Phosphonolipids. XXVI. Mixed-Acid Phosphonocephalins: Synthesis of α′-Stearoyl- β-oleoyl-L-α-glyceryl-(2-aminoethyl)phosphonate

1974 ◽  
Vol 52 (7) ◽  
pp. 570-574 ◽  
Author(s):  
Erich Baer
Keyword(s):  
Fatty Acid ◽  
Phosphonic Acid ◽  
Glycerol Moiety ◽  
Mixed Acid ◽  
New Class ◽  
Naturally Occurring ◽  
Acid Analogue

The synthesis of α′-stearoyl-β-oleoyl-L-α-glyceryl-(2-aminoethyl)phosphonate is reported. It is a member of a new class of phosphonolipids containing two dissimilar fatty acid substituents, one of which is unsaturated and occupies the 2 or β position of the glycerol moiety. The mixed-acid phosphonolipid, a phosphonic acid analogue of naturally occurring L-(α-stearoyl-β-oleoyl)cephalin, was obtained by phosphonylating D-α-stearoyl-β-oleoylglycerol with (2-phthalimidoethyl) phosphonic acid monochloride and triethylamine, and freeing the resulting α-stearoyl-β-oleoyl-L-α-glyceryl-(2-phthalirnidoethyl)phosphonate of its protective phthaloyl group by hydrazinolysis.

Phosphonolipids. XV. Synthesis of a dihydroceramide aminoethylphosphonate

1968 ◽  
Vol 46 (3) ◽  
pp. 525-532 ◽  
Author(s):  
Erich Baer ◽  
Bimal C. Pal
Keyword(s):  
Chemical Synthesis ◽  
Acid Chloride ◽  
Phosphonic Acid ◽  
Steam Distillation ◽  
Free Acid ◽  
Reaction Products ◽  
New Class ◽  
Naturally Occurring ◽  
Benzoyl Group ◽  
Complex Lipids

The first chemical synthesis of a dihydroceramide aminoethylphosphonate is described. It is a saturated representative of a new class of recently discovered, naturally occurring complex lipids derived from phosphonic acid. The compound, viz. erythro-N-palmitoyl-DL-dihydrosphingosyl-1-(2-aminoethyl)-phosphonate, was obtained by two procedures: phosphonylation of erythro-N-palmitoyl-3-O-benzoyl-DL-dihydrosphingosine with (2-N,N-dibenzylammoethyl)phosphonic acid chloride (hydrochloride) and triethylamine, or with (2-phthalimidoethyl)phosphonic acid monochloride and triethylamine, and freeing the reaction products of both procedures, viz. erythro-N-palmitoyl-3-O-benzoyl-DL-dihydrosphingosyl-1-(2-N,N-dibenzylaminoethyl)phosphonate and erythro-N-palmitoyl-3-O-benzoyl-DL-dihydrosphingosyl-1-(2-phthalimidoethyl)phosphonate, from their protective benzyl or phthaloyl group by hydrogenolysis or hydrazinolysis, respectively, followed in both cases by removal of the benzoyl group by saponification.The (2-N,N-dibenzylaminoethyl)phosphonic acid was obtained by treating (2-bromoethyl)phosphonic acid with N,N-dibenzylamine and converting the reaction product, viz. the dibenzylammonium salt of (2-N,N-dibenzylaminoethyl)phosphonic acid, into the free acid by steam distillation.

Synthesis of Glycerol-1,3-diphosphonic Acid

1973 ◽  
Vol 51 (8) ◽  
pp. 1203-1205 ◽  
Author(s):  
Ranga Robinson ◽  
Erich Baer
Keyword(s):  
Acid Hydrolysis ◽  
Phosphonic Acid ◽  
Hydrobromic Acid ◽  
Condensation Product ◽  
Triethyl Phosphite ◽  
Phosphate Esters ◽  
Glyceric Acid ◽  
Diphosphonic Acid ◽  
Naturally Occurring ◽  
Acid Analogue

The synthesis of glycerol-1,3-diphosphonic acid, the phosphonic acid analogue of the naturally occurring glycerol-1,3-diphosphoric acid, is described. The phosphonic acid analogue was obtained in an overall yield of 29.7%, by heating a mixture of 1,3-dibromo-2-hexadecanoyloxypropane and triethyl phosphite to 140° for 48 h, distilling off in vacuo the excess of triethyl phosphite, hydrolyzing the condensation product, 1,3-bis(diethylphosphono)-2-hexadecanoyloxypropane, with 2 N hydrobromic acid at 100° for 5 h, and isolating the glycerol-1,3-diphosphonic acid in form of the dibarium salt. The glycerol-1,3-diphosphonate differs from glycerol-1,3-diphosphate and other phosphate esters of glycerol and glyceric acid by its greater stability towards acid hydrolysis. The glycerol-1,3-diphosphonic acid is readily distinguished from glycerol-1,3-diphosphoric acid and glycerol-1,2-diphosphoric acid by paper chromatography.

