111425-86-6Relevant academic research and scientific papers
Development of isotope-enriched phosphatidylinositol-4- And 5-phosphate cellular mass spectrometry probes
Joffrin, Amélie M.,Saunders, Alex M.,Barneda, David,Flemington, Vikki,Thompson, Amber L.,Sanganee, Hitesh J.,Conway, Stuart J.
, p. 2549 - 2557 (2021/03/01)
Synthetic phosphatidylinositol phosphate (PtdInsPn) derivatives play a pivotal role in broadening our understanding of PtdInsPnmetabolism. However, the development of such tools is reliant on efficient enantioselective and regioselective synthetic strategies. Here we report the development of a divergent synthetic route applicable to the synthesis of deuterated PtdIns4Pand PtdIns5Pderivatives. The synthetic strategy developed involves a key enzymatic desymmetrisation step using Lipozyme TL-IM. In addition, we optimised the large-scale synthesis of deuteratedmyo-inositol, allowing for the preparation of a series of saturated and unsaturated deuterated PtdIns4Pand PtdIns5Pderivatives. Experiments in MCF7 cells demonstrated that these deuterated probes enable quantification of the corresponding endogenous phospholipids in a cellular setting. Overall, these deuterated probes will be powerful tools to help improve our understanding of the role played by PtdInsPnin physiology and disease.
Industrial preparation method of 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane
-
Paragraph 0042, (2019/06/13)
The invention discloses an industrial preparation method of 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane. The industrial preparation method of the 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane comprises the steps that (1) carboxylic acid monoglyceride is prepared by esterification reaction, specifically, glycerol and carboxylic acid are used as raw materials, and under the condition of acidic catalyst,the dehydration reaction is carried out under the condition of 90-150 DEG C for 0.5-4h to obtain the carboxylic acid monoglyceride; (2) ketal cyclization reaction is carried out, specifically, the carboxylic acid monoglyceride and acetone are controlled to perform the cyclization reaction at 20-50 DEG C for 0.5-3 h under the condition of acid catalyst reaction to obtain a cyclization intermediateproduct; and (3) hydrolysis reaction is carried out, specifically, the intermediate product obtained in the step (2) is added into an alkaline solution, the mixture reacts for 0.5-1 h at 20-50 DEG C,and the 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane is obtained. The industrial preparation method of the 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane has the characteristics of green and environment-friendly process, high selectivity of industrial reaction and high conversion rate of raw materials.
Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids
Joshi, Alaumy,Shaikh, Minhaj,Singh, Shubham,Rajendran, Abinaya,Mhetre, Amol,Kamat, Siddhesh S.
, p. 16953 - 16963 (2018/11/21)
Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare genetic human neurological disorder caused by null mutations to the Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. Although the role that ABHD12 plays in PHARC is understood, the thorough biochemical characterization of ABHD12 is lacking. Here, we report the facile synthesis of mono-1-(fatty)acyl-glycerol lipids of varying chain lengths and unsaturation and use this lipid substrate library to biochemically characterize recombinant mammalian ABHD12. The substrate profiling study for ABHD12 suggested that this enzyme requires glycosylation for optimal activity and that it has a strong preference for very-long-chain lipid substrates. We further validated this substrate profile against brain membrane lysates generated from WT and ABHD12 knockout mice. Finally, using cellular organelle fractionation and immunofluorescence assays, we show that mammalian ABHD12 is enriched on the endoplasmic reticulum membrane, where most of the very-long-chain fatty acids are biosynthesized in cells. Taken together, our findings provide a biochemical explanation for why very-long-chain lipids (such as lysophosphatidylserine lipids) accumulate in the brains of ABHD12 knockout mice, which is a murine model of PHARC.
Synthesis of the fatty esters of solketal and glycerol-formal: Biobased specialty chemicals
Perosa, Alvise,Moraschini, Andrea,Selva, Maurizio,Noè, Marco
, (2016/04/20)
The caprylic, lauric, palmitic and stearic esters of solketal and glycerol formal were synthesized with high selectivity and in good yields by a solvent-free acid catalyzed procedure. No acetal hydrolysis was observed, notwithstanding the acidic reaction conditions.
Microemulsion-based organogels as an efficient support for lipase-catalyzed reactions under continuous-flow conditions
Itabaiana, Ivaldo,Gonalves, Karen M.,Zoumpanioti, Maria,Leal, Ivana C. R.,Miranda, Leandro S. M. E,Xenakis, Aristotelis,De Souza, Rodrigo O. M. A.
, p. 1372 - 1376 (2015/02/19)
In this work, microemulsion-based organogels (MBGs) containing lipase are reported as an efficient catalytic system for monoacylglyceride (MAG) synthesis. More specifically, Candida antarctica lipase B (CaLB) was immobilized on an MBG matrix (MBGCaLB) formed with (hydroxypropyl)methyl cellulose as a gelling agent, and this catalyst revealed high conversion yields (expressed in grams of ester per hour per gram of enzyme) under both batch and continuous-flow conditions. Under flow conditions, 1:1 stearic acid/solketal (100 mM in n-heptane) could be converted to protected MAG (>99%) in a residence time of 11 min at 45 °C. A recycle study showed that the MBGCaLB system can be recycled 15 times without activity loss, a number 2 times higher than under batch conditions catalyzed by immobilized lipase, in agreement with green chemistry protocols.
