Ether lipids based on the glyceryl ether skeleton: Present state,future potential

Lipids from natural sources consist mainly of saponifiable substances, such as glycerides, along with some unsaponifiable lipids, some of which are ether lipids. Typical ether lipids are monoalkyl ethers of glycerin, also called alkyl/alkenyl glyceryl ethers. Alkyl/alkenyl glyceryl ethers have also been reported in marine organisms and in human feces. Several chemical syntheses of such ether lipids have been reported. Typical examples are alkyl glyceryl ether formation by the addition reaction of alkyl glycidyl ether and the telomerization reaction of butadiene with glycerin and a transition metal catalyst. Characteristic chemical structures, such as terpene alkyl glyceryl ethers, archaebacterial macrocyclic ether lipids, and glyceryl ethers of condensed cyclic planar molecules, have been obtained as well. Over the past few decades, industry has shown much interest in the chemistry and application of highly branched fatty acids. For example, isostearyl glyceryl ether (GE-IS) with methyl branching in the middle chain was already known, but it is now prepared at an industrial scale by proprietary alkyl glycidyl ether methods. The characteristic behavior of GE-IS toward water, such as formation of water-in-oil emulsions containing large amounts of water and of liquid crystals, has made it applicable for use in hair and skin-care cosmetics. Based on these studies and considerations, glyceryl ether lipids, which are rarely investigated, may become one of the most important and useful lipids in the industry.     

Applications of protecting groups in the synthesis of surfactants, lipids, and related compounds

Several types of alkyl ether lipids were prepared in high yield and high purity using protecting groups such as 1,3-dioxolane compounds or allyl ethers. We also succeeded in the industrial production of alkyl glyceryl ethers using the reaction of alkyl glycidyl ethers with acetone to give 1,3-dioxolane compounds, from which the desired alkyl glyceryl ethers were obtained in high quantities. 1,3-Dioxolane (ketal) compounds based on acetone were used in the enzymatic preparation of monoglyceride on an industrial scale. On the basis of these protecting groups, we extended our studies concerning both the preparations and properties of novel polyol ether compounds, beginning with alkyl glycidyl ethers. Another typical property of surfactants containing 1,3-dioxolane units and acetal is degradability under acidic conditions. Several types of destructible/cleavable surfactants based on polyols, such as carbohydrates and polyethyleneglycol, were prepared. As for natural products containing polyol skeletons, much attention has been paid to their molecular design, in which protecting groups such as 1,3-dioxolane compounds or allyl ether have contributed to synthetic strategies.     

Applications of phase-transfer catalytic reactions to fatty acids and their derivatives: Present state and future potential

Phase-transfer catalysts (PTC), which accelerate reactions between liquid(organic)-liquid(water) and liquidsolid heterogeneous states, have been investigated and developed. Several processes with PTC have succeeded in industrial processes involving fatty acids and their derivatives. For example, preparation of fatty alkyl glycidyl ethers, from which fatty alkyl glyceryl ethers and their derivatives can be obtained, has been carried out with PTC. However, some problems remain to be solved. For example, preparation of the fatty alkyl glycidyl ether by a PTC reaction was considered, but typical problems to be solved included: (i) how to reuse or recover the catalysts; (ii) how to control the heterogeneous reaction without obstacles to produce useful chemical materials; (iii) how to satisfy the environmental requirements for the catalysts; and (iv) are there more effective catalysts? We address these problems based on our own experiences with phase-transfer catalytic Williamson ether syntheses of fatty alkyl glycidyl ethers. Moreover, we describe recent developments in phase-transfer catalytic reactions related to oleochemistry, such as transition metal-catalyzed reactions of long-chain olefins in liquid(organic)-liquid(water) or liquid-solid heterogeneous states. Based on these results, we have considered the potential of PTC as a synthetic tool in oleochemistry.     

