Phytol Derivatives Research Articles

Lipophilic constituents from aerial and root parts of Mercurialis perennis L.

Dog's mercury (Mercurialis perennis L.) is a perennial herb used in remedies for medicinal purposes. The plant is supposed to contain potentially active substances but its constituents have only been rarely studied. Detailed studies on the phytochemical composition are of great interest to broaden the knowledge on the chemotaxonomy and pharmacognosy of M. perennis. Chloroform and hexane extracts from roots and aerial parts were investigated using GC/MS and LC/MS. The whole plant exhihited a broad spectrum of structurally diverse constituents, mainly alkaloids, terpenes, sterols and simple aromatic compounds. Closer inspection of the piperidine alkaloid hermidin revealed its inherent instability towards air oxygen. To obtain quantitative data on these alkaloids the synthesis of the more stable reference compound 4-methoxy-1-methylpyridine-2,6(1H,3H)-dione (MMPD) was required. In this study, MMPD was detected for the first time as a genuine compound in Mercurialis. Hermidine quinone and hermidin dimers originating from hermidin via a free anionic radical reaction were also confirmed by GC/MS. Moreover, volatile compounds such as benzylalcohol, 2-phenylethanol, 4-methoxy- and 3,4-dimethoxyphenol, (-)-cis- and (+)-trans-myrtanol, (-)-cis-myrtanal as well as squalene were predominantely present in Mercurialis roots. In contrast, aerial parts mainly contained phytol derivatives, sterols and tocopherols. By changing solvent polarity, lipid and wax-containing fractions were obtained. LC/MS-studies on hexane extracts showed the presence of several mixed triglycerides constituted by linolenic, linoleic, oleic, stearic and palmitic acids, as well as lutein, carotenes and pheophytins. The phytochemical data presented complement our knowledge on the rarely studied plant M. perennis and may broaden its use in future phytotherapy.

Aphrodisiac Pheromones from the Wings of the Small Cabbage White and Large Cabbage White Butterflies, Pieris rapae and Pieris brassicae

The small and large cabbage butterflies, Pieris rapae and P. brassicae, are found worldwide and are of considerable economic importance. The composition of the male scent-producing organs present on the wings was investigated. More than 120 components were identified, but only a small portion proved to be male specific. Major components were the known beetle pheromone ferrulactone (1) in P. rapae and its previously unknown larger analogue, brassicalactone (2), in P. brassicae. The latter carries an additional isoprene unit and is closely related to 1. Other components present in larger amounts on male relative to female wings were hexahydrofarnesylacetone (18) and phytol (23). Brassicalactone (2) was fully characterized by synthesis of its various diastereomers by using ring-closing metathesis. A similar approach to ferrulactone (1) failed, presumably because of its smaller ring size. Instead, this compound was synthesized by using a modified literature procedure. The biological activity of the compounds in the extract was tested by coupled gas chromatographic-electroantennographic (GC-EAD) analysis, which showed that both macrolides and the other major components of the wings can be detected by the antennae of the conspecific female butterflies. Other detectable compounds included several alkanes, which are typical constituents of the butterfly cuticula, derivatives of phytol (23) and long-chain secondary alcohols. Finally, bioassays with males showed that the mixture of 1 (P. rapae) or 2 (P. brassicae) together with 18 and 23 applied to freshly eclosed males increased mating success compared to untreated males. Therefore, the two macrolides 1 and 2 are aphrodisiac pheromone components of male small and large cabbage white butterflies, respectively.

Novel phytol-based adjuvants in vaccine formulations: Evaluation of safety and efficacy in induction and persistence of specific immune responses (41.64)

