"BIOMONITORED SYNTHESIS ROUTE FOR LARGE SCALE PREPARATION OFCARDOL(BILOBOL)AND11A-CARDOL". Phenolic compounds comprise a heterogeneous group of the secondary metabolism of the plants, though they can also be found in smaller amounts in animals and microorganisms. Phenolic lipids not originated from isoprenic units are relatively uncommon and can be considered as fatty acids which have the carboxyl group changed for the hydroxybenzene ring (Kozubek, 1999 and Alonso et al., 1997). Among those, the resorcinolic lipids, derived from mono and dihydroxyphenols have been subject to interdisciplinary studies for presenting a varied spectrum of biologic activities (Deszcz and Kosubek, 2000). Previous studies presented powerful bactericidal effect (Huang et al., 1980), moderated fungistatic properties (Adawadkar et a/., 1981), taking part in interactions among parasite plants and their hosts (Orabi et al., 1991), seed germination inhibitors (Matsumoto et al., 1990), among others. Among the biologic activities possibly related to the herbicidal effect of the resorcinolic lipids it can be mentioned: inhibition of DNA and RNA synthesis (Komolova et al., 1989); interaction with double stranded DNA molecules (Sing et al., 1995); interaction with photosystem proteins (Kieleczawa et al., 1987); key enzymes inhibition in the cellular metabolism such as trypsin (Kozubek, 1995), α-glucosidase, aldolase, sialidase (Aoyagi et al., 1.971 ), acid phosfatase (Kumagai et al., 1971 ), poligalacturonase (Kumagai et al., 1971), glucose-6- phosfate dehydrogenase (Irie et al., 1996), lactate dehydrogenase (Irie et al., 1996), among others; NAD-dependehts substrate oxidation inhibition with similar activity to rotenone (Rejman and Kozubek, 1997; Nenashevef a/., 1994); 3-phosphoglycerate dehydrogenase inhibition, a key enzyme acting on triacylglycerols synthesis (Irie et al., 1996); diminution in the phospholipids present in the double lipidic layer of the cellular membranes (Kozubek and Nienartowicz, 1995); fusiogenic activity (Kosubek and Skala, 1995); inhibition in the membrane enzymes activity such as phospholipase A2 and calcium dependent calmodulin-ATPase (Kosubek, 1992). ■Besides the antimicrobial and potentially herbicidal activity, the resorcinolic lipids also presented moluscide activity (Kubo and Komatsϋ, 1986), cytotoxic. (Arisawa et al., 1989), anthelmintic (Kubo and Komatsu, 1986), antitumoral (Ogiu et al., 1950; Kosubek, 1987; Tamai et al., 1990; Gasiorowski et al., 1996), antifeedant (Wierina, 1967; Sedlet et al., 1984) and antioxidant (Erin et al., 1987; Struski and Kozubek, 1992), In most cases, there were no direct correlation between the physiologic and biochemical roles of those compounds and their biological effects. Part of the effects can be explained by the amphyphilic nature of those biomolecules allowing for their interaction with the hydrophobic and hydrophilic domains of the cellular membrane proteins (Kosubeck, 1999). However such amphypatic properties are not enough to explain the spectrum of the biologic effects of the resorcinolic lipids. Moreover little is known about the biogenesis and the metabolism of those compounds in live organisms. There has been vast usage of resorcinolic lipids and it has been almost completely directed to the pharmaceutical market. There is a considerable number of patents related to the use of resorcinol as compounds in cosmetic formulation (Patent No. - JP04089419-A; JP2740043-B2), oral hygiene material (Patent No. - JP09241675), skin treatment material (Patent No. - JP03240718-A; JP2511163-B2), antineoplasic and anti-HIV drugs (Patent No. - JP06056657) among other applications. The resorcinol synthesis allows for obtaining substances of that class with better and high purity degree for testing biological and pharmaceutical activity. It also allows for the planning and obtaining of new biologically active substances with chemical structure analogous to the target product aiming potentializing its biologic activities. Due to the fact that resorcinolic