Brown's P2-Ni does the job: An efficient synthesis of tetradeuterated neuroprostane (see structure) has been accomplished by using an ene–diyne stereoselective deuteration strategy. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
A series of new model of lipophilized phenolic compound derived from the rosmarinic acid was synthesized: 1,2‐diacylglycerol rosmarinate (RDAG) with different alkyl chain lengths from five to eighteen carbons. These RDAG were obtained through a chemo‐enzymatic synthesis: A chemical esterification based on the Mitsunobu reaction, followed by a lipase‐catalyzed transesterification to link the different lipophilic moieties. The antioxidant abilities of these molecules were assessed on reactive oxygen species (ROS) overexpressing fibroblasts. The RDAG 12 displayed the best antioxidant activity of the series. Lengthening of the lipid chain beyond twelve carbon atoms leads to a decrease in the antioxidant activity, thus confirming the occurrence of a cut‐off effect. Antioxidant RDAG 12 activity was then compared with that of vitamins C and E, rosmarinic acid and decyl rosmarinate (R 10 ). The order of activity was R 10 > RDAG 12 > RDAG 5 > rosmarinic acid ∼ vitamin C ∼ vitamin E. At 5 μM, R 10 exhibited an even better antioxidant activity than the combination of vitamins C and E at 5 μM each. These results confirm, firstly, that catechol structure is very effective in terms of antioxidant activity and secondly, that linking an appropriate hydrophobic domain is a powerful strategy to synthesize effective antioxidants. Practical applications: Phenolic compounds (especially phenolic acids and flavonoids) are potent antioxidants that may play an important role as well in biological system (to prevent some risk factors associated with cancers, cardiovascular, and neurodegenerative diseases) as in formulated‐lipid dispersions. However, their activity is often limited by low solubility and stability in such systems. Lipophilization of phenolic compounds may increase their solubility in lipophilic matrices, conferring better antioxidant protection for food or non‐food application. In biological system, lipophilization may contribute to easier penetration of antioxidants through lipid bilayer of cell membranes, which can significantly increase their bioavailability. Thus, lipophilic phenolic derivatives provide a perspective of substances with maintained or improved biological properties for food, cosmetic, and pharmaceutical applications, playing an important role in the development of new drugs or food additives. A series of new model of lipophilized phenolic compound (1,2‐diacylglycerol rosmarinate, RDAG) were synthesized through a chemo‐enzymatic synthesis. In terms of antioxidant activity assessed in fibroblasts, all synthesized RDAG exhibited higher ROS inhibition level than free rosmarinic acid. RDAG with two lauryl chains (RDAG 12 ) displayed the best antioxidant ability of the series, with higher activity than vitamins E and C. These results confirm that linking an appropriate hydrophobic domain is a powerful strategy to synthesize effective antioxidants.
An efficient regiospecific total synthesis of several branched fatty acyl hydroxyl-fatty acids (FAHFA) has been achieved from available terminal alkenes and alkynes. The key steps feature a boron trifluoride mediated epoxide ring opening with acetylide carbanions, followed by hydrogenation of the alkyne function. The carboxylic acid of the hydroxylated chains is introduced at the last step of the synthesis to allow the esterification of the branched hydroxyl group by fatty acids beforehand. The chemical syntheses of a "linear" FAHFA and a branched FAHFA analog containing a Z-olefin in the hydroxyl-fatty acid chain are also reported. A LC-MS/MS method has been developed. Several reversed phase columns were compared. Regioisomers were separated.
Octadecanoids are broadly defined as oxylipins (i.e., lipid mediators) derived from 18-carbon fatty acids. In contrast to the well-studied eicosanoids, there is a lack of analytical methods for octadecanoids, hampering further investigations in the field. We developed an integrated workflow combining chiral separation by supercritical fluid chromatography (SFC) and reversed-phase liquid chromatography (LC) coupled to tandem mass spectrometry detection for quantification of a broad panel of octadecanoids. The platform includes 70 custom-synthesized analytical and internal standards to extend the coverage of the octadecanoid synthetic pathways. A total of 103 octadecanoids could be separated by chiral SFC and complex enantioseparations could be performed in <13 min, while the achiral LC method separated 67 octadecanoids in 13.5 min. The LC method provided a robust complementary approach with greater sensitivity relative to the SFC method. Both methods were validated in solvent and surrogate matrix in terms of linearity, lower limits of quantification (LLOQ), recovery, accuracy, precision, and matrix effects. Instrumental linearity was good for both methods (R2 > 0.995) and LLOQ ranged from 0.03 to 6.00 ng/mL for SFC and 0.01 to 1.25 ng/mL for LC. The average accuracy in the solvent and surrogate matrix ranged from 89 to 109% in SFC and from 106 to 220% in LC, whereas coefficients of variation (CV) were <14% (at medium and high concentrations) and 26% (at low concentrations). Validation in the surrogate matrix showed negligible matrix effects (<16% for all analytes), and average recoveries ranged from 71 to 83%. The combined methods provide a platform to investigate the biological activity of octadecanoids and expand our understanding of these little-studied compounds.
Research Articles| July 23 2009 Evaluation of Metopiron and ACTH Tests in Prolonged Corticosteroid Treatment of Chronic Asthma Subject Area: Immunology and Allergy N. Lass; N. Lass Municipal Hospital 'Hadassa', Tel-Aviv Search for other works by this author on: This Site PubMed Google Scholar L. Laurian; L. Laurian Municipal Hospital 'Hadassa', Tel-Aviv Search for other works by this author on: This Site PubMed Google Scholar L. Balas L. Balas Municipal Hospital 'Hadassa', Tel-Aviv Search for other works by this author on: This Site PubMed Google Scholar International Archives of Allergy and Applied Immunology (1969) 36 (1-2): 180–185. https://doi.org/10.1159/000230739 Article history Published Online: July 23 2009 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation N. Lass, L. Laurian, L. Balas; Evaluation of Metopiron and ACTH Tests in Prolonged Corticosteroid Treatment of Chronic Asthma. International Archives of Allergy and Applied Immunology 31 December 1969; 36 (1-2): 180–185. https://doi.org/10.1159/000230739 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsInternational Archives of Allergy and Applied Immunology Search Advanced Search Article PDF first page preview Close Modal 1969Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.
Differential mobility spectrometry (DMS) is capable of separating stereoisomeric molecular ions based on their mobility in an oscillating electrical field with an asymmetric waveform. Thus, it is an "orthogonal" technique to chromatography and (tandem) mass spectrometry. Bioactive lipids, particularly of the eicosanoid and docosanoid class feature numerous stereoisomers, which exhibit a highly specific structure-activity relationship. Moreover, the geometry of these compounds also reflects their biochemical origin. Therefore, the unambiguous characterization of related isomers of the eicosanoid and docosanoid classes is of fundamental importance to the understanding of their origin and function in many biological processes. Here we show, that SelexION DMS technology coupled to μLC-MS/MS is capable of differentiating at least five closely related leukotrienes partially coeluting and (almost) unresolvable using LC-MS/MS only. We applied the developed method to the separation of LTB4 and its coeluting isomer 5S,12S-diHETE in murine peritoneal exudate cells, showing that LTB4 is present only after zymosan A injection while its isomer 5S,12S-diHETE is produced after saline (PBS) administration. Additionally, we show that the SelexION technology can also be applied to the separation of PD1 and PDX (10S,17S-diHDHA), two isomeric protectins.