Newer synthetic approaches to surfactants, lipids, and related compounds based on C-3 building blocks: Recent advances related to fatty chemistry

Many lipids derived from natural sources are based on the glycerin molecule. Synthetically alkyl glycidyl ether can be used as a C-3 building block for lipid molecules as well as alkyl glyceryl ether. Several glycidyl and glyceryl ethers have been studied as C-3 synthetic building blocks for lipids used in surfactants/emulsifiers, cosmetics, or toiletries. From an environmental viewpoint, several surfactants and detergents have been modified by using epichlorohydrin or glycerides as C-3 building blocks to have higher performance or biodegradability. Recently, complex lipid molecules having special bioactivities have attracted attention among chemists. Glycidyl ether would be expected to be one of the synthetic building blocks for such complex lipids.     

Self-assembly of compounds based on a glycerin skeleton as C-3 building block. Part II

Part I reviewed the properties of alkyl glyceryl ethers and their derivatives in forming self-assemblies such as liquid crystals. Part II covers strategies for the synthesis of several types of artificial ether lipids with a glycerin backbone, such as dicephalic surfactants, gemini surfactants, calamitic bola-amphiphiles, dendrimers, and membrane components of archaebacteria, which have been reported to constitute unique self-assemblies useful as materials for future nanochemistry.     

Epoxy resins based on resorcinol and its derivatives

Schemes are presented for the synthesis of epoxy oligomers based on resorcinol and its derivatives. The properties of furfurylresorcinol glycidyl ethers (UP-63 resin), oligomeric glycidyl ethers of glycerol dihydroxydiphenyl ether (UP-67 resin), diglycidyl ether of ethylene glycol dihydroxydiphenyl ether (UP-622 resin), and oligomeric glycidyl ether of pentaerythritol and resorcinol (UP-635 resin) are considered. These resins are shown to be substantially advantageous compared to standard bisphenol A-based epoxy oligomers. Materials possessing higher thermal stability and adhesion are developed on their basis.     

Self-assembly of compounds based on a glycerin skeleton as a C-3 building block. Part I

Biological structures from proteins through viruses to cellular organelles with dimensions of 1 to 100 nm require molecular self-assembly and self-organization to form nanostructures. In contrast to covalent bonding, noncovalent interactions such as hydrogen bonding and hydrophobic association involve lower bond energies (2–20 kcal/mol) to attain the mobility and fluidity properties of biological structures. Noncovalent interactions are also well-known with amphiphilic molecules bearing both hydrophilic head groups and hydrophobic groups and are responsible for the formation of several types of self-assemblies such as micelles, liquid crystals, and lipid bilayers. As typical amphiphiles with a glycerin skeleton as a C-3 building block, alkyl glyceryl ethers and their derivatives have been of interest since they show unique self-assembly structures such as liquid crystals with hitherto unknown character.     

Glyceryl ethers in insects: Biosynthesis of ethanolamine phosphoglycerides containing alkyl and alk-1-enyl glyceryl ether linkages

When¹⁴C-labeled acetate, fatty acids or fatty alcohols were injected into or fed to the tobacco budworm, acyl, alkyl and alk-1-enyl moieties of the phospholipids incorporated radioactivity. Fatty acids were the principal precursor in acyl bond formation and fatty alcohols in the synthesis of alkyl and alk-1-enyl glyceryl ethers. Detailed analysis of the etherlinked phosphoglycerides revealed that most of the radioactivity was in the ethanolamine phosphoglycerides, and very little¹⁴C was found in the choline phosphoglycerides. In experiments of a short duration, the alkyl glyceryl ethers incorporated more radioactivity than the alk-1-enyl glyceryl ethers. The reverse was found with long term experiments, when the alk-1-enyl ethers had higher radioactivity. In addition to demonstrating the synthesis of ether-linked ethanolamine phosphoglycerides, the data suggested that fatty alcohols and acids were interconverted by insects and that the alk-1-enyl ethers were derived from the alkyl ethers. Presented at the AOCS Meeting, Houston, May 1971. The following abbreviations and terminology will be used: PE, PC, PI and PS for the generic terms ethanolamine, choline, inositol and serine phosphoglycerides, respectfully. Alkyl glyceryl ether for 1-alkyl-2-acyl-sn-glycerol-3-phosphoryl-, and alk-1-enyl glyceryl ether for 1-alk-1′-enyl-2-acyl-sn-glycerol-3-phosphoryl-(commonly called plasmalogen). These are adapted from the tentative rules published inJ. Lipid Res. 8:522–528 (1967).     

