PREPARATION METHOD OF ARENO[e]INDOLS

Abstract: The areno(e)indols have the formula (I). The methods comprises: (a) reacting (VI) with an aldehyde Ar''-CHO to obtain (VII); (b) oxidizing (VII) to yield the cetone (VIII); (c) reating (VIII) with a strong base and thereafter with an acyle chloride CICOR, to produce (IX); (d) subjecting to a photochemical cyclization (IX) to produce (I). In said formulas Ar is phenyl or substituted phenyl; Ar' is a radical (i) or )ii); R is an acyle group, Ar'' is a phenyl, pyrolyl, furanyl or thiophenyl group substituted up to three times by any of the radicals R, R¹, R², or R³. The compounds (I) are useful as intermediates in the synthesis of hexahydroareno(e)cyclopropa(c)indol-4-ones with antitumoral activity.

Description: TECHNICAL FIELD OF THE INVENTION The present invention is comprised in the technical field of the production of compounds with antitumoral activity. Specifically, the present invention refers to the obtainment of new areno indols, useful in the synthesis of hexahydroareno [e] cidopropa [c] indol-4-ones with antitumoral properties. PRIOR ART OF THE INVENTION Obtaining phenantrenes by oxidative photochemical cycling of stilbenes is a synthetic method largely used as can be seen in the review of F.B. Mallory and C.W. Mallory in Organic Reactions, Wiley: New York, 1984; Vol. 301 page 1. The analogous reaction of oxidative photocycling of 1-aryl-2-pyrrilethylenes (II) to produce areno [e] indols (III) is less described in the bibliography, in spite of its unquestionable potential. The reason is that this reaction tends to give very small yields and is highly dependent on the substrate. This small yield is often due to the oxidative decomposition in the reaction medium of the 1-aryl-2-pyrrolylethylenes (II) as starting products. A solution to this problem consists of the use of carefully studied reaction conditions to give the best yields in a given substrate. Hence, for example, M.P. Cava et al. in J. Org. Chem., 56, 2240 (1991) and cited references have carried out these oxidative cyclings on some 1-aryl-2-pyrrilethylenes (II), irradiating them with ultraviolet light in the presence of palladium on carbon, silica-gel, triethylamine and p-nitrobenzoic acid in acetonitrile to reflux and an inert atmosphere, with very good yields. These good yields are obtained however as a result of a laborious search for reaction conditions which end up being little versatile; furthermore, these conditions may end up to be technically complex to use. On the other hand, the areno [e] indols (III) are intermediates useful for preparing hexahydroareno [e] cyclopropa-[c] indol-4-ones (IV). These indolones have a great pharmaceutical interest as they contain the structural unity of cyclopropa [c] indol-4-one which, among others D.L. Boger et al. in J. Am. Chem. Soc., 113, 2779 (1991) have proven that it is responsible for the antitumoral activity of the CC-1065 agent (V) and synthesis analogues of the same. The object of the present invention is to solve the problem raised in the preparation of areno [e] indols (III) by photochemical irradiation in the presence of oxidants of 1-aryl-2-pyrrolylethylene (II). The problems associated with the photochemical cycling of 1-aryl-2-pyrrilethylenes (II) are solved in this invention by preparing compounds of general structure (IX) wherein the double central bond in the compounds of formula (II) is substituted by an arylsulfonyl group. This group acts by drawing out charge and therefore stabilizing the 1-aryl-2-pyrrolylethylene to which it is linked against undesired oxidations, which allows easy photocycling thereof leading to an areno [e] indol substituted with an arylsulfonyl group, that can be easily eliminated, if desired, by using a reducing agent capable of breaking the carbon sulfur bond. DETAILED DESCRIPTION OF THE INVENTION Just as is stated in the title hereof, the present invention refers to a method for preparing new areno [e] indols useful as intermediates in the synthesis of products with antitumoral