compounds are produced in very low concentrations in the biologic systems it makes impossible the usage . of extraction processes from plants and microorganisms aiming to obtain products on a large scale and with a high degree of purity. The present invention aims to obtain the cardol and 11δ-cardol on a large scale by means of synthesis. It was developed an efficient and economically attractive synthesis route on all the aspects connected to production, which is object of protection of this patent. It is important to explain that this request has been reported exactly under the conditions in which the experiments were performed. Therefore in relation to the amount involved in the process and the quantity produced; we will be always relating in all parts of this report, to the same laboratorial scale by which this new route was developed once its production in industrial scale is nothing more than technical deduction with its technical adaptations. Furthermore in order to fulfill as close as possible the dispositions of AN 127 from May 15th, 1997, the routes development schemes related to the technical state will be treated as pictures as well as ours besides using the following numbering criteria for describing the items of the pictures: - (natural number and letter K), relating to the procedures and products of Kerrie et al., (1974). original route; - (natural number and letter T), relating to the procedures and products of Tyman et al., (1981 ); - Natural numbers only for the procedures and products generated in the route developed which is object of this patent. . Considering the facts exposed up to the present, three synthesis routes have been previously proposed by other authors as showed in pictures numbers 1 to 3 in this report. These pictures show us the following: Picture 1 - the route scheme developed by Kerrie A. Cirigottis et al., (1974); Picture 2 - route scheme later developed by Tyman et al., (1981); Picture 3 - synthesis sequence scheme recently proposed by Fϋrstner & Seidel (1997). They are all part of the technical state and they, all presented problems, which made it extremely difficult the medium and large scale production as presented below: The first one, shown in Picture 1 , was developed by Kerrie A. Cirigottis et al. (1974) for the synthesis of cardol. Besides being concluded in small scale it presented many problems on its conduction as shown below: 1- the acylation leading to the product (2K) worked only at low temperature (acetone - dry ice); 2- the diketone cleavage (2K) led to the production of a mixture of the desired product (3K) and 3,5-dimethoxy benzoic acid; 3- the efficient preparation of (3K) was satisfactorily performed only at -100C and for an extended period of 15 days; 4- the method for the reduction reaction of (3K) and the production of the product (4K) presented yield problems and the reduction using Wolff-Kishner procedure was followed by the demethylation and obtaining of the substance (5K); 6 - The (3K) hydrogenolysis in ethyl acetate and sulfuric acid produced a (4K) mixture and its ethyl ester, making necessary a methylation of the mixture with diazomethane, followed by its reduction with aluminum hydrate and lithium for obtaining alcohol (6K). 7 - In order to obtain the product (7K) it was used the Eisner Paul method, which uses a derivative of mercury and the product was not isolated in pure form; 8 - the demethylation of the product (K9) to end the synthesis of cardol was performed with methyl magnesium iodide in order to avoid the isomerization of the final product, which led to very low yield. Later on Tyman et al. (1981 ) developed a new route for the synthesis of cardol and 11δ-cardol shown in picture 2 in order to find a general solution for the preparation of saturated resorcinol. In the preparation of this route, that is Tyman et al., we present some problems, which are: 1- the synthesis presents yield problems (41 %) and generation of side products in the key intermediate preparation stage (13T); ' 2- usage