Studies on the preparation and analysis of glyceryl ether derivatives and the isolation and reductive ozonolysis of unsaturated glyceryl ethers

Glyceryl ethers were identified and quantified by the GLC analysis of their alkyl iodide (special conditions described), acetonide and allyl alkyl ether derivatives. The acetoxy-mercuri-methoxy derivatives of unsaturated glyceryl ether swere separated from saturated glyceryl ethers by TLC and the fractions were analyzed as alkyl iodides. Monoiodides from saturated glyceryl ethers and diiodides from unsaturated glyceryl ethers were also separated by TLC and then analyzed. Allyl alkyl ethers had small retention volumes and these derivatives were separated into pure fractions by preparative GLC. Ozonides were reduced either to alcohols with lithium aluminum hydrodie or to aldehydes with dimethyl sulfide. The alcohols were converted to mono- and diiodides which were separated by TLC and analyzed by GLC. The recovery of n-C₆ and n-C₇ monoiodides was not quantitative. Diiodides and aldehydes were both identified and quantified by GLC. Ozonolysis data suggest that the 16∶1 glyceryl ethers from dogfish liver oil contain 7,8 and 9,10 isomers and the 18∶1 glyceryl ethers contain 9,10 and 11,12 isomers. Presented in part at the AOCS Meeting, Philadelphia, October 1966.     

Metabolism of alkyl glyceryl ethers in the rat

The metabolism of¹⁴C- and³H-labeled alkyl glyceryl ethers after intraperitoneal injections was examined in the liver and intestine of the rat. Additionally, in vitro experiments were conducted with intestinal homogenates and intetinal contents. From these investigations it was concluded that the liver and the intestine metabolize the alkyl glyceryl ethers very differently. Intestinal contents can alter α-batyl alcohol, as indicated by preliminary experiments, and intestinal cells contain enzyme systems which convert the alkyl glyceryl ethers to the mono- and di-acyl derivatives. Very little esterified glyceryl ethers were found in the liver lipids. The intestine contains an enzyme system which, although it has a greater specificity for chain length and for isomeric position of the ether than that of the liver system, does cleave the glyceryl ethers. From in vivo studies, of intestinal tissue it was concluded that all of the injected glyceryl ethers were converted intact the ethanolamine, serine, and choline alkyl glyceryl ether phospholipids; with the use of α-batyl alcohol, the phosphatidyl ethanolamine fraction, contained most of the labeled glyceryl ether phospholipid with β-batyl alcohol, α-chimyl, and β-chimyl alcohols, the phosphatidyl, choline fraction contained most of the labeled alkyl glyceryl ether phospholipid. No significant amount (<1%) of labeled alkyl glyceryl ether phospholipids was found in any of the rat-liver lipids. Predoctoral trainee supported by Public Health Service Training Grant 5TI-GM-404-04 from the National Institute of General Medical Sciences, National Institutes of Health. Work done in partial fulfillment of the Ph.D. in the Department of Biochemistry at the University of North Carolina.     

A perspective on the contribution of surfactants and lipids toward “Green Chemistry”: Present states and future potential

“Green Chemistry” has become a subject of increasing interest in recent years. The goal of efforts in this area is to develop environmentally friendly methods and processes to replace traditional reactions that use organic solvents, consume much energy, and generate undesirable by-products and/or waste. Utilization of renewable resources is an important component of Green Chemistry. Fats and oils represent one such resource. They can give rise to many types of surfactants and lipids that can modify properties of boundary phases between different phases. Thus, phase-transfer catalysts (PTC) based on surfactants or lipids have been reported to be useful in reactions such as oxidation and hydration reactions and in glycidyl ether formation. Another approach to satisfying Green Chemistry requirements is the recovery and recycling of reactants and/or substrates used. In the preparation of alkyl glyceryl ethers, the intermediate 1,3-dioxolane compounds prepared by addition of acetone to alkyl glycidyl ethers can be hydrolyzed to regenerate reusable acetone. Other examples of methodologies based on surfactants or lipids are summarized, and their potential contribution to Green Chemistry is discussed.     

