Synthesis of ether glyceroglycolipids

The reaction of 1-O-aklyl-2-O-methylglycerols with acetobromosugars in the presence of mercury(II)cyanide leads to stereochemically uniform peracetylated 1-O-aklyl-2-O-methyl-3-O-β-D-glycosylglycerols after column chromatography. Alkaline hydrolysis of the latter compounds affords 1-O-alkyl-2-O-methyl-3-O-β-D-glycosylglycerols, i.e. ether glyceroglycolipids with potential antineoplastic activity. The sequence of reactions described is also applicable to the preparation of radioactively labeled ether glyceroglycolipids in high yields     

Biodegradation of the gasoline oxygenates methyl tert-butyl ether, ethyl tert-butyl ether, and tert-amyl methyl ether by propane-oxidizing bacteria.

Several propane-oxidizing bacteria were tested for their ability to degrade gasoline oxygenates, including methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME). Both a laboratory strain and natural isolates were able to degrade each compound after growth on propane. When propane-grown strain ENV425 was incubated with 20 mg of uniformly labeled [14C]MTBE per liter, the strain converted > 60% of the added MTBE to 14CO2 in < 30 h. The initial oxidation of MTBE and ETBE resulted in the production of nearly stoichiometric amounts of tert-butyl alcohol (TBA), while the initial oxidation of TAME resulted in the production of tert-amyl alcohol. The methoxy methyl group of MTBE was oxidized to formaldehyde and ultimately to CO2. TBA was further oxidized to 2-methyl-2-hydroxy-1-propanol and then 2-hydroxy isobutyric acid; however, neither of these degradation products was an effective growth substrate for the propane oxidizers. Analysis of cell extracts of ENV425 and experiments with enzyme inhibitors implicated a soluble P-450 enzyme in the oxidation of both MTBE and TBA. MTBE was oxidized to TBA by camphor-grown Pseudomonas putida CAM, which produces the well-characterized P-450cam, but not by Rhodococcus rhodochrous 116, which produces two P-450 enzymes. Rates of MTBE degradation by propane-oxidizing strains ranged from 3.9 to 9.2 nmol/min/mg of cell protein at 28 degrees C, whereas TBA was oxidized at a rate of only 1.8 to 2.4 nmol/min/mg of cell protein at the same temperature.     

Variability of crown ether toxicity

Crown ethers are toxic to Escherichia coli. At a sublethal dosage, the crown ether affects the three phases in the bacterial growth curve as evidenced by an appearance of a lag period, an occasional decrease in the stationary phase at a lower microbial population. Potassium ion but not sodium ion can reduce the lag induced by the presence of 18-crown-6. On the contrary, the presence of either potassium ion or sodium ion lengthens the lag due to substituted 18-crown-6 ethers. Explanations to this variable toxicity are proposed.     

Chain substituted polymerizable ether lipids: synthesis of sorbyl and diacetylenic ether glycerophosphocholine.

Three novel polymerizable ether lipids, 1,2-O-bis[10(2',4'-hexadienoyloxy)decyl]-rac, 1,2-O-bis(10,12-tricosadiynyl)-rac, and (-)-2,3-O-bis(10,12-tricosadiynyl)-sn-glycero-1-phosphocholine, were synthesized from 3-O-benzyl-rac, 3-O-trityl-rac and (-)-1-O-trityl-sn-glycerol as starting materials, respectively. All the reactions employed in these multi-step syntheses are straightforward giving an overall yield of 21% for the sorbyl, 42% for the racemic diacetylenic and 44% for the chiral diacetylenic lipid. All the lipids form bilayer assemblies on hydration and show transitions from gel to liquid-crystalline phases at 11.4 degrees, 27.6 degrees and 30.0 degrees C, respectively. Bilayer assemblies of each are photoreactive and are readily polymerized by irradiation with 254 nm light. Tubules of the chiral diacetylenic ether lipid were observed.     

Inhibitors of ether lipid biosynthesis

During biosynthesis of ether lipids, fatty alcohols may add covalently to ene-diol esters that would result from isomerization of acyl-dihydroxyacetone phosphate. Palmitoylation of 1,2,3-trihydroxyeicosane 1-phosphate, obtained by epoxidation of the product obtained by vinyllithiation of octadecanal, yields stable analogs of the high-energy intermediates that would be expected to result from alcohol addition. These analogs, in which an alkyl group replaces the ether alkoxyl group of the intermediates, inhibit formation of hexadecyl-dihydroxyacetone phosphate in a microsomal system from Ehrlich ascites cells. The parent compound is without effect.     

Biodegradation of gasoline ether oxygenates

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Highlights► The different types of MTBE and TBA-degrading microorganisms are summarized. ► The pathways involved in aerobic and anaerobic MTBE biodegradation are described. ► The roles of key and novel enzymes in these processes are highlighted. ► The impacts of biochemical studies on stable isotope-based analyses are discussed.     

Biodegradation of ethyl t-butyl ether (ETBE), methyl t-butyl ether (MTBE) and t-amyl methyl ether (TAME) by Gordonia terrae

Gordonia terrae strain IFP 2001 was selected from activated sludge for its capacity to grow on ethyl t-butyl ether (ETBE) as sole carbon and energy source. ETBE was stoichiometrically degraded to t-butyl alcohol (TBA) and the activity was inducible. A constitutive strain, G. terrae IFP 2007, derived from strain IFP 2001, was also selected. Methyl t-butyl ether (MTBE) and t-amyl methyl ether (TAME) were not used as carbon and energy sources by the two strains, but cometabolic degradation of MTBE and TAME was demonstrated, to TBA and t-amyl alcohol (TAA) respectively, in the presence of a carbon source such as ethanol. No two-carbon compound was detected during growth on ETBE, but formate was produced during cometabolic degradation of MTBE or TAME. A monooxygenase was involved in the degradation of ethers, because no degradation of ETBE was observed under anaerobic conditions and the presence of a cytochrome P-450 was demonstrated in G. terrae IFP 2001 after induction by cultivation on ETBE.     