of HMTP as co-solvent with high toxicity degree, besides being extremely pollutant; 3- the final stage of demethylation of methylic ether in the preparation of cardol as well as 11δ-cardol also presents yield problems and production of undesirable side-products. Another approach to resorcinolic derivatives synthesis, including the cardol, was performed by Fϋrstner & Seidel (1997). The synthesis sequence was planned aiming to reduce the number of steps and increase the yield of such preparations as shown in picture 3. This synthesis sequence proposed by Fϋrstner & Seidel is very efficient and presents high yield, however with the following problems: 1 - It requires the usage of very sophisticated and expensive reagents and catalizers, 2 - The route becomes non-attractive on a large scale perspective as the reaction conditions require expensive equipment and meticulous handling operations, and 3 - The final demethylation stage leading to cardol produces a mixture of substances, which must be later, separated by chromatography. This is an inconvenient fact from the point of view of global yield of the reaction, turning the production more expensive in purification processes. We have recently done exhaustive research on academic papers and on database in order to obtain the target, products prepared in this work. However we have not found specific studies referring to the object of this patent request apart from those previously related as shown below: Published articles: -"Long-chain phenols. Part. 23. Practical separations of the component phenols in technical cashew nut-shell liquid (Anacardium occidentale). Distillation procedures for obtaining cardanol". Journal of Chemical Technology and Biotechnology. 1982, 32(7), 681-90. Comment: the article is about separation aspect of the components of the Cashew-nut Liquid (LCC). -"5-Alkylresorcinols from Hakea trifurcata, that cleave DNA". Journal of the American Chemical Society. 1995, 11 (51 ), 12683-90. Comment: Phytochemical research about other kind of plant on which have been found members of the alkylresorcinolic similar to Cardol and 11δ-cardol. - "Isolation of δ-^Z-heptadecenyO-resorcinol from etiolated rice seedings as an antifungal agent." Phytochemistry, 1996, 41 (6), 1485- 9. Comment: Study about the isolation of resorcinol in rice seeds. - "Resorcinol-type resins from cashew nut-shell liquids". Anais da Associaςao Brasileira de Quimica. 1997, 46(3), 220-3., Comment: Article about general aspects of LCC components. - "Utilization of cashew nut-shell liquid from Anacardium occidentale as starting material for organic synthesis: a novel route to lasiodiplodin from cardols." Journal of the Brazilian Chemical Society. 1999, 10(1), 13-20. Comment: The study comprehends the utilization of LCC components as starting point material for the preparation of natural products. - "Zoosporicidal activities of Anacardic acids against Aphanomyces cochlioides." Zeitschrift fuer Naturforschung, C: Journal of Biosciences. 2002. 57(9/10), 874-82. Comment: The study is about the aspects of biologic evaluation of anacardic acids only. Deposited Patents: "Patent Abstracts of Japan. 2001. 2001-261693. Comment: Another Japanese patent now related to the preparation of glycosylated derivatives - "Method of inhibiting aldose reductase in diabetic hosts using phenol derivatives". 1993. US PATENT 5,202,355. Comment: Patent about antidiabetic activity of alkylated phenolic derivatives. -"Method for production of antioxidant of cashew nut. 1996. Russian Agency for Patents and Trademarks. 2069683 Cl Comment: Russian patent about anacardic acid isolation , extraction of cardol and cardanol and utilization of this rηaterial as antioxidant agents. , -"Separation and purification of alkenylresorcinol". 1998. Patent Abstracts of Japan, 10-259150. Comment: Japanese patent involving studies about alkylresorcinol separation not involving synthetic aspects. "Natural insecticide based on cashew-nut liquid (LCC) soluble in water". 