593-47-5Relevant academic research and scientific papers
Balancing the efficacy vs. the toxicity of promiscuous natural products: Paclitaxel-based acid-labile lipophilic prodrugs as promising chemotherapeutics
Chittiboyina, Amar G.,Claudio, Pier Paolo,Haider, Saqlain,McChesney, James D.,Penfornis, Patrice
, (2021/10/19)
TumorSelect is an anticancer technology that combines cytotoxics, nanotechnology, and knowledge of human physiology to develop innovative therapeutic interventions with minimal undesirable side effects commonly observed in conventional chemotherapy. Tumors have a voracious appetite for cholesterol which facilitates tumor growth and fuels their proliferation. We have transformed this need into a stealth delivery system to disguise and deliver anticancer drugs with the assistance of both the human body and the tumor cell. Several designer prodrugs are incorporated within pseudo-LDL nanoparticles, which carry them to tumor tissues, are taken up, internalized, transformed into active drugs, and inhibit cancer cell proliferation. Highly lipophilic prodrug conjugates of paclitaxel suitable for incorporation into the pseudo-LDL nanoparticles of the TumorSelect delivery vehicle formulation were designed, synthesized, and evaluated in the panel of 24-h NCI-60 human tumor cell line screening to demonstrate the power of such an innovative approach. Taxane prodrugs, viz., ART-207 was synthesized by tethering paclitaxel to lipid moiety with the aid of a racemic solketal as a linker in cost-effective, simple, and straightforward synthetic transformations. In addition to the typical 24-h NCI screening protocol, these compounds were assessed for growth inhibition or killing of ovarian cell lines for 48 and 72h-time intervals and identified the long-lasting effectiveness of these lipophilic prodrugs. All possible, enantiomerically pure isomers of ART-207 were also synthesized, and cytotoxicities were biosimilar to racemic ART-207, suggesting that enantiopurity of linker has a negligible effect on cell proliferation. To substantiate further, ART-207 was evaluated for its in vivo tumor reduction efficacy by studying the xenograft model of ovarian cancer grown in SCID mice. Reduced weight loss (a measure of toxicity) in the ART-207 group was observed, even though it was dosed at 2.5x the paclitaxel equivalent of Abraxane. As a result, our delineated approach is anticipated to improve patient quality of life, patient retention in treatment regimes, post-treatment rapid recovery, and overall patient compliance without compromising the efficacy of the cytotoxic promiscuous natural products.
SYNTHESIS OF PHEROMONE DERIVATIVES VIA Z-SELECTIVE OLEFIN METATHESIS
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Paragraph 0218, (2021/12/28)
Disclosed herein are methods for synthesizing fatty olefin metathesis products of high Z-isomeric purity from olefin feedstocks of low Z-isomeric purity. The methods include contacting a contacting an olefin metathesis reaction partner, such as acylated alkenol or an alkenal acetal, with an internal olefin in the presence of a Z-selective metathesis catalyst to form the fatty olefin metathesis product. In various embodiments, the fatty olefin metathesis products are insect pheromones. Pheromone compositions and methods of using them are also described.
OLEIC ACID DERIVATIVES AS TREATMENTS FOR FRIEDREICH ATAXIA AND INHIBITORS OF FERROPTOSIS
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, (2021/05/21)
The invention relates to compounds of Formula I or Formula II: to compositions comprising such compounds, and to methods of use thereof for treating neurdegenerative disorders, such as Friedreich ataxia.
A Facile and Efficient Method for the Synthesis of Labeled and Unlabeled Very Long Chain Polyunsaturated Fatty Acids
Hamberg, Mats
, p. 489 - 494 (2021/04/19)
Several methods are available for elongation of fatty acid acyl chains. The present paper describes adaptation to the fatty acid field of a previously published protocol for manganese-based Wurtz type coupling of alkyl bromides. 22-Bromo-3(Z),6(Z),9(Z),12(Z),15(Z),18(Z)-docosahexaene, easily prepared from 4(Z),7(Z),10(Z),13(Z),16(Z),19(Z)-docosahexaenoic acid, was coupled to homologous ω-bromoesters by stirring for 4 hours at 40°C in the presence of manganese powder, a nickel catalyst and terpyridine. This afforded in yields of 70–75% a series of ω3-hexaenoates of chain lengths of 32–40 carbons. The corresponding fatty acids of >98% purity were obtained following saponification and final purification. By using methyl [2,2,3,3,4,4-2H6]10-bromodecanoate as coupling partner it was possible to prepare a very long chain fatty acid in isotopically labeled form, i.e., [2,2,3,3,4,4-2H6]14(Z),17(Z),20(Z),23(Z),26(Z),29(Z)-dotriacontahexaenoic acid. Also prepared were the monounsaturated long chain fatty acids 15(Z)-octadecenoic acid and 15(Z)-tetracosenoic acid. Very long chain fatty acids have been isolated from retina and other tissues and are of biological relevance. The methodology described will assist in further analytical and biological studies in this field.