Abstract Adjuvants function as "immunologists' dirty tricks" for enhancement of immune response. However, no two adjuvants work in a similar fashion. Adjuvant efficacy depends on how they influence microenvironment, antigen presentation and retention of immunogens. We are developing water-in-oil emulsion-type adjuvants from phytol (J Immune Based Ther Vaccines 2006, 5:4; ibid 2007; 5: 3). Phytol is a diterpene present in chlorophylls, alpha-tocopherols etc. Phytol derivatives we developed are hydrogenated/nitrated and glycosylated products (US patent pending). Our previous study showed that one phytol derivative PHIS-01(hydrogenated) is an excellent non-toxic adjuvant. In this study, we investigated the safety and efficacy of two other phytol compounds, PHIS-02 and PHIS-03 relative to PHIS-01 and other adjuvants. Using phthalate- keyhole limpet hemocyanin (KLH) conjugate as the immunogen emulsified with these adjuvants, we assessed titer, specificity, and isotypic profiles of anti-phthalate antibodies induced. In addition, we studied their effects on cellular immunity such as T cell proliferation and cytokine production. Preliminary results show that (1) phytol adjuvants significantly augment antibody response of isotypes IgG1 and IgG2a, (2) promote effective T cell proliferation, and (3) exhibit low toxicity with no adverse autoimmune anti-DNA response. We also observed that these adjuvants exert apoptotic/necrotic effects on mouse lymphoma cells 2C3 and A20 in a concentration-dependent manner.

Shift in birch leaf metabolome and carbon allocation during long‐term open‐field ozone exposure

AbstractCurrent and future ozone concentrations have the potential to reduce plant growth and increase carbon demand for defence and repair processes, which may result in reduced carbon sink strength of forest trees in long‐term. Still, there is limited understanding regarding the alterations in plant metabolism and variation in ozone tolerance among tree species and genotypes. Therefore, this paper aims to study changes in birch leaf metabolome due to long‐term realistic ozone stress and to relate these shifts in the metabolism with growth responses. Two European white birch (Betula pendula Roth) genotypes showing different ozone sensitivity were growing under 1.4–1.7 × ambient ozone in open‐field conditions in Central Finland. After seven growing seasons, the trees were analysed for changes in leaf metabolite profiling, based on 339 low molecular weight compounds (including phenolics, polar and lipophilic compounds, and pigments) and related whole‐tree growth responses. Genotype caused most of the variance of metabolite concentrations, while ozone concentration was the second principal component explaining the metabolome profiling. The main ozone caused changes included increases in quercetin‐phenolic compounds and compounds related to leaf cuticular wax layer, whereas several compounds related to carbohydrate metabolism and function of chloroplast membranes and pigments (such as chlorophyll‐related phytol derivatives) were decreasing. Some candidate compounds such as surface wax‐related squalene, 1‐dotriacontanol, and dotriacontane, providing growth‐related tolerance against ozone were demonstrated. This study indicated that current growth‐based ozone risk assessment methods are inadequate, because they ignore ecophysiological impacts due to alterations in leaf chemistry.

A new route to Vitamin E key-intermediates by olefin cross-metathesis

The ruthenium-catalyzed olefin cross-metathesis has been successfully applied to the synthesis of derivatives of phytyltrimethylhydroquinone. These products, containing a trisubstituted olefinic double bond, are useful intermediates for an alternative route to α-tocopheryl acetate (Vitamin E acetate). Using the second generation Grubbs’ catalyst RuCl 2(C 21H 26N 2)(CHPh)PCy 3 (Cy = cyclohexyl) and Hoveyda–Grubbs’ catalyst RuCl 2(C 21H 26N 2){CH-C 6H 4(O-iPr)-2}, the reactions were performed with various C-allylated and O-allylated derivatives of trimethylhydroquinone-1-acetate as substrates. 2,6,10,14-Tetramethylpentadec-1-ene and derivatives of phytol were employed as olefin partners for the cross-metathesis reactions. The Vitamin E precursors could be prepared in up to 83% isolated yields as mixtures of E and Z stereoisomers.

Fern Constituents: Dryocrassy Formate, Sitostanyl Formate and 12α‐Hydroxyfern‐9(11)‐ene from Cyathea podophylla.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Fern constituents: dryocrassy formate, sitostanyl formate and 12alpha-hydroxyfern-9(11)-ene from Cyathea podophylla.

Dryocrassyl formate, sitostanyl formate, and 12alpha-hydroxyfern-9(11)-ene were isolated from the fresh fronds of Cyathea podophylla. Their structures were elucidated by spectroscopic techniques and synthesis. Ten known triterpenoids, three derivatives of phytol, a stanol, and beta-tocopherol were also identified from this fern.

