound 1-hydroxybenzotriazole (HOBT) is reported.
Method for preparing lactams having 8 to 15 carbon atoms from the corresponding oximes
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, (2008/06/13)
The present invention is a process for preparing lactams having 8 to 15 carbon atoms by the Beckmann rearrangement of the corresponding oximes in a solution of an organic solvent by means of 0.5 to 10% by weight referred to the oxime of an acid derivative acting as a catalyst. The anhydrides of organic sulfonic acids or of sulfuric acid half esters or mixed anhydrides of organic sulfonic acid and anhydrides of sulfuric acid half esters are used as the catalysts.
Aminolysis of N-acyllactams
Stehlicek, Jaroslav,Sebenda, Jan
, p. 2524 - 2531 (2007/10/02)
The overall second-order rate constants of aminolysis of N-benzoyllactams of different ring size, the rate constants of aminolysis of N,N'-isophthaloyl- and N,N'-terephthaloylbis(6-hexanelactam) to the first and second stages and the ratio of splitting of the exocyclic and endocyclic amide bond by octylamine were determined in THF at 50 deg C.The effect of the type of amine and medium on the rate of aminolysis was examined.