scholarly journals Lipid disequilibrium disrupts ER proteostasis by impairing ERAD substrate glycan trimming and dislocation

2017 ◽  
Vol 28 (2) ◽  
pp. 270-284 ◽  
Author(s):  
Milton To ◽  
Clark W. H. Peterson ◽  
Melissa A. Roberts ◽  
Jessica L. Counihan ◽  
Tiffany T. Wu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Mammalian Cells ◽  
26S Proteasome ◽  
Unfolded Protein ◽  
Acid Analogue ◽  
Triacsin C ◽  
Chain Acyl ◽  
Dependent Cell ◽  
Outstanding Question ◽  
The Unfolded Protein Response

The endoplasmic reticulum (ER) mediates the folding, maturation, and deployment of the secretory proteome. Proteins that fail to achieve their native conformation are retained in the ER and targeted for clearance by ER-associated degradation (ERAD), a sophisticated process that mediates the ubiquitin-dependent delivery of substrates to the 26S proteasome for proteolysis. Recent findings indicate that inhibition of long-chain acyl-CoA synthetases with triacsin C, a fatty acid analogue, impairs lipid droplet (LD) biogenesis and ERAD, suggesting a role for LDs in ERAD. However, whether LDs are involved in the ERAD process remains an outstanding question. Using chemical and genetic approaches to disrupt diacylglycerol acyltransferase (DGAT)–dependent LD biogenesis, we provide evidence that LDs are dispensable for ERAD in mammalian cells. Instead, our results suggest that triacsin C causes global alterations in the cellular lipid landscape that disrupt ER proteostasis by interfering with the glycan trimming and dislocation steps of ERAD. Prolonged triacsin C treatment activates both the IRE1 and PERK branches of the unfolded protein response and ultimately leads to IRE1-dependent cell death. These findings identify an intimate relationship between fatty acid metabolism and ER proteostasis that influences cell viability.

2,2-Dialkylacetic Acids -A New Class of Naturally Occurring Lipid Constituents

1995 ◽  
Vol 50 (1-2) ◽  
pp. 123-126 ◽  
Author(s):  
Gottfried Raab ◽  
Jürgen Jacob
Keyword(s):  
Retention Time ◽  
Relative Retention Time ◽  
Methyl Esters ◽  
South American ◽  
Time Data ◽  
New Class ◽  
The Past ◽  
Relative Retention ◽  
Naturally Occurring ◽  
Acetic Acids

Abstract The uropygial gland waxes of the South American red-legged Seriema (Cariama cristata (L., 1766)) were found to be composed of unbranched alcohols and 2,2′-dialkyl-substituted acetic acids which so far have not been found in skin lipids. When used as a chemosystematic character, the occurrence of this lipid class separates the order Cariamiformes (Seriemas) from all other avian orders hitherto investigated, especially from the Gruiformes (cranes and rails) to which they have been tentatively attributed in the past. From the GC retention time data now available for a series of 2-alkyl-substituted fatty acid methyl esters relative retention time indices for other compounds may be predicted.

scholarly journals Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Sara I Liin ◽  
Johan E Larsson ◽  
Rene Barro-Soria ◽  
Bo Hjorth Bentzen ◽  
H Peter Larsson
Keyword(s):  
Fatty Acid ◽  
Long Qt Syndrome ◽  
Molecular Mechanisms ◽  
Loss Of Function ◽  
Long Qt ◽  
Acid Analogue ◽  
Fatty Acid Analogue ◽  
Qt Syndrome ◽  
Channel Currents ◽  
Iks Channel

About 300 loss-of-function mutations in the IKs channel have been identified in patients with Long QT syndrome and cardiac arrhythmia. How specific mutations cause arrhythmia is largely unknown and there are no approved IKs channel activators for treatment of these arrhythmias. We find that several Long QT syndrome-associated IKs channel mutations shift channel voltage dependence and accelerate channel closing. Voltage-clamp fluorometry experiments and kinetic modeling suggest that similar mutation-induced alterations in IKs channel currents may be caused by different molecular mechanisms. Finally, we find that the fatty acid analogue N-arachidonoyl taurine restores channel gating of many different mutant channels, even though the mutations are in different domains of the IKs channel and affect the channel by different molecular mechanisms. N-arachidonoyl taurine is therefore an interesting prototype compound that may inspire development of future IKs channel activators to treat Long QT syndrome caused by diverse IKs channel mutations.

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