2001. Brazilian Patent. Pl 9900889-0 A Comment: this patent was deposited and published by INPI and reports the formulation of natural insecticide with LCC. -" New O-glycoside type glycolipid and method for producing the same components of LCC. -"Coated granular substances". WO 03/048075 Al Comment: German patent describing the formulation of components of LCC for the usage as impermeabilizer. Therefore a low cost synthetic route for the preparation of cardol and 11δ-cardol based on Kerrie A Cirigottis et al. (1974) was elaborated. This' synthesis leads to the preparation of the same intermediates previously obtained in relation to the cardol synthesis, but their generation was optimized and/or modified in order to produce the target-substances on a large scale, according to the description below where the procedures performed in obtaining the same intermediates are compared and/or analogous procedures of the same kinds of reactions of these two routes. Therefore the main advantages obtained by the synthetic route subject of this patent over the route performed by Kerrie A Cirigottis et al., (1974) can be verified as follows: 1 ) Procedure: preparation of the intermediate (2), which is represented 'v by (2K) number on Kerrie route (1974), - On Kerrie's route (1974), acylation only at low temperature; - . On the object route of this patent, acylation at room temperature and with high yield after recycling the starting material; 2) Procedure: preparation of intermediate (3), which is represented by the number (3K) on Kerrie's route (1974), - On Kerrie's route (1974), production of a mixture containing the desired product (3K) besides the usage of low temperature (-1O0C) and long reaction time (15 days); - • On the object route of this patent, production of the desired product without the formation of side products and reaction to the room temperature and for a period of up to 15 hours; 3) Procedure: preparation of the intermediate (4), which is represented by the number (4K) on Kerrie's route (1974), - On Kerrie's route (1974) there were problems of yield and of obtaining the mixture of products, besides that, more than one ! reaction stage was used; - On the object route of this patent, high yield without the formation of products mixture and without the need of additional stage; 4) Procedure: preparation of the intermediate (8) which is represented by the number (7K) on Kerrie's route (1974), - On Kerrie's route (1974), employment of a method using mercury reagent and obtaining raw material; - On the object route of this patent, it was obtained pure material with no need of using mercury reagent; 5) Procedure: preparation of target product (10), which is represented by the number (10K) on Kerrie's route (1974), - On Kerrie's route (1974) the 9(K) demethylation was performed with low yield; - On the object route of this patent, it was obtained the target product (demethylated) with high yield; 6) Procedure: preparation of the intermediate (11 ), - Analogously this kind of reaction on Kerne's route (1974) is performed by using the co-solvent HMPT; - On the object route of this patent the coupling is performed on high yield without the HMPT co-solvent; 7) Procedure: preparation of the intermediate (12) Analogously, on Kerrie's route (1974), the halogenation is followed by the formation of side products; - On the object route of this patent, there is a high yield of the pure product; 8) Procedure: preparation of the intermediate (13), - Analogously, on Kerrie's route (1974) this kind of reaction is performed by using copper reagents; - On the object route of this patent, it is used organolithium reagent, on a mild condition, on the absence of HMPT co-solvent; 9) Procedure: preparation of the target product (15) , - The demethylation, on Kerrie's route (1974) was performed with low yield; - On the object route of this patent, the obtaining of the final product (demethylated) reached high yield; The route innovates with low room impact and each intermediate produced was evaluated in relation to its antifungal and