Phytanic acid, but not pristanic acid, mediates the positive effects of phytol derivatives on brown adipocyte differentiation

The phytol derivatives phytanic acid and pristanic acid may activate nuclear hormone receptors and influence gene expression and cell differentiation. Phytanic acid induces brown adipocyte differentiation. It was determined that brown fat and brown adipocytes are sites of high gene expression of phytanoyl-CoA hydroxylase, the enzyme required for initiation of peroxisomal α-oxidation of phytanic acid. However, the effects of phytanic acid were not mediated by its α-oxidation product pristanic acid, which did not promote brown adipocyte differentiation or stimulate transcription of the uncoupling protein-1 gene. Moreover, acute cold exposure of mice caused a dramatic mobilization of the phytanic acid stores in brown adipose tissue thus suggesting that a high local exposure to phytanic acid in brown fat may contribute to signalling adaptive changes in the tissue in response to thermogenic activation.

Limonoids and phytol derivatives from Cedrela sinensis

Two new compounds, cedrellin (1) and 2,6,10,15-phytatetraene-14-ol (2), together with five known compounds, 7α-obacunyl acetate, 6-acetoxyobacunol acetate, 7α-acetoxydihydronomilin, 2,6,10-phytatriene-1,14,15-triol and phytol were isolated from leaves of Cedrela sinensis. Their structures were elucidated on the basis of combined one- and two-dimensional spectral techniques.

Shield Defense of a Larval Tortoise Beetle

Larvae of the folivorous tortoise beetle, Plagiometriona clavata, carry shields formed from feces and exuviae above their bodies. We used an ecologically relevant predatory ant, Formica subsericea, in a bioassay to determine if shields functioned as simple barriers, as previous studies indicated, or whether they were chemical defenses. Shields were necessary for larval survival; shield removal rendered larvae vulnerable. Shields produced by larvae reared on a substitute diet failed to provide protection. Solvent-leached shields also failed to deter ants, indicating the shield had a host-derived chemical component likely located in the feces, not in the exuviae. Solanum dulcamara, the larval host plant, contained free phytol, steroidal glycoalkaloids, and saponins. Shields contained partially deglycosylated metabolites of host steroidal glycoalkaloids and saponins, a suite of fatty acids, and derivatives of phytol, which together formed a deterrent barrier against ant attack. We compared the mobile shield of P. clavata to the stationary shield of another S. dulcamara-feeding leaf beetle, Lema trilinea. Both larval shield defenses were formed from a very similar array of host-derived compounds with deterrent properties. We concluded that convergent patterns of limited chemical transformation and selective incorporation of particular deterrent metabolites in shield defenses of two unrelated taxa represented responses to selection from invertebrate predators.

Mass-spectrometric analysis of phytol derivatives from the leaves ofPlatanus orientalis

Products of the oxidation, polymerization, and esterification of tocopherols and esters of phytol with aliphatic acids have been identified in fractions of an alcoholic extract of shed plane leaves by means of mass-spectrometric analysis.

Chemical Composition of the Essential Oil ofSenecio ambavilla(Bory) Pers. from Réunion Island

ABSTRACT Sixty-two compounds have been characterized by GC/MS and relative retention times in the essential oil of Senecio ambavilla (Bory) Pers. produced from plant material growing in Reunion (Indian Ocean). The oil was found to be rich in allo-aromadendrene (40%) and α-pinene (14%). While accounting numerically for approximatively third of the total number of compounds present in the oil, the monoterpene compounds contributed less than 23% of the oil content. On the other hand 70% of the oil was sesquiterpenoid in nature. In addition, long chain aldehydes, eremophilane, phytol (a diterpene alcohol) and indene derivatives were also identified as minor constituents.

Incorporation of sulphur into phytol derivatives during simulated early diagenesis

Elemental sulphur and unsaturated phytyl derivatives have been shown to react in the presence of trimethylamine at low temperature (45°C) to produce two C 20 isoprenoid thiophenes which have been reported previously in unconsolidated sediments. The type of reaction involved, which takes place under mild hydrous conditions with common sedimentary species, is, therefore, of significance for the formation of thiophenes during early diagenesis.