Thermodynamic equilibrium analysis on the dehydration of glycerol with monohydric alcohols to alkyl glyceryl ethers

Under the conditions of the feed of 400 moles of alcohol + 100 moles of glycerol, 313–573 K and 0.1 MPa, based on Gibbs free energy global minimization, an improved genetic algorithm was used for the thermodynamic equilibrium analysis on the synthesis processes of alkyl glyceryl ethers, respectively, from methanol + glycerol, ethanol + glycerol, isobutanol + glycerol, and tert-butanol + glycerol. The columnar stacking charts and three-dimensional contour graphs were used to compare the effects of temperature, pressure, and the feed ratio to the equilibrium conversion, product selectivity, and equilibrium composition. The basic laws of the synthesis processes of alkyl glycerol ethers in homogeneous and heterogeneous states were investigated in a wide temperature range. Through comparison, it was found that the isopropanol + glycerol system is easier to convert into alkyl glycerol ethers, followed by the ethanol + glycerol system. The methanol + glycerol system and tert-butanol + glycerol system are greatly affected by pressure and temperature, and their conversions and selectivities are relatively low.     

Star-Shaped Poly(furfuryl glycidyl ether)-Block-Poly(glyceryl glycerol ether) as an Efficient Agent for the Enhancement of Nifuratel Solubility and for the Formation of Injectable and Self-Healable Hydrogel Platforms for the Gynaecological Therapies

In this paper, we present novel well-defined unimolecular micelles constructed a on poly(furfuryl glycidyl ether) core and highly hydrophilic poly(glyceryl glycerol ether) shell, PFGE-b-PGGE. The copolymer was synthesized via anionic ring-opening polymerization of furfuryl glycidyl ether and (1,2-isopropylidene glyceryl) glycidyl ether, respectively. MTT assay revealed that the copolymer is non-cytotoxic against human cervical cancer endothelial (HeLa) cells. The copolymer thanks to furan moieties in its core is capable of encapsulation of nifuratel, a hydrophobic nitrofuran derivative, which is a drug applied in the gynaecology therapies that shows a broad antimicroorganism spectrum. The study shows high loading capacity of the copolymer, i.e., 146 mg of nifuratel per 1 g of copolymer. The load unimolecular micelles were characterized using DLS and TEM microscopy and compared with the reference glyceryl glycerol ether homopolymer sample. The presence of numerous 1,2-diol moieties in the shell of PFGE-b-PGG macromolecules enabled the formation of reversible cross-links with 2-acrylamidephenylboronic acid-based polyacrylamide. The obtained hydrogels were both injectable and self-healable, which was confirmed with a rheological study.     

寡甘醇单烷基醚的合成和性能

以寡甘醇和卤代烷为原料,利用相转移催化Ｗｉｌｌｉａｍｓｏｎ法合成了１２种寡甘醇单烷基醚,均获得较高产率。讨论了寡甘醇单醚合成的反应历程,并对其物理常数、水溶液的表面张力、起泡性能、临界胶束浓度进行了测试和分析。     

Enol esters XVI: Enol ethers in synthesis

The synthesis of isopropenyl octadecyl ether is reported. This compound is a useful reagent for the synthesis of wax esters by reaction with long chain fatty acids, and of symmetrical or unsymmetrical ethers via reaction with long chain alcohols. The long chain alkyl isopropenyl ether is more sensitive to hydrolysis than the corresponding enol ester and forms successively the ketal 2,2-dioctadecyloxypropane, and octadecanol and acetone. Glycerol reacts with propyne yielding glycerol acetonide, glycerol acetonide isopropenyl ether and diglycerol bisacetonide. New crystalline derivatives of diglycerol are described, useful for the characterization of that substance. E. Market. Nutr. Res. Div., ARS, USDA.     

