108-12-3Relevant academic research and scientific papers
LATEX EXTRACTABLES OF CALOTROPIS GIGANTEA
Thakur, Swapnadip,Das, Prantika,Itoh, Toshihiro,Imai, Kazunori,Matsumoto, Taro
, p. 2085 - 2087 (1984)
The hexane and methanol soluble extract of the latex coagulum of Calotropis gigantea afforded two new triterpene esters, viz. 3'-methylbutanoates of α-amyrin and ψ-taraxasterol, besides the known 3'-methylbutanoates of three triterpene alcohols.The compositions of the alkane fraction, total triterpene alcohol fraction, and free, acetyl and 3'-methylbutanoyl triterpene alcohol fractions of the extract were determined.Key Word Index- Calotropis gigantea; Asclepiadaceae; latex; 3'-methylbutanoyl, acetyl and free α-amyrin, β-amyrin, ψ-taraxasterol, taraxasterol and lupeol; alkanes.
Antiprotozoal glutathione derivatives with flagellar membrane binding activity against T. brucei rhodesiense
Daunes, Sylvie,Yardley, Vanessa,Croft, Simon L.,D'Silva, Claudius
, p. 1329 - 1340 (2017)
A new series of N-substituted S-(2,4-dinitrophenyl)glutathione dibutyl diesters were synthesized to improve in vitro anti-protozoal activity against the pathogenic parasites Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. The results obtained indicate that N-substituents enhance the inhibitory properties of glutathione diesters whilst showing reduced toxicity against KB cells as in the cases of compounds 5, 9, 10, 16, 18 and 19. We suggest that the interaction of N-substituted S-(2,4-dinitrophenyl) glutathione dibutyl diesters with T. b. brucei occurs mainly by weak hydrophobic interactions such as London and van der Waals forces. A QSAR study indicated that the inhibitory activity of the peptide is associated negatively with the average number of C atoms, NCand positively to SZX,the ZX shadow a geometric descriptor related to molecular size and orientation of the compound. HPLC-UV studies in conjunction with optical microscopy indicate that the observed selectivity of inhibition of these compounds against bloodstream form T. b. brucei parasites in comparison to L. donovani under the same conditions is due to intracellular uptake via endocytosis in the flagellar pocket.
Synthesis, pH dependent, plasma and enzymatic stability of bergenin prodrugs for potential use against rheumatoid arthritis
Singh, Rohit,Kumar, Vikas,Bharate, Sonali S.,Vishwakarma, Ram A.
, p. 5513 - 5521 (2017)
Bergenin is a unique C-glycoside natural product possessing anti-inflammatory and anti-arthritic activity. It is hydrophilic molecule and stable under acidic conditions however is unstable at neutral-basic pH conditions. The rate of degradation is directly proportional to the increase in pH which might be one of the reasons for its low oral bioavailability. Thus, herein our objective was to improve its stability using prodrug strategy. Various ester and ether prodrugs were synthesized and studied for lipophilicity, chemical stability and enzymatic hydrolysis in plasma/esterase. The stability of synthesized prodrugs was evaluated in buffers at different pH, in biorelevant media such as SGF, SIF, rat plasma and in esterase enzyme. All prodrugs displayed significantly improved lipophilicity compared with bergenin, which was in accordance with the criteria of drug-like compounds. Acetyl ester 4a2 appeared to be the most promising prodrug as it remained stable at gastric/intestinal pH and was completely transformed to the parent compound bergenin in plasma as desired for an ideal prodrug. The data presented herein, will help in designing stable prodrugs of unstable molecules with desired physicochemical properties in structurally similar chemotypes.
Synthesis of (-)-Indolactam V
Mascal, Mark,Moody, Christopher J.,Slawin, Alexandra M. Z.,Williams, David J.
, p. 823 - 830 (1992)
A stereospecific 7-step synthesis of (-)-indolactam V 1 from tryptophan methyl ester is described.The key steps are the photocyclisation of the dichloroamide 6 to give the isomeric 7-hydroxy-7-isopropylpyrrolobenzazocines 16 + 18 and the nitrene-mediated ring expansion of the derived azide 5 to give the 9-membered imine 4.The synthesis is completed by stereoselective reduction of the imine bond and N-methylation.
Preparative synthesis of vanillin and vanillal alkanoates
Dikusar,Vyglazov,Moiseichuk,Zhukovskaya,Kozlov
, p. 120 - 124 (2005)
Procedures for preparing vanillin and vanillal alkanoates were developed.