activity. Said new areno [e] indols have the general formula (I): wherein -Ar represents phenyl or substituted phenyl, Ar' represents a condensed radical of formula: wherein R, R 1 , R 2 , R 3 may represent hydrogen, halogen, a linear or branched alkyl, alkenyl or alkynyl radical, a formyl, acyl, carboxy, akoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, hydroxy, alkoxy, amino, alkylamino, dialkylamino, acylamino or nitro radical and X represents oxygen, sulfur or a substituted or unsubstituted nitrogen and -R represents an acyl group with 2 to 5 linear or branched chain carbon atoms. The invention further refers to 1-aryl-2-pyrrolylethylene derivatives of general formula: wherein Ar, R have the meaning given above, and Ar'' has the meaning specified hereinbelow in respect of formula (VII). Said derivatives are useful in the preparation of the new areno [e] indols by photochemical cycling. In order to obtain the compounds of formula (I) one starts with a methyl 2-arylsulfinylmethyl-N-methoxymethyl-4-pyrrolecarboxylate of general formula (VI): wherein Ar has the meaning given above. These compounds of formula (VI) can be prepared, in turn, starting with methyl 2-formyl-pyrrolcarboxylate, a compound that is easily obtained by using the process described by H. J. Anderson, C.E. Loader and A. Foster in Cam. J. Chem., 58, 2527 (1980.) The treatment of methyl 2-formyl-4-pyrrolcarboxylated with chloromethyl ethyl ether in the presence of a base and an adequate organic solvent results in methyl 2-formyl-N-methoxymethyl-4-pyrrolcarboxylate. The base used is an alkoxide, a tertiary amine, an alkaline amide or an organolithic compound; the organic solvent is an aprotic dipolar solvent, an ether or a hydrocarboned solvent; the reaction time is between 1 and 40 hours and the temperature between -10 and 50º C. The reduction of methyl 2-formyl-N-methoxymethyl-4-pyrrolcarboxylate with a metal hydride in an organic solvent leads to the formation of methyl 2-hydroxymethyl-N-methoxymethyl-4-pyrrolcarboxylate. Normally, the preferred metal hydride is boron hydride and the organic solvent is an alcohol with a low molecular weight such as methanol or ethanol. The reaction temperature is generally between 0 and 40ºC and the time between 0.5 and 3 hours. The treatment of methyl 2-hydroxymethyl-N-methoxymethyl4-pyrrolcarboxylate with a substituted or unsubstituted benzenesulfinate in an acid medium gives rise to methyl 2-aryl-sulfinylmetho-N-methoxymethyl-4-pyrrolcarboxylate of general formula (VI) indicated above. In the same manner as the benzenesulfinate, 1-toluenesulfinate can be used, its counter-ion being a metallic cation, usually a sodium cation. The acid medium tends to be determined by an organic acid that is normally used as the solvent, for example, formic acid. The reaction temperature is normally between 0 and 50º C and the time between 0.5 and 3 days. The first step of the process of the invention includes reacting methyl 2-arylsulfinylmetyl-N-methoxymethyl-4-pyrrolcarboxylate (VI) with a strong base in an inert solvent and then with an aromatic aldehyde, obtaining as a product of the reaction the compounds methyl 2-(2-aryl-1-arylsulfonyl-2-hydroxyethyl)-N-methoxymethylpyrrol-4-carboxylate compounds of general formula: wherein Ar'' represents an aryl, phenyl, pyrrolyl, furyl or thiophenyl group substituted up to three times by any of the above mentioned radicals R, R 1 , R 2 , and R 3 and Ar has the meaning given above. The strong base used to obtain the compound of formula (VII) can be an alkaline amide, an alkyllithium or an aryllithium, preferably lithium diisopropylamide; the solvent has to be an inert solvent such as dialkyl ether, 1,4-dioxane or tetrahydrofuran, preferably tetrahydrofuran, and the aldehyde an aromatic aldehyde, such as methyl 2-formyl-N-methoxymethylpyrrole4-carboxylate, 4-methoxybenzaldehyde or 3,4,5-trimethoxybenzaldehyde. The compounds of formula (VII) obtained are oxidized in an inert solvent to give the corresponding ketone of general formula: