109786-76-7Relevant academic research and scientific papers
First synthesis of natural phosphatidyl-β-d-glucoside
Greimel, Peter,Ito, Yukishige
, p. 3562 - 3566 (2008)
Herein, we report the chemical synthesis of naturally occurring mammalian phosphatidyl-β-d-glucoside (PtdGlc), in order to confirm the proposed structure and to clarify its stereochemistry. We designed a convergent synthetic strategy, suitable to prepare
The Chiral Target of Daptomycin Is the 2R,2′S Stereoisomer of Phosphatidylglycerol
Moreira, Ryan,Taylor, Scott D.
, (2021/12/09)
Daptomycin (dap) is an important antibiotic that interacts with the bacterial membrane lipid phosphatidylglycerol (PG) in a calcium-dependent manner. The enantiomer of dap (ent-dap) was synthesized and was found to be 85-fold less active than dap against
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.
Stereospecific synthesis of phosphatidylglycerol using a cyanoethyl phosphoramidite precursor
Storch, Judith,Struzik, Zachary J.,Thompson, David H.,Weerts, Ashley N.
, (2020/07/03)
Phosphatidylglycerols (PG) are a family of naturally occurring phospholipids that are responsible for critical operations within cells. PG are characterized by an (R) configuration in the diacyl glycerol backbone and an (S) configuration in the phosphoglycerol head group. Herein, we report a synthetic route to provide control over the PG stereocenters as well as control of the acyl chain identity.
Synthesis and structure-activity relationships of varied ether linker analogues of the antitubercular drug (6 S)-2-nitro-6-{[4-(trifluoromethoxy) benzyl]oxy}-6,7-dihydro-5 H -imidazo[2,1- b ][1,3]oxazine (PA-824)
Thompson, Andrew M.,Sutherland, Hamish S.,Palmer, Brian D.,Kmentova, Iveta,Blaser, Adrian,Franzblau, Scott G.,Wan, Baojie,Wang, Yuehong,Ma, Zhenkun,Denny, William A.
scheme or table, p. 6563 - 6585 (2011/12/02)
New analogues of antitubercular drug PA-824 were synthesized, featuring alternative side chain ether linkers of varying size and flexibility, seeking drug candidates with enhanced metabolic stability and high efficacy. Both α-methyl substitution and removal of the benzylic methylene were broadly tolerated in vitro, with a biaryl example of the latter class exhibiting an 8-fold better efficacy than the parent drug in a mouse model of acute Mycobacterium tuberculosis infection and negligible fragmentation to an alcohol metabolite in liver microsomes. Extended linkers (notably propenyloxy, propynyloxy, and pentynyloxy) provided greater potencies against replicating M. tb (monoaryl analogues), with propynyl ethers being most effective under anaerobic (nonreplicating) conditions (mono/biaryl analogues). For benzyloxybenzyl and biaryl derivatives, aerobic activity was maximal with the original (OCH2) linker. One propynyloxy-linked compound displayed an 89-fold higher efficacy than the parent drug in the acute model, and it was slightly superior to antitubercular drug OPC-67683 in a chronic infection model.
New fluorescent probes reveal that flippase-mediated flip-flop of phosphatidylinositol across the endoplasmic reticulum membrane does not depend on the stereochemistry of the lipid
Vishwakarma, Ram A.,Vehring, Stefanie,Mehta, Anuradha,Sinha, Archana,Pomorski, Thomas,Hermann, Andreas,Menon, Anant K.
, p. 1275 - 1283 (2007/10/03)
Glycerophospholipid flip-flop across biogenic membranes such as the endoplasmic reticulum (ER) is a fundamental feature of membrane biogenesis. Flip-flop requires the activity of specific membrane proteins called flippases. These proteins have yet to be i
Synthetic approaches to heavily lipidated phosphoglyceroinositides
Schlueter, Urs,Lu, Jun,Fraser-Reid, Bert
, p. 255 - 257 (2007/10/03)
(Matrix presented) Naturally occurring phosphoinositide glycoconjugates are equipped with varied acyl residues that are important for their biological activity and biosynthesis. This paper reports that acylation at O2 of the myo-inositol moiety can be ach
Convergent synthesis of antiparallel cyclobolaphiles having two diacetylenes: Mimetics of membrane components that are found in archaea
Miyawaki, Kazuhiro,Goto, Rie,Takagi, Toshiyuki,Shibakami, Motonari
, p. 1467 - 1470 (2007/10/03)
Chiral 48-membered antiparallel cyclobolaphiles and their diastereomer having two diacetylenes were convergently synthesized utilizing both cross-coupling method (Cul, pyrrolidine) and Glaser intramolecular cyclization, starting from commercially available D- and L-1, 2-O-isopropylidene-sn-glycerol as chiral sources.
Efficient synthesis of parallel cyclobolaphiles having two diacetylenes: Mimetics of archaeal membrane lipids
Miyawaki, Kazuhiro,Takagi, Toshiyuki,Shibakami, Motonari
, p. 1326 - 1328 (2007/10/03)
Chiral 48-membered parallel cyclobolaphiles and their diastereomer having two diacetylenes were efficiently synthesized by utilizing both the selective deprotection and the cross-coupling method of two distinct acetylenic compounds.
