Fatty hydroxy-substituted

A simple approach for lipidation of peptides with di-fatty acid substituted glycerol moieties is based on the use of glyceric acid.119" For this purpose (2i )-glyceric acid is esterified at the two hydroxy groups with fatty acid acyl chlorides and the resulting lipophilic synthon (18) is used directly as an active ester, e.g. Pfp ester, to acylate selected amino groups of peptides, or is used to acylate suitably functionalized spacers. 

Lactones, due to their ring structure, are easily opened with nucleophiles (35) to yield the corresponding 5-hydroxy substituted derivatives (Scheme 12). Table 1 lists the relative rates of derivitization of meadowfoam fatty acids, y-lactones, and 8-lactones in reactions with alcohols and amines. All of the relative rates were compared with the rate of esterification for meadowfoam fatty acids (FA). These data clearly demonstrate the enhanced reactivity of the 8-lactone structure with respect to fatty acids and even its analog, y-lactone. 

Any amount of a 10 carbon hydroxy-substituted fatty acid moiety is cell associated and synthesized de novo,... 

Polymers from hydroxy-substituted fatty acids or esters, derived from fats and oils and bifunctional compounds, have been reported [277]. The fat- and glyceridic oil-derived monomers used represent an inexpensive and readily obtainable monomer source for the preparation of condensation polymers from hydroxy- or amino-substituted fatty acids (e.g. 12-hydroxystearic acid) with difunctional compounds (e.g. diamines, polyamines, amino alcohols, diols, polyols, diacid chlorides, diisocyanates, phosgene, etc.). 

The term naphthenic acid, as commonly used in the petroleum industry, refers collectively to all of the carboxyUc acids present in cmde oil. Naphthenic acids [1338-24-5] are classified as monobasic carboxyUc acids of the general formula RCOOH, where R represents the naphthene moiety consisting of cyclopentane and cyclohexane derivatives. Naphthenic acids are composed predorninandy of aLkyl-substituted cycloaUphatic carboxyUc acids, with smaller amounts of acycHc aUphatic (paraffinic or fatty) acids. Aromatic, olefinic, hydroxy, and dibasic acids are considered to be minor components. Commercial naphthenic acids also contain varying amounts of unsaponifiable hydrocarbons, phenoHc compounds, sulfur compounds, and water. The complex mixture of acids is derived from straight-mn distillates of petroleum, mosdy from kerosene and diesel fractions (see Petroleum). 

As mentioned in the introduction, 3-hydroxy fatty acids with functional groups can also be incorporated in poly(3HAMCL). Table 2 illustrates this with many examples of alkenes, 3-hydroxyalkenoic acids, and substituted 3-hy-droxyalkanoic acids that are readily integrated in poly(3HAMCL). Long chain fatty acids have also been used successfully as substrates for poly(3HAMCL) production. De Waard et al. [44] used oleic acid and linoleic acid to produce... 

FIGURE 3-7 Pathways for the interconversion of brain fatty acids. Palmitic acid (16 0) is the main end product of brain fatty acid synthesis. It may then be elongated, desaturated, and/or P-oxidized to form different long chain fatty acids. The monoenes (18 1 A7, 18 1 A9, 24 1 A15) are the main unsaturated fatty acids formed de novo by A9 desaturation and chain elongation. As shown, the very long chain fatty acids are a-oxidized to form a-hydroxy and odd numbered fatty acids. The polyunsaturated fatty acids are formed mainly from exogenous dietary fatty acids, such as linoleic (18 2, n-6) and a-linoleic (18 2, n-3) acids by chain elongation and desaturation at A5 and A6, as shown. A A4 desaturase has also been proposed, but its existence has been questioned. Instead, it has been shown that unsaturation at the A4 position is effected by retroconversion i.e. A6 unsaturation in the endoplasmic reticulum, followed by one cycle of P-oxidation (-C2) in peroxisomes [11], This is illustrated in the biosynthesis of DHA (22 6, n-3) above. In severe essential fatty acid deficiency, the abnormal polyenes, such as 20 3, n-9 are also synthesized de novo to substitute for the normal polyunsaturated acids. 

Desaturation of alkyl groups. This novel reaction, which converts a saturated alkyl compound into a substituted alkene and is catalyzed by cytochromes P-450, has been described for the antiepileptic drug, valproic acid (VPA) (2-n-propyl-4-pentanoic acid) (Fig. 4.29). The mechanism proposed involves formation of a carbon-centered free radical, which may form either a hydroxy la ted product (alcohol) or dehydrogenate to the unsaturated compound. The cytochrome P-450-mediated metabolism yields 4-ene-VPA (2-n-propyl-4pentenoic acid), which is oxidized by the mitochondrial p-oxidation enzymes to 2,4-diene-VPA (2-n-propyl-2, 4-pentadienoic acid). This metabolite or its Co A ester irreversibly inhibits enzymes of the p-oxidation system, destroys cytochrome P-450, and may be involved in the hepatotoxicity of the drug. Further metabolism may occur to give 3-keto-4-ene-VPA (2-n-propyl-3-oxo-4-pentenoic acid), which inhibits the enzyme 3-ketoacyl-CoA thiolase, the terminal enzyme of the fatty acid oxidation system. 

Analyses of the lipid A components show a general similarity of composition between the lipid A material isolated from each of the seven immunotypes. All contain a B-D-(l->6)-linked 2-amino-2-deoxy-D-glucose disaccharide (17,18), substituted at both amino groups and at most of the hydroxyI—groups by 3-hydroxy fatty acyl chains, and phosphate ester groups are present at 0-1 and 0-4. ... 

Additionally, Rivkin and co-workers synthesized a variety of 4-hydroxy-3-phenylquinolin-2-(l//)-ones under solvent free microwave conditions using an activated arylmalonate <06TL2395>. Reacting the desired substituted aniline with di-(2,4,6-trichlorophenyl)-2-phenyl-malonate at 250 °C with microwave irradiation for 15 min resulted in a variety of 4-hydroxy-3-phenylquinolin-2-(l//)-ones in good yields. They also demonstrated the utility of this method in the synthesis of type I fatty acid synthase inhibitors <06BMCL4620>. Kumar et al. have reported a variation of the Friedlander quinoline synthesis. They highlight the use of CeClj THjO as a reusable catalyst in the reaction of 2-... 

---