Changes in the Endogenous Pools of Tetraprenyl Diphosphates in Etiolated Oat Seedlings after Irradiation

The chlorophyll synthetase reaction (Rüdiger et al., 1980) was used as a probe to investigate the soluble and membrane-bound pools of phytyl diphosphate and geranylgeranyl diphosphate in etiolated seedlings of oat ( Avena sativa L.). Incubating increasing amounts of the soluble fractions of etiolated seedlings («supernatant») with a standard, irradiated etioplast membrane preparation, produced increasing amounts of esterified chlorophyll, mainly Chl GG , while incubation of the same membrane preparation with 3 H-geranylgeranyl diphosphate yielded labelled Chl GG and unlabelled Chl p . The Chl p was derived from a membrane-bound pool of phytol derivatives rather then by hydrogenation in vitro from Chl GG . Esterification of chlorophyllide, the ratio of applied substrates GGPP/PhyPP and the ratio of formed pigments Chl GG /Chl p are compared diagramatically (Fig. 2). The effect on the composition of the supernatants of etiolated seedlings of a short period of irradiation, followed by various dark periods, were also investigated. The soluble GGPP pool of etiolated seedlings was depleted by the irradiation but refilled in the subsequent dark period. Only a small soluble phytyl diphosphate pool was detected.

Stereoselektive Totalsynthese von natürlichem Phytol und Phytolderivaten und deren Verwendung zur Herstellung von natürlichem Vitamin K1

Steroselective Total Synthesis of Natural Phytol and Derivatives thereof; Use of these Compounds in the Synthesis of Natural Vitamin K1The Li2CuCl4‐catalyzed couplings of the easily accessible bifunctional C5 allylic acetates (E)‐18a and (E)‐18b with racemic hexahydrofarnesylmagnesium bromide ((3 RS/RS, 7 RS/SR)‐19a) proceed with high chemo‐ and stereoselectivity (≥98% (E)‐retention) to give the (2E, 7 RS/RS, 11 RS/SR)‐phytol derivatives 1a and 1b, respectively, in yields of 72–80% (Scheme 5). The same couplings performed with optically active hexahydrofarnesylmagnesium bromide (3 R, 7 R)‐19a yielded the (E)‐phytol derivatives of the natural series (7 R, 11R)‐1a and (7 R, 11 R)‐1b. Acid‐catalyzed hydrolysis of(2 E, 7 R, 11 R)‐1b gave natural phytol((2 E, 7 R, 11 R)‐1c) Friedel‐Crafts alkylation of ‘menadiol monobenzoate’ 11b with (2 E, 7 R, 11 R)‐1a or (2 E, 7 R, 11 R)‐1b gave the dihydrovitamine K1 derivative (2 E/Z, 7′ R, 11′R)‐12b ((E/Z)≈︁ 9:l). Conversion of configurationally pure (2 E, 7′ R, 11′ R)‐12b (yield 73%; obtained after chromatographic removal of the (Z)‐isomer) into natural vitamine K1 ((2 E,7′ R, 11′ R)‐2) was achieved in the usual way by saponification and oxidation with air.Some further investigations of the coupling reactions of bifunctional C5 allylic synthons with hexahydrofarnesylmagnesium bromide (3 RS/RS, 7 RS/SR)‐19a showed the outcome of these reactions to be critically dependent on the nature of the leaving group, the double‐bond geometry and the nature and concentration of the catalyst. Thus, the Li2CuCl4‐catalyzed couplings of (3 RS/RS,7 RS/SR)‐19a with the allylic halides 29a and 29c as well as with p‐toluenesulfonate 29b yielded besides the phytol derivatives 1a and 1b ‐ also the SN2′‐type products 30a and 30b (Scheme 8, Table 2); the same result was found for the coupling with the cis‐configurated allylic acetates (Z)‐18a and (Z)‐18b (Table 3). A similar loss of chemo selectivity as well as the loss of stereoselectivity in the coupling reactions of 19 with the bifunctional (E)‐olefins of type 18 was observed when the Li2CuCl4‐catalyst concentration was increased from 0.2 to 25 mol‐% or upon substitution of Li2CuCl4 by copper (I) chloride or iodide (Table 4).