herbicidal. .activity in order to monitor the synthesis relating chemical structure with biological activity. Pictures 4 and 5 in this report show respectively the schemes of the route developed in our study for the cardol and 11δ-cardol syntheses, for which we are applying for the patent. , . As it can be confirmed by pictures 4 and 5, the "BIOMONITORED SYNTHESIS ROUTE FOR LARGE SCALE PREPARATION OF CARDOL (B)LOBOL) AND 11A-CARDOL" object to this patent application is formed by 15 steps. The first 10 steps are concerned with the production of cardol starting from 3,5-dimethoxy benzoic acid in which we pass along the same intermediates of the original route of Kerrie et al. Which are 3,5- dimethoxybenzoyf chloride (1), 2-(3,5-Dimethoxy-benzoyl)-cyclohexanone (2), 7-(3,5- Dimethoxy-phenyl)-7-oxo-heptanoic acid (3), 7-(3,5-Dimethoxy- phenyl)-heptanoic acid (4), 7-(3,5-Dimethoxy-phenyl)-heptan-1-ol (6), 1,3- Dimethoxy-δ-pentadec-8-ynyl-benzene (8), 1,3-Dimethoxy-5-((Z)-pentadec- 8-enyl)-benzene (9), up to the target product ((Z)-5-Pentadec-8-enyl)- benzene-1,3-diol or Cardol (10), which had their obtaining processes substantially reformulated in order to improve the process. Two other phases were introduced among the 8 initial phases amounting to the 10 phases previously mentioned. Those two phases, exclusive to our route are placed between the steps (4) and (6), and (6) and (8), respectively, containing the new intermediates (5) 7-(3,5-Dimethoxy-phenyl)-heptanoic acid ethyl ester and (7) 1-(7-lodo-heptyl)-3,5-dimethhoxy-benzene, as well as their respective obtaining processes, also generated from the results optimization concept. In relation to the production of 11A-CARDOL, it starts from 1-(7-lodo- heptyl)-3,5-dimethhoxy-benzene (7); • being specifically introduced in this sequence the intermediates 10-(3,5-Dimethoxy-phenyl)-dec-2-yn-1-oI (11), 1- (10-lodo-dec-8-ynyl)-3,5-dimethoxy-benzene (12), 1,3-Dimethoxy-5- pentadeca-8,11-diynyl-benzene (13), 1,3-Dimethoxy-5-((8Z,11Z)-pentadeca- 8,11-dienyl)-benzene (14) and the target product ((8Z,11Z)-5-Pentadeca-8,11- dienyl)-benzene-1,3-diol (15) or δ-CARDOL, as well as the obtaining processes of these, all of them generated from the results optimization concept. Therefore, in relation to the new methods for obtaining the intermediates and their target product belonging to the routes for obtaining Cardol and 11δ- Cardol, object of this patent, we describe below the procedures involved in the preparation of each substance: 1) 3,5-dimethoxybenzoyl chloride (1), in a round bottom flask emerged in an ice bucket, equipped with drying tube, it is prepared a suspension of 3,5-dimethoxybenzoyl acid (25 g) in dichl.oromethane (250 mL) and dimethylformamide (20 mL) in which it is added thionyl chloride (20 mL). After the addition it is taken out of the bath and the agitation is kept for up to three hours at room temperature. The resulting solution is concentrated to be used in the following stage. 2) 2-(3,5-Dimethoxy-benzoyl)-cyclohexanone (2), in a round bottom flask supplied with reflux condenser and drying tube, it is prepared a solution of 4-cyclohex-1-enyl-morpholine (35 g) and dichloromethane (25 ml) and triethylamine (100 mL) to which it is added a solution of 3,5-dimethoxybenzoyl chloride (1 ) (27,5 g) and dichloromethane (75 mL) in agitation at room temperature. for 15 hours, adding afterwards a solution of concentrated acid (150 mL) at room temperature, performing the layers separation. The organic extract is concentrated until it is dry, and then it is dissolved in EtOAc. It is then washed in alkaline solution, water and saturated solution of NaCL After the organic extract is dry with Na2SO4 anhydrous, the solvent is evaporated and the residue is submitted to purification, obtaining the : product as a yellowish solid with 72% yield. 