Kinetics and mechanism of lipase catalyzed monoacylglycerols synthesis
Itabaiana Jr.,Goncalves,Cordeiro,Zoumpanioti,Leal,Miranda,De Souza,Xenakis
, p. 34 - 39 (2013/10/22)
Monoacylglycerols are increasingly used in several industrial applications as effective and cheap emulsifiers. In the present work monostearin synthesis has been studied, using lipase as a biocatalyst of the esterification reaction of stearic acid with (R,S)-1,2-O-iso-propylidene glycerol (solketal). The lipase from Candida antarctica (CaL B) was immobilized in AOT/isooctane water in oil microemulsions. Optimization of the reaction conditions have shown that the highest production (80% in 30 min) could be achieved at 40 °C, in microemulsions with relatively low water content (wo = 8). Kinetic studies have shown that the esterification reaction of stearic acid with solketal catalyzed by CaL B occurs via the ordered bi-bi mechanism, in which inhibition by the acid was identified. Moreover, at high fixed solketal concentrations a negative cooperativity is pronounced, which means that binding of the alcohol lowers the affinity of the enzyme for binding of the acid. Values of all kinetic parameters have been determined.
Optically active monoacylglycerols: Synthesis and assessment of purity
Chen, Chao-Yuan,Han, Wei-Bo,Chen, Hui-Jun,Wu, Yikang,Gao, Po
, p. 4311 - 4318 (2013/07/26)
Despite their simple structures, synthesis of 1(or 3)-acyl-sn-glycerols remains a challenge that cannot be ignored because of facile acyl migrations, which not only complicate the synthesis but also make direct GC or HPLC analysis unfeasible. Assessment of the optical purity of monoacylglycerols has, to date, relied almost exclusively on specific rotation data, which are small in value and thus insensitive to impurities. Now, a simple means to "magnify" the small specific rotations has been found, along with practical methods for the measurement of both 1,2-and 1,3-acyl migrations, which offer a convenient and straightforward alternative to Mori's NMR analysis of Mosher esters. With the aid of these methods, a range of conditions for deacetonide removal were examined en route to the synthesis of two natural monoacylglycerols. Refined hydrolysis conditions, along with useful knowledge about the solubility and reactivity of substrates with an ultra long alkyl chain are also presented. Copyright
Design and synthesis of fluorescence-labeled closo-dodecaborate lipid: Its liposome formation and in vivo imaging targeting of tumors for boron neutron capture therapy
Nakamura, Hiroyuki,Ueda, Noriko,Ban, Hyun Seung,Ueno, Manabu,Tachikawa, Shoji
experimental part, p. 1374 - 1380 (2012/04/10)
The fluorescence-labeled closo-dodecaborane lipid (FL-SBL) was synthesized from (S)-(+)-1,2-isopropylideneglycerol as a chiral starting material. FL-SBL was readily accumulated into the PEGylated DSPC liposomes prepared from DSPC, CH, and DSPE-PEG-OMe by the post insertion protocol. The boron concentrations and the fluorescent intensities of the FL-SBL-labeled DSPC liposomes increased with the increase of the additive FL-SBL, and the maximum emission wavelength of the liposomes appeared at 531 nm. A preliminary in vivo imaging study of tumor-bearing mice revealed that the FL-SBL-labeled DSPC liposomes were delivered to the tumor tissue but not distributed to hypoxic regions.
Total synthesis of a glycosylphosphatidylinositol anchor of the human lymphocyte CD52 antigen
Burgula, Srinivas,Swarts, Benjamin M.,Guo, Zhongwu
scheme or table, p. 1194 - 1201 (2012/03/26)
The first total synthesis of a glycosylphosphatidylinositol (GPI) anchor bearing a polyunsaturated arachidonoyl fatty acid is reported. This lipid is found in mammalian GPIs that do not undergo lipid remodeling, a process that has important implications in the localization and function of GPI-anchored proteins. Incorporation of the oxidation- and reduction-sensitive arachidonoyl lipid in the target GPI was accomplished by using the para-methoxybenzyl (PMB) group for permanent hydroxyl group protection, which featured a selective, rapid, and efficient global deprotection protocol. The flexibility of this synthetic strategy was further highlighted by the inclusion of two additional GPI core structural modifications present in the GPI anchor of the human lymphocyte CD52 antigen. Lipid diversity in GPI synthesis: The convergent synthesis of an arachidonoyl-containing glycosylphosphatidylinositol (GPI) anchor of the human lymphocyte CD52 antigen is reported. Incorporation of the oxidation- and reduction-sensitive polyunsaturated arachidonoyl lipid, as well as two additional GPI core modifications (see structure), was enabled by using a para-methoxybenzyl (PMB)-based global protection strategy. Copyright