Interference by phytol derivatives in the gas chromatographic analysis of fatty acids in the lipids of plant shoots

Interference by phytol derivatives in the gas chromatographic analysis of fatty acids in the lipids of plant shoots

The effect of copper deficiency on the photosynthetic apparatus of higher plants

Summary The effect of copper deficiency on the photochemical reactions, plastid pigments and lipoquinones of oat and spinach chloroplasts was investigated. The synthesis of all thylakoid prenyl lipids as well as of chlorophylls was lower during copper deficiency. The inhibition was observed to a different degree for the individual lipids. The formation of plastoquinones (C45-chain) was much more strongly inhibited than that of phytol derivatives and carotenoids. The rates of photosynthesis, expressed as O2 evolved per leaf area, were lower in the deficient than in the control plants. On the basis of chlorophyll, the O2-evolution was slightly higher in deficient plants. The Photosystem I activity of deficient chloroplasts measured in terms of O2-uptake and the photoreduction of NADP from water was much lower than that of the control ones. Cyclic photophosphorylation was inhibited to the same degree. Photosystem II activity was affected to a lesser extent. Plastocyanin and total copper content in deficient chloroplasts decreased over 50% in comparison with control chloroplasts. The effect of copper deficiency on electron transport was discussed with regard to the plastocyanin content of the chloroplasts.

The Occurrence of Phytylpyrophosphate and Acyl Esters of Phytol in Irradiated Dark‐Grown Barley Seedlings and Their Possible Role in Biosynthesis of Chlorophyll

AbstractDark‐grown barley seedlings which had been irradiated for 6 to 8 h have been shown to contain fatty acid esters of phytol. No such esters could be found in non‐irradiated seedlings. The fatty acids were saturated or had only one double bond. The most prominent acid was palmitic acid.Isolated etio‐chloroplasts from non‐irradiated and irradiated barley seedlings also contained phytylpyrophosphate. The ratio of free phytol to phytylpyrophosphate is only little changed when the seedlings are irradiated for 6 to 8 h. The chemical identifications of free phytol and the phytol derivatives are based upon combined gas chromatography/mass spectrometry.

Studies on the esterification of chlorophyllides

Methyl chlorophyllide a, but not chlorophyllide a, was esterified with phytol (or geranylgeraniol) in the presence of chlorophyllase from Chlorella protothecoides. No detectable esterifying activity was found when the pyrophosphate derivatives of phytol and geranylgeraniol were used.

Absorption and metabolism of uniformly 14C-labeled phytol and phytanic acid by the intestine of the rat studied with thoracic duct cannulation

1. 1. Tracer doses of uniformly 14C-labeled phytol were absorbed from the intestine of the rat to the extent of approx. 50% in 24 h. When the doses were increased to 300 mg, a smaller fraction was absorbed but the total quantity absorbed reached values as high as 65 mg. Over 70% of the absorbed phytol entered through the intestinal lymphatics. Phytol and cetyl alcohol were absorbed more slowly and less completely than were phytanic acid and palmitic acid, and less exclusively by way of the lymphatic route. 2. 2. Over half of the [ 14C] phytol radioactivity absorbed into the thoracic-duct lymph was still in phytol, some of which was free but a larger part of which was in the form of phytyl esters of fatty acids. The remainder of the label was in acidic derivatives of phytol, principally phytanic acid and phytenic acid (probably at least 3 isomers), which were present almost entirely in triglycerides and other complex lipids. The same derivatives were found in germ-free rats. No dihydrophytol was found in the lymph after phytol had been fed, and no phytenic acid was found after phytanic acid had been fed. Administered phytanic acid was absorbed into the lymph largely without change, except for its incorporation into triglycerides and other complex lipids. In contrast to the results with phytol, cetyl alcohol was largely converted to fatty acid during absorption. 3. 3. Significant quantities of radioactivity from [ 14C]phytol (administered to rats with intact thoracic ducts) were excreted in the bile, principally in the form of derivatives much more polar than phytanic acid.