3) 7-(3,5- Dimethoxy-phenyl)-7-oxo-heptanoic acid (3), by adding product (2) (16,5 g) to a KOH (7,1 g) solution in ethanol (60 mL), stirring the mixture at room temperature from 10 to 15 hours, concentrating up to dryness, dissolving the content in distillated water (100 mL), acidifying and extracting with EtOAc, the organic extracts combined with water and saturated solution of NaCI are washed and dried with anhydrous Na2SO4 and, after the evaporation of the solvent, it is obtained a pure yellowish solid product with 95% yield. 4) 7-(3,5-Dimethoxy-phenyl)-heptanoic acid (4), by heating up a mixture of (3) (2,80 g), ethylene glycol (10 mL), hydrazine hydrate (5,0 mL) in alkaline pH, for up to a 2 hour period distilling the excess of hydrazine in a range of 195 to 2000C1 keeping it like that for more than 1 hour. After cooling, add water (50 mL), acidify the mixture and it is extracted with EtOAc. The organic extracts are washed and combined with water, NaCI saturated solution, the organic solvent is evaporated and the residue is submitted to purification, obtaining this product as yellowish oil with 90% yield. . 5) 7-(3,5-Dimethoxy-phenyl)-heptanoic acid ethyl ester (5), by heating a solution of (4) (1 ,54 g), hexane (20 mL), ethanol (30 mL) and p- toluenosulphonic acid (0,12) under reflux for up to 15 hours, concentrating the mixture, adding EtOAc, washing the organic layer with aqueous solution of NaHCO3, water, saturated solution of NaCI, drying with anhydrous Na2SO^ evaporating the solvent, submitting the residue to purification, obtaining this product as a slightly yellowish oil with 98% yield. 6) 7-(3,5-Dimethoxy-phenyl)-heptah-1-ol (6), by adding LiAIH4 (200 mg) in a solution of (5) (820 mg) in THF (20 mL), heating the mixture at reflux for 1 hour and, after cooling, add water slowly (12 mL), acidify the mixture, evaporate the excess of THF and extract the aqueous phase with EtOAc, washing the organic phase with diluted aqueous solution of NaHCO3, water and saturated solution of NaCI, drying with anhydrous Na2SO4, evaporating the solvent, submitting the residue to purification, obtaining this product as a slightly yellowish oil with 95% yield. 7) 1-(7-Iodo-heptyl)-3,5-dimethhoxy-benzene (7), by adding slowly to a solution of (6) (1 ,32 g) and triethylamine (2,0 mL) in acetone (15 mL), mesyl chloride (0,75 g), stirring the mixture at low temperature for 1 hour, evaporating the dichloromethane, adding water and EtOAc, separating the aqueous phase and washing the organic phase with diluted acid solution, NaHCO3, water, brine and drying with anhydrous Na2SO4, evaporating the solvent and dissolving the ; raw product in acetone, adding sodium iodide (2,50 g), heating the mixture at reflux for 1 hour, evaporating the acetone, adding water and EtOAc, separating the aqueous phase and washing the' organic phase with water and brine, drying with anhydrous Na2SO-J, evaporating the solvent and obtaining, under usual treatment, a clear oil, which then purified in the usual manner, gives 80% yield. 8) 1,3-Dimethoxy-5-pentadec-8-ynyl-benzene (8), by adding a solution cooled at 00C and in BuLi 2,5 M (2,2 mL) inert atmosphere, to a solution of 1-octyne (550 mg) in THF (4 mL) and after a period of 10 1 to 30 minutes it is added a solution of (7) (1 ,39 g) in THF (2mL), heating the mixture up to reflux for a period of 2 to 7 hours, and after cooling it is added a saturated solution of ammonium chloride, evaporating the THF and extracting the product with EtOAc, washing the organic phase with water, brine, drying with anhydrous Na2SO4, evaporating the solvent, submitting the residue to purification, ' obtaining this product with 75% yield. 9) 1,3-Dimethoxy-5-((Z)-pentadec-8-enyl)-benzene (9), preparing a suspension of 5% Pd-BaSO4 (50 mg) in ethanol (5,0 mL) by stirring at room temperature and hydrogen atmosphere from 15 to 40 minutes, and adding quinoline (two drops) and immediately after adding a solution of (8) (260 mg) in ethanol (15 mL) to the suspension and stirring the reagent mixture at room temperature under normal hydrogen atmosphere pressure, filtering the catalyzer over celite, concentrating the solution and purifying the residue, obtaining this product with 99% yield. 