Stereochemical specificity of the biosynthesis of the alkyl ether bond in alkyl ether lipids.

The stereochemical course of the formation of the alkyl ether bond in alkyl ether lipids was investigated through the synthesis of stereospecifically labeled acyl R- or S-[1-3H]dihydroxyacetone 3-phosphate (DHAP) starting from L-glyceraldehyde. It was demonstrated directly that the formation of the alkyl ether bond results in the stereospecific exchange of the pro-R C-1 hydrogen of DHAP with a proton of water. The configuration of the hydrogen that is retained on C-1 after formation of the alkyl ether bond was also investigated. The alkyl ether lipid was degraded, and the DHAP backbone isolated as glycerol, converted to DHAP via glycerol 3-phosphate and treated with either aldolase or triose phosphate isomerase. The results demonstrated that the retained hydrogen on C-1, which was pro-S in the starting substrate, was pro-S in the product alkyl ether.     

Diaryl ether inhibitors of farnesyl-protein transferase

Imidazolemethyl diaryl ethers are potent inhibitors of farnesyl-protein transferase. The SNAr displacement reaction used to prepare these diaryl ethers was amenable to rapid parallel synthesis of FPTase inhibitors. The use of a broad range of commercially available phenols quickly identified compounds which proved active in cells.     

Exogenous ether lipids predominantly target mitochondria

Ether lipids are ubiquitous constituents of cellular membranes with no discrete cell biological function assigned yet. Using fluorescent polyene-ether lipids we analyzed their intracellular distribution in living cells by microscopy. Mitochondria and the endoplasmic reticulum accumulated high amounts of ether-phosphatidylcholine and ether-phosphatidylethanolamine. Both lipids were specifically labeled using the corresponding lyso-ether lipids, which we established as supreme precursors for lipid tagging. Polyfosine, a fluorescent analogue of the anti-neoplastic ether lipid edelfosine, accumulated to mitochondria and induced morphological changes and cellular apoptosis. These data indicate that edelfosine could exert its pro-apoptotic power by targeting and damaging mitochondria and thereby inducing cellular apoptosis. In general, this study implies an important role of mitochondria in ether lipid metabolism and intracellular ether lipid trafficking.     

Monolayers of ether lipids from archaebacteria

The surface behavior of six different ether lipids from archaebacteria, based on condensation of glycerol or more complex polyols with two isoprenoid alcohols at 20 or 40 carbon atoms, was investigated in monolayers at the air-water interface.The compounds with no complex polar group (GD, GDGT, GDNT) form monolayers showing a reversible collapse at surface pressure as low as 22 dynes/cm. This collapse pressure decrease with temperature in such a way that the film tension remains constant. In condensed films, these molecules do not assume a completely upright position.Lipids with complex polar ends (HL, GLB, PLII) form films more stable to compression. Forcearea characteristics and surface moment values of HL monolayers are similar to those of analogous ester lipids with fatty acid chains. Monolayers of the two bipolar lipids, GLB and PLII, at room temperature present a more condensed state, probably due to the lateral cohesion between long alkyl chains, but a lower collapse pressure.For all bipolar lipids, the area expansion induced by temperature increase is larger than that of monopolar ones.Abbreviations GD Glycerol diether (2,3-di-O-phytanyl-sn-glycerol - GDGT Glycerol-dialkyl-glycerol tetraether - GDNT Glycerol-dialkyl-nonitol tetraether - GLB Glycolipid B - PLII Phospholipid II - HL Total lipid extract from Halobacterium halobium     

Synthesis of glycerol 1,3-dihexadecyl ether

The synthesis of 1,3-dihexadecyloxy-2-propanol (glycerol 1,3-dihexadecyl ether) is reported. The method is applicable to the preparation of other 1,3-disubstituted glycerols where the substituents are not affected by acid or by catalytic hydrogenolysis conditions.     

Structural studies on santalin permethyl ether

The chloroform extract of the heartwood of Pterocarpus santalinus yielded a mixture of red pigments which could be separated by polyamide column chromatography into two major compounds, santalin-A and santalin-B. Both gave the same permethyl ether, C₃₈H₃₆O₁₀ which had 8 methoxyls and formed a number of derivatives typical of anhydrobenzopyranols. IR and UV spectra confirmed the same. NMR and MS suggested the presence of homoveratrayl group supported by the formation of veratraldehyde in alkali degradation. Permanganate oxidation gave 2,4-dimethoxy benzoic acid, veratric acid and 3,4,6-trimethoxy phthalic acid. On a basic fluorone skeleton, the substituents in the A ring are indicated by 2,4-dihydroxy-5-methoxy benzaldehyde, an alkali fission product and, further, 2,4-dimethoxy phenyl and homoveratryl units are located in ring C based on NMR, MS and biogenetic considerations. The residues constitute another benzene ring fused to ring C leading to the complete structures of the permethyl ether as (VII) which explains all its degradations and which constitutes a highly condensed biflavonoid of a new type.