Enantiomeric synthesis of natural alkylglycerols and their antibacterial and antibiofilm activities
Fernández Montoya, Deicy J.,Contreras Jordan, Luis A.,Moreno-Murillo, Bárbara,Silva-Gómez, Edelberto,Mayorga-Wandurraga, Humberto
supporting information, p. 2544 - 2550 (2019/11/13)
Alkylglycerols (AKGs) are bioactive natural compounds that vary by alkyl chain length and degree of unsaturation, and their absolute configuration is 2S. Three AKGs (5l–5n) were synthesised in enantiomerically pure form, and were characterised for the first time together with 12 other known and naturally occurring AKGs (5a–5k, 5o). Their structures were established using 1H and 13C APT NMR with 2D-NMR, ESI-MS or HRESI-MS and optical rotation data, and they were tested for their antibacterial and antibiofilm activities. AKGs 5a–5m and 5o showed activity against five clinical isolates and P. aeruginosa ATCC 15442, with MIC values in the range of 15–125 μg/mL. In addition, at half of the MIC, most of the AKGs reduced S. aureus biofilm formation in the range of 23%–99% and P. aeruginosa ATCC 15442 biofilm formation in the range of 14%–64%. The antibiofilm activity of the AKGs assessed in this work had not previously been studied.
Hydrosilylation of Esters Catalyzed by Bisphosphine Manganese(I) Complex: Selective Transformation of Esters to Alcohols
Bagh, Bidraha,Behera, Rakesh R.,Ghosh, Rahul,Khamari, Subrat,Panda, Surajit
supporting information, p. 3642 - 3648 (2020/04/20)
Selective and efficient hydrosilylations of esters to alcohols by a well-defined manganese(I) complex with a commercially available bisphosphine ligand are described. These reactions are easy alternatives for stoichiometric hydride reduction or hydrogenation, and employing cheap, abundant, and nonprecious metal is attractive. The hydrosilylations were performed at 100 °C under solvent-free conditions with low catalyst loading. A large variety of aromatic, aliphatic, and cyclic esters bearing different functional groups were selectively converted into the corresponding alcohols in good yields.
Design and synthesis of amphiphilic 2-hydroxybenzylphosphonium salts with antimicrobial and antitumor dual action
Lyubina, Anna P.,Mironov, Vladimir F.,Pashirova, Tatiana N.,Sapunova, Anastasiia S.,Shaihutdinova, Zukhra M.,Tatarinov, Dmitry A.,Terekhova, Natalia V.,Voloshina, Alexandra D.,Zakharova, Lucia Ya.
supporting information, (2020/05/19)
Here we report the synthesis and biological evaluation of a series of new 2-hydroxybenzylphosphonium salts (QPS) with antimicrobial and antitumor dual action. The most active compounds exhibit antimicrobial activity at a micromolar level against Gram-positive bacteria Sa (ATCC 209p and clinical isolates), Bc (1–2 μM) and fungi Tm and Ca, and induced no notable hemolysis at MIC. The change in nature of substituents of the same length led to a drastic change of biological activity. Self-assembly behavior of the octadecyl and oleyl derivatives was studied. QPS demonstrated self-assembly within the micromolar range with the formation of nanosized aggregates capable of the solubilizing hydrophobic probe. The synthesized phosphonium salts were tested for cytotoxicity. The most potent salt was active against on M?Hela cell line with IC50 on the level of doxorubicin and good selectivity. According to the cytofluorimetry analysis, the salts induced mitochondria-dependent apoptosis.
Manganese-catalysed transfer hydrogenation of esters
Oates, Conor L.,Widegren, Magnus B.,Clarke, Matthew L.
supporting information, p. 8635 - 8638 (2020/08/21)
Manganese catalysed ester reduction using ethanol as a hydrogen transfer agent in place of dihydrogen is reported. High yields can be achieved for a range of substrates using 1 mol% of a Mn(i) catalyst, with an alkoxide promoter. The catalyst is derived from a tridentate P,N,N ligand.
Diaminodiphosphine tetradentate ligand and ruthenium complex thereof, and preparation methods and applications of ligand and complex
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Paragraph 0307-0310, (2019/11/04)
The invention discloses a diaminodiphosphine tetradentate ligand and a ruthenium complex thereof, and preparation methods and applications of the ligand and the complex, and provides a ruthenium complex represented by a formula I, wherein L is a diaminodiphosphine tetradentate ligand represented by a formula II, and X and Y are respectively and independently chlorine ion, bromine ion, iodine ion,hydrogen negative ion or BH4. According to the present invention, the ruthenium complex exhibits excellent catalytic activity in the catalytic hydrogenation reactions of ester compounds, has high yield and high chemical selectivity, is compatible with conjugated and non-conjugated carbon-carbon double bond, carbon-carbon triple bond, epoxy, halogen, carbonyl and other functional groups, and hasgreat application prospects.
Novel clamp metal complex and application thereof
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Paragraph 0410-0412; 0450-0453; 0519-0522, (2019/04/26)
The invention discloses a method for preparing a novel clamp-shaped complex and application of the novel clamp-shaped complex in the reaction of catalytic hydrogenation of carboxylic acid ester compounds to produce corresponding alcohols and reaction of carbon dioxide catalytic hydrogenation to form formamide compounds. Carboxylic acid esters and hydrogen as raw materials or carbon dioxide, hydrogen and amine compounds as raw materials are reacted in an organic solvent condition or a solvent-free condition in the presence of a transition metal complex as a catalyst to respectively form the corresponding alcohol compounds and/or corresponding formamide compounds. The method has the advantages of being high in reaction efficiency, good in selectivity, mild in conditions, economical, environmentally-friendly, and simple in operation, and has good promotion and application prospects.