A Diverse Library of Chiral Cyclopropane Scaffolds via Chemoenzymatic Assembly and Diversification of Cyclopropyl Ketones
Nam, Donggeon,Steck, Viktoria,Potenzino, Robert J.,Fasan, Rudi
, p. 2221 - 2231 (2021/02/16)
Chiral cyclopropane rings are key pharmacophores in pharmaceuticals and bioactive natural products, making libraries of these building blocks a valuable resource for drug discovery and development campaigns. Here, we report the development of a chemoenzymatic strategy for the stereoselective assembly and structural diversification of cyclopropyl ketones, a highly versatile yet underexploited class of functionalized cyclopropanes. An engineered variant of sperm whale myoglobin is shown to enable the highly diastereo- and enantioselective construction of these molecules via olefin cyclopropanation in the presence of a diazoketone carbene donor reagent. This biocatalyst offers a remarkably broad substrate scope, catalyzing this reaction with high stereoselectivity across a variety of vinylarene substrates as well as a range of different α-aryl and α-alkyl diazoketone derivatives. Chemical transformation of these enzymatic products enables further diversification of these molecules to yield a collection of structurally diverse cyclopropane-containing scaffolds in enantiopure form, including core motifs found in drugs and natural products as well as novel structures. This work illustrates the power of combining abiological biocatalysis with chemoenzymatic synthesis for generating collections of optically active scaffolds of high value for medicinal chemistry and drug discovery.
Design and Synthesis of Natural Product Inspired Libraries Based on the Three-Dimensional (3D) Cedrane Scaffold: Toward the Exploration of 3D Biological Space
Tajabadi, Fatemeh Mazraati,Pouwer, Rebecca H.,Liu, Miaomiao,Dashti, Yousef,Campitelli, Marc R.,Murtaza, Mariyam,Mellick, George D.,Wood, Stephen A.,Jenkins, Ian D.,Quinn, Ronald J.
, p. 6609 - 6628 (2018/07/25)
A chemoinformatic method was developed to extract nonflat scaffolds embedded in natural products within the Dictionary of Natural Products (DNP). The cedrane scaffold was then chosen as an example of a nonflat scaffold that directs substituents in three-dimensional (3D) space. A cedrane scaffold that has three orthogonal handles to allow generation of 1D, 2D, and 3D libraries was synthesized on a large scale. These libraries would cover more than 50% of the natural diversity of natural products with an embedded cedrane scaffold. Synthesis of three focused natural product-like libraries based on the 3D cedrane scaffold was achieved. A phenotypic assay was used to test the biological profile of synthesized compounds against normal and Parkinson's patient-derived cells. The cytological profiles of the synthesized analogues based on the cedrane scaffold revealed that this 3D scaffold, prevalidated by nature, can interact with biological systems as it displayed various effects against normal and Parkinson's patient-derived cell lines.
Photoinduced, Copper-Catalyzed Decarboxylative C-N Coupling to Generate Protected Amines: An Alternative to the Curtius Rearrangement
Zhao, Wei,Wurz, Ryan P.,Peters, Jonas C.,Fu, Gregory C.
supporting information, p. 12153 - 12156 (2017/09/12)
The Curtius rearrangement is a classic, powerful method for converting carboxylic acids into protected amines, but its widespread use is impeded by safety issues (the need to handle azides). We have developed an alternative to the Curtius rearrangement that employs a copper catalyst in combination with blue-LED irradiation to achieve the decarboxylative coupling of aliphatic carboxylic acid derivatives (specifically, readily available N-hydroxyphthalimide esters) to afford protected amines under mild conditions. This C-N bond-forming process is compatible with a wide array of functional groups, including an alcohol, aldehyde, epoxide, indole, nitroalkane, and sulfide. Control reactions and mechanistic studies are consistent with the hypothesis that copper species are engaged in both the photochemistry and the key bond-forming step, which occurs through out-of-cage coupling of an alkyl radical.
NOVEL COMPOSITIONS, USES AND METHODS FOR THEIR PREPARATION
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Paragraph 0271; 0272, (2015/05/05)
The present invention relates to novel compunds and pharmaceutical compositions thereof which may be useful in the treatment and/or prevention of various conditions. The present invention also provides methods of prearing such compounds and compositions, and methods of using the same.
BENZOPIPERAZINE COMPOSITIONS AS BET BROMODOMAIN INHIBITORS
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Paragraph 00407, (2015/06/03)
The present invention relates to inhibitors of bromo and extra terminal (BET) bromodomains that are useful for the treatment of cancer, inflammatory diseases, diabetes, and obesity, having Formula (I): wherein X, Y, Z, R1, R2, R4 and R7 are defined herein.
