3317-99-5Relevant academic research and scientific papers
Synthesis of ten members of the maradolipid family; Novel diacyltrehalose glycolipids from caenorhabditis elegans
P?ssler, Ulrike,Gruner, Margit,Penkov, Sider,Kurzchalia, Teymuras V.,Kn?lker, Hans-Joachim
, p. 2482 - 2486 (2011)
The synthesis of ten members of the maradolipid family is described using a direct route starting from trehalose. Georg Thieme Verlag Stuttgart · New York.
Direct synthesis of maradolipids and other trehalose 6-monoesters and 6,6′-diesters
Paul, Nawal K.,Twibanire, Jean-D'Amour K.,Grindley, T. Bruce
, p. 363 - 369 (2013)
It was shown that reaction of trehalose with 1 equiv of a fatty acid in pyridine promoted by 1 equiv of the uronium-based coupling agent 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) at room temperature gives a good yield of the primary ester accompanied by small amounts of the diprimary ester using hexanoic, palmitic, and oleic acids as examples. Reactions using 2 equiv of the fatty acids gave the symmetrical diesters. The monoesters were reacted with different fatty acids to give nonsymmetric 6,6′-diesters in very good yields. Compounds synthesized include the most abundant component of the very complex maradolipid mixture, 6-O-(13-methyltetradecanoyl)-6′-O-oleoyltrehalose, and a component potentially present in this mixture, 6-O-(12-methyltetradecanoyl)-6′-O- oleoyltrehalose, a derivative of an ante fatty acid. The C5-C6 rotameric populations of 6-O-monoesters, symmetrical 6,6′-diesters, and 2,6,6′-triesters of fatty acids were calculated from the values of the H5-H6R and H5-H6S coupling constants and found to be similar to those found for glucose. The rotameric populations of the monosubstituted glucose residues in the 2,6,6′-triesters was altered considerably to favor the gt rotamer, presumably because of attraction between the 2- and 6′-fatty acid chains.
Improved Synthesis of 'Cord Factor' Analogues
Bottle, Steven,Jenkins, Ian D.
, p. 385 (1984)
Treatment of trehalose or sucrose with triphenylphosphine, di-isopropyl azodicarboxylate, and palmitic acid results in the formation of the corresponding 6,6'-dipalmitates-analogues of 'cord factor' - in good yield under exceptionally mild conditions.
A Virulence-Associated Glycolipid with Distinct Conformational Attributes: Impact on Lateral Organization of Host Plasma Membrane, Autophagy, and Signaling
Dadhich, Ruchika,Mishra, Manjari,Ning, Shangbo,Jana, Santanu,Sarpe, Vikram A.,Mahato, Jaladhar,Duan, Mojie,Kulkarni, Suvarn S.,Kapoor, Shobhna
, p. 740 - 750 (2020)
Mycobacterium tuberculosis (Mtb) serves as the epitome of how lipids-next to proteins- A re utilized as central effectors in pathogenesis. It synthesizes an arsenal of structurally atypical lipids (C60-C90) to impact various membrane-dependent steps involved in host interactions. There is a growing precedent to support insertion of these exposed lipids into the host membrane as part of their mode of action. However, the vital role of specific virulence-associated lipids in modulating cellular functions by altering the host membrane organization and associated signaling pathways remain unanswered questions. Here, we combined chemical synthesis, biophysics, cell biology, and molecular dynamics simulations to elucidate host membrane structure modifications and modulation of membrane-associated signaling using synthetic Mycobacterium tuberculosis sulfoglycolipids (Mtb SL). We reveal that Mtb SL reorganizes the host cell plasma membrane domains while showing higher preference for fluid membrane regions. This rearrangement is governed by the distinct conformational states sampled by SL acyl chains. Physicochemical assays with SL analogues reveal insights into their structure-function relationships, highlighting specific roles of lipid acyl chains and headgroup, along with effects on autophagy and cytokine profiles. Our findings uncover a mechanism whereby Mtb uses specific chemical moieties on its lipids to fine-tune host lipid interactions and confer control of the downstream functions by modifying the cell membrane structure and function. These findings will inspire development of chemotherapeutics against Mtb by counteracting their effects on the host-cell membrane.
An improved synthesis of trehalose 6-mono- and 6,6'-di-corynomycolates and related esters
Datta, Arun K.,Takayama, Kuni,Nashed, Mina A.,Anderson, Laurens
, p. 95 - 109 (2007/10/02)
A simplified synthesis of 6-mono- and 6,6'-di-corynomycolate esters of α,α-trehalose, and related compounds, was achieved by coupling the (hydroxyl-protected) acids to the partially trimethylsilylated sugar in the presence of dicyclohexylcarbodiimide and 4-dimethylaminopyridine.As acid reactants, (2-RS,3-RS)-3-hydroxy-2-tetradecyloctadecanoic acid (DL-corynomycolic acid) and its 2RS, 3SR diastereomer were prepared from methyl palmitate by sequential Claisen condensation, reduction, chromatographic separation, and saponification.Reaction with tert-butylchlorodimethylsilane (imidazole) gave the disubstituted ether-esters, which were converted into the required 3-tert-butyldimethylsilyl ethers by partial hydrolysis. 6-Linked monocorynomycolate was obtained in excellent yield (78percent) from the reaction of the RS,SR acid with the known heptakis-O-(trimethylsilyl)trehalose, and in good yield from equimolar portions of RS,RS acid and hexakis-O-(trimethylsilyl)trehalose.An excess (2.5-molar portions) of the RS,RS acid gave the 6,6'-diester (69percent).The mono- and di-palmitate were similarly obtained from (Me3Si)6-trehalose.The mono (RS,RS)-(Me3Si)6-trehalose coupling product was partially resolved on a silica gel column into its RR and SS diastereomers, the former corresponding to the naturally occurring trehalose monocorynomycolate.All coupling products were deprotected to free trehalose esters by treatment first with K2CO3 in methanol, then tetrabutylammonium fluoride-trifluoracetic acid in oxolane.
