Cyclopentenyl fatty acids

In this category, fatty acids with a terminal cyclopentenyl ring are best known (Sebedio and Grandgirard, 1989). There are three main types hydnocarpic (ll-cyclopent-2-enyl-undecanoic) acid (structure IVa, Fig. 5.1), chaulmoogric (13-cyclopent-2-enyl-tridecanoic) acid (structure IVb) and gorlic (13-cyclopent-2-enyl-tridec-6-enoic) acid (structure IVc) and its positional isomers (13-cyclopent-2-enyl-tridec-4-enoate and 13-cyclopent-2-enyl-tridec-9-enoate). They usually occur in varying proportions as major components (up to 90% of total fatty acids) in seed oils along with smaller amounts of saturated, oleic and linoleic acids. 

As methyl esters, GC separation from other fatty acids can be achieved on polar capillary columns (Fig. 5.3 Christie, Brechany and Shukla, 1989) and would probably be adequate on non-polar columns, as this is possible for dimethyloxazoline (DMOX) derivatives (Zhang et al, 1989). If necessary, prior isolation of cyclic monoenoic and dienoic fractions, separated from straight-chain saturates, monoenes and dienes, may be obtained by means of silver-ion HPLC (Christie, Brechany and Shukla, 1989). In this way, minor components were concentrated for subsequent GC-MS analysis as the pico-linyl (3-hydroxymethylpyridinyl) esters, and the possibility of inadequate resolution from straight-chain esters on non-polar columns, necessary for eluting these relatively involatile derivatives, was avoided. Presumably the use of modern high-temperature polar phases for GC-MS would eliminate possible resolution problems with picolinyl esters. 

A terminal cyclopentenyl group is evident in the mass spectra of the methyl esters. For example, for methyl hydnocarpate the base peak at m/z (mass per 

In a study of DMOX derivatives of cyclopentenyl acids (Zhang et al, 1989), the possible m/z 67 ion was not recorded and, in contrast to the spectra of picolinyl esters, the gap between the molecular and [M-67] ions was not always obvious (e.g. from m/z 331 to 264 for the 4-isomer Fig. 5.5). However, it appears that the combination of gaps of 12 amu between [M-67] and [M-55] m/z 276) and [M-43] m/z 288) ions are characteristic for DMOX derivatives of cyclopentenyl acids. For the 4-iso-mer, a gap of 26 amu between m/z 126 and 152 together with an unusual odd-number ion at m/z 139 located the double bond position. 

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Chaulmoogric and hydnocarpic acids (Figure 3.15) are cyclopentenyl fatty acids found in chaul-moogra oil expressed from seeds of Hydnocar-pus wightiana (Flacourtiaceae). These acids are known to arise by malonate chain extension of the... 

Cramer, U. and F. Spener, Biosynthesis of cyclopentenyl fatty acids, Biochim. Biophys. Acta, 450, 261-265 (1976). 

Figure 5.4 Mass spectrum (70 eV) of a picolinyl ester derivative of 13-cyclopent-2-enyl-tridec-6-enoic (gorlic) acid. M" = molecular ion. Redrawn from Christie, W. W., Brechany, E. Y. and Shukla, V. K. S., Analysis of seed oils containing cyclopentenyl fatty acids by combined chromatographic procedures,... 

Figure 5.5 Mass spectrum (70 eV) of a dimethyloxazoline derivative of 13-cyclopent-2-enyl-tridec-4-enoate. M = molecular ion. Redrawn from Zhang, J. Y. Wang, H. Y., Yu, Q. T. et al. The structures of cyclopentenyl fatty acids in the seed oils of Flacourtiaceae species by GC-MS of their 4,4-dimethyloxazo-...

Shukla, V. K. S. and Spener, F. (1985) High-performance liquid chromatography of triglycerides of Flacourtiaceae seed oils containing cyclopentenyl fatty acids (chaulmoogric oils). 

Cramer and Spener, 1977). They have been detected as minor constituents in leaves and cell cultures of these plants (Spener and Mangold, 1975 Spener et al., 1974) and also in various tissues and organs of Flacourtieae, not heretofore known as sources of cyclopentenyl fatty acids (Rehfeldt et al., 1980). 