10) ((Z)-5-Pentadec-8-enyl)-benzene-1,3-diol or Cardol (10), adding '■' substance (9) (70 mg) and Na2CO3 (15 mg) to a solution of tiophenol 2M (1 ,0 ml_) in N-methyl-pyrrolidone, heating the mixture for 30 . minutes under inert atmosphere, adding, after cooling, glacial acetic acid, submitting the raw mixture to purification, obtaining this product with 85% yield. 11) 10-(3,5-Dimethoxy-phenyl)-dec-2-yn-1-ol (11), adding a cooled solution at 00C and at BuLi 2,5 M (5,50 ml_) inert atmosphere to a 3- (tetrahydropyranyloxy)-i-propyne (1,75 g) solution in THF (20 Ml) and after a 10 to 30 minute-period it is added a solution of (7) (3,62g) in THF (15 ml_) heating the mixture up to reflux for a 7-hour-period, after cooling it is added a saturated solution of ammonium chloride, evaporating the THF and extracting the product with EtOAc, washing the organic phase with water, NaCI saturated solution, drying with Na2SO4 anhydrous, evaporating the solvent, being the residue dissolved in ethanol (30 mL) and HCI 37% (5mL) and added to the mixture which was stirred at room temperature for one and a half hour and evaporating the solvent, it is added the, EtOAc, washing the organic phase with water, saturated solution of NaHCO3, saturated solution of NaCI, drying it with Na2SO4 anhydrous, evaporating the solvent, submitting the residue to purification, obtaining the product (11) with 90% yield. 12) 1-(10-lodo-dec-8-ynyl)-3,5-dimethoxy-benzene (12), by slowly adding to a solution of (11) (1 ,60 g) and triethylamine (600 mg) in dichloromethane (15mL), cooled in ice bath, a solution of mesyl chloride (800 mg) in dichloromethane (5 mL), stirring the mixture at room temperature for 2 hours, adding more dichloromethane and water, stirring the mixture, separating the aqueous phase and washing the organic phase with diluted acid solution, NaHCO3, water, brine, drying it with anhydrous Na2SO4, evaporating the solvent and dissolving the raw product in acetone (75 mL), adding the sodium iodide (3,3 g), heating the mixture at reflux for 1 hour, evaporating the acetone, adding water and EtOAc, separating the aqueous phase and washing the organic phase with water and brine, drying it with anhydrous Na2SO4, evaporating the solvent and obtaining, under usual treatment, a clear oil, which is purified, obtaining (12) with 76% yield. 13) 1,3-Dimethoxy-5-pentadeca-8,11-diynyl-benzene (13), by adding a BuLi 2,5 M (0,60 mL) solution to a 1-pentvne (120 mg) solution in ■■' THF (7,5 mL) cooled at 00C and at inert atmosphere. After a 20- minute-period it is added a solution of (12) (20 mg) in THF (5,0 mL), keeping the mixture in the ice bucket for a five-hour-period and then adding a saturated solution of ammonium chloride, evaporating the THF and extracting the product with EtOAc, washing the organic , phase with water and brine, drying it with Na2SO4 anhydrous, evaporating the solvent, submitting the residue to purification and obtaining this product with 80% yield. 14) 1,3-Dimethoxy-5-((8Z,11Z)-pentadeca-8511-dienyl)-benzene (14) preparing a suspension of 5% Pd-BaSO4 (20 mg) in ethanol (2,5 mL) in agitation at room temperature and under hydrogen atmosphere for a 30 min period, adding the quinoline (two drops) and immediately afterwards adding a solution of (13) (120 mg) in ethanol (7,5 mL) to the suspension and stirring the reagent mixture at room temperature under normal pressure of hydrogen atmosphere, filtrating the catalyzer over celite, concentrating the solution and purifying the residue, obtaining this product with 95% yield. 15) ((8Z,11Z)-5-Pentadeca-8>11-dienyl)-benzene-1,3-d«oI (15) or 11δ- CARDOL by adding the substance (14) (100 mg) and K2CO3 (50 mg) to a thiophenol 2M (2,0 mL) solution in N-methyl-pyrrolidone, heating the mixture for thirty minutes in inert atmosphere, adding, after cooling, glacial acetic acid and submitting the, raw mixture to purification, obtaining this product with 82% yield. All substances were isolated following usual procedures and characterized by conventional spectrometric methods.