高活性环氧树脂增韧稀释剂的合成及应用

以腰果酚、壬基酚为原料制备了环氧树脂活性稀释剂腰果酚基缩水甘油醚(CGE)和壬基苯基缩水甘油醚(NGE),对其结构及其与E51共混体系的固化物结构进行了红外光谱表征。考察了不同合成方法对产物性能的影响,CGE及NGE对环氧树脂的稀释作用以及其含量对固化物的力学性能的影响。结果表明,CGE与NGE对环氧树脂具有显著的稀释作用,质量分数为20%时尤为明显。CGE及NGE均参与了固化反应。E51/NGE共混体系的力学性能保持较好,当E51与NGE质量比为80∶20时,其固化物拉伸强度、弯曲强度、弯曲模量保持率较高。该合成方法原料价格低廉,产品具有良好的增韧稀释效果,可用于无溶剂涂料的配制。     

A convenient synthesis of long-chain 1-O-Alkyl glyceryl ethers

A convenient and economical procedure for synthesis of long-chain 1-O-alkyl glyceryl ethers (V) is described. Alkyl glycidyl ethers (II) which were derived from the reaction of alcohols (I) with epichlorohydrin using a phase transfer catalyst were first converted into the corresponding dioxolanes (III) or 1-O-alkyl-2,3-di-O-acetylglycerols (IV). Subsequent hydrolysis of the resultant products provided 1-O-alkyl glyceryl ethers (V) in high yields.     

腰果酚缩水甘油醚的工艺技术研究

以腰果酚和环氧氯丙烷为主要原料,在催化剂苄基三乙基氯化铵的催化下合成了腰果酚缩水甘油醚。考察了反应条件对环氧值的影响,通过正交试验和单因素试验确定了合成腰果酚缩水甘油醚的适宜工艺条件为:n(腰果酚)∶n(环氧氯丙烷)∶n(氢氧化钠)=1∶5∶1.2,醚化温度为80℃,醚化时间为4 h,闭环温度为60℃,闭环时间为3 h,催化剂为腰果酚质量的2%,腰果酚缩水甘油醚的环氧值高达到0.279并且收率达到85.6%。     

Glyceryl ether,wax ester and triglyceride composition of the mouse preputial gland

Major lipid classes of the preputial gland of the mouse have been identified as wax ester, neutral plasmalogen, glyceryl ether diester and triglyceride. The chain lengths and degree of unsaturation in the aliphatic moieties of the alk-1-enyl and alkyl glyceryl ethers are similar to those of the fatty alcohols of the wax ester fraction. This lends support to the theory that long chain fatty alcohols can be direct precursors of the aliphatic chains of glyceryl ethers. The striking qualitative, as well as quantitative, similarities between the alkyl and alk-1-enyl moieties of the glyceryl ethers in the neutral lipid fraction suggest that they share a common pathway of biosynthesis or are interconvertible. Neutral plasmalogens and glyceryl ether diesters contain significant amounts of odd-numbered and branched fatty acids, unlike the fatty acids of the triglycerides; therefore, the biosynthesis of neutral plasmalogens and glyceryl ether diesters may not be related to the biosynthesis of triglycerides. Presented at the AOCS Meeting, Chicago, October, 1967. Taken from a dissertation submitted to Tulane University in partial fulfillment of the requirement for the degree of Doctor of Philosophy by Gail Sansone.     

相转移催化法合成十二烷基缩水甘油醚

以十二醇和二氯丙醇为原料,用相转移催化剂直接合成了十二烷基缩水甘油醚。考察了催化剂种类、原料摩尔比、反应时间和反应温度对十二烷基缩水甘油醚收率的影响。结果表明,以四丁基溴化铵为催化剂,甲苯为溶剂,n(十二醇)∶n(二氯丙醇)=1∶1.60,反应温度50℃,反应时间4 h,十二烷基缩水甘油醚收率可达73.2%。用IR、1HNMR对产物结构进行了表征,采用测定产品环氧值的方法来计算十二烷基缩水甘油醚的收率。