It was considered possible that cyclopentenyl fatty acids might be formed by oxidative ring closure of polyunsaturated straight-chain fatty acids... 

Fig. 4. Structures of cyclopentenyl fatty acids. Homologues of chaulmoogric acid, CsHt—(CH,)n—COOH, are, withn = 0, 2, 4, 6, 8, 10, 14, aleprolic, alepraic, aleprestic, alepry-lic, alepric, hydnocarpic, and hormelic acids, respectively. A homologue of gorlic acid is onco-bic acid, 15-(2 -cyclopentenyl)-8-pentadecenoic acid.

Spener and Mangold, 1974) in a manner similar to the biosynthesis of prostaglandins (Lands et al., 1977). However, polyunsaturated fatty acids that would undergo such a reaction have not been found in various tissues and cell cultures of Flacourtiaceae (Spener and Mangold, 1974, 1975 Spener et al., 1974). Alternatively, the occurrence of an homologous series of even-numbered cyclopentenyl fatty acids implied a biosynthetic scheme analogous to that for the common fatty acids. 

The pivotal role of aleprolic acid (cyclopentenylcarboxylic acid) as primer in the biosynthesis of cyclopentenyl fatty acids was examined in a variety of tissues. In seeds of anthelminthica and C. echinata [l- C]aleprolic acid was almost exclusively incorporated into cyclopentenyl fatty acids, and in cells of I. polycarpa suspension cultures at a level of well over 60% (Cramer and Spener, 1976 Buchholz and Spener, 1980). In the cell cultures used, where endogenous cyclopentenyl fatty acids occurred only at a minor level, the substrate was taken up and activated for both anabolic and catabolic reactions. The acetate thus formed was refunneled and used for the de novo synthesis predominantly of straight-chain fatty acids (Buchholz and Spener, 1980). 

Administration of [l- C]aleprolic acid to chopped leaves of H. anthelminthica and C. echinata showed that most of the substrate was also catabolized. When subcellular fractions devoted mainly to catabolic events were removed, [l- C]aleprolic acid supplied to chloroplasts primed the synthesis of cyclopentenyl fatty acids only (Rehfeldt et al., 1980). 

With respect to fatty acid biosynthesis, plant cell suspension cultures resemble cells in green leaves of intact plants. In leaves of Flacourtiaceae, straight-chain and cyclic fatty acid biosynthesis is located in chloroplasts. The locus of this biosynthetic process in seeds, the main cyclopentenyl fatty acid-producing organ, is not known the results obtained with cultured cells may indicate localization in the cytosol. However, the model function of cell cultures should be considered with caution. 

The introduction of a double bond into the aliphatic chain, i.e., the desaturation of monounsaturated cyclopentenyl fatty acids, is oxygen-dependent, and its mechanism resembles that for straight-chain fatty acids. After administration of [l- C]aleprolic acid to H. anthelminthica seeds, as well as to C. vulgaris, the ratio of mono- to diunsaturated cyclopentenyl fatty acids synthesized greatly increased under anaerobic conditions (Spener, 1975). 

It is interesting that the C. vulgaris system produced isomers of diunsaturated cyclopentenyl fatty acids identical to those isolated from Flacourtia-... 

Chaulmoogra oils, individual cyclopentenyl fatty acids, and their derivatives have been used for centuries in the treatment of leprosy. Yet, satisfactory results have not been achieved, even in modem times (Schlossberger, 1938). However, activity against Mycobacterium leprae has been reported for the sodium salts of hydnocarpic and chaulmoogric acids (Levy, 1975). 

The main occurrence of cyclopentenyl fatty acids in seeds of Flacourtia-ceae suggests a function as an eneigy reserve to be utilized during germination. The degradability of these alicyclic acids by endogenous enzymes can be deduced from indirect evidence. In the course of jS-oxidation, aleprolic acid must be formed as an intermediate. It has been shown that exogenously added [l- C]aleprolic acid is readily catabolized (Cramer and Spener, 1976). 

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