wherein -Ar and -Ar'' have the above cited meaning. The oxidant used is 2,3-dicyano-5,6-dichloro-p-benzoquinone and the inert solvent benzene, toluene, xylene, 1,4-dioxane or chlorobenzene. The ketone of general formula (VIII) is subjected to acylation by treating it with a suitable base in an inert solvent and then with an acyl chloride as an acylating agent, obtaining the acylated derivate of general formula: wherein Ar, Ar'' and R have the meaning given above. The base used can be an amine, an alkaline amide, an alkyllithium or an aryllithium, preferably triethylamine; the inert solvent may be chloroform, dichloromethane or 1,2-dichloroethane and the acylating agent a chloride of an acid having 2 to 5 linear or branched chain carbon atoms, preferably acetyl chloride. To obtain a compound of general formula (I), the compound of formula (IX) is subjected to a photochemical cycling process in an organic solvent, preferably an alcohol with a low molecular weight such as methanol or ethanol, in the presence of an oxidant, such as oxygen associated catalytic iodine, and under ultraviolet irradiation. The compound obtained by this photochemical cycling process from the acylated derivative of formula (IX) is a compound of general formula (I), an intermediary product in the synthesis of compounds with antitumoral activity. In a first embodiment, the compounds of general formula (I) they have the following structural formula: wherein R represents an acyl group of 2 to 5 linear or branched chain carbon atoms and Ar represents phenyl or substituted phenyl. In a second embodiment, the compound of general formula (I) have the following structural formula: wherein R represents an acyl group of 2 to 5 linear or branched chain carbon atoms and Ar represents phenyl or substituted phenyl. In a third embodiment, the compound of general formula (I) have the following structural formula: wherein R represents an acyl group of 2 to 5 linear or branched chain carbon atoms and Ar represents phenyl or substituted phenyl. EMBODIMENTS OF THE INVENTION The present invention is illustrated with the following example, that are not intended to limit at all the scope of the applicability thereof. In order to describe the physical data of the synthesized compounds the following abbreviations are used: m.p.: melting point IR: infrared UV: ultraviolet 1 H-NMR: nuclear magnetic resonance S: singlet d: doblet t: triplet m: multiplet J: coupling constant MS: mass spectrum ei: electronic impact FAB: fast atom bombardment M + : molecular ion ⊘: diameter TS: tosyl=p-toluenesulfonyl EXAMPLE OF PREPARATION Preparation of methyl N-methoxymethyl-2-tosylmethyl-4-pyrrolcarboxylate Step 1 : Preparation of methyl 2-formyl-N-methoxymethyl-4-pyrrolcarboxylate A solution of 5.995 g of methyl 2-formyl-4-pyrrolecarboxylate is prepared in 60 mL of dry N,N-dimethylformamide, in a flask provided with a calcium chloride tube. To this solution, magnetically stirred and cooled in an ice/water bath, 7.323 g. of potassium tert-butoxide were added. When the addition was ended, the reaction is left to room temperature and the stirring is maintained for 1.75 hours, after which the reaction is cooled again in an ice/water bath and 6 mL of chloromethyl ethyl ther are added slowly. After the addition is finished the reaction is left to room temperature and the stirring is maintained for 18 hours. Thereafter, by thin layer chromatography analysis the existence of the starting product is tested, so that, by repeating the same process used above, 1.864 g. of potassium tert-butoxide and 1.5 mL of chloromethyl methyl ether were added, leaving the stirring at room temperature for 16 more hours. The preparation is carried out by adding water and extraction with ethyl acetate, followed by drying the organic phase with sodium sulfate and elimination of the solvent in a rotatory evaporator, resulting in an oil that is purified by silica gel column chromatography (25x3 cm ⊘), by elution with dichloromethanol/ethyl acetate (20:1.) 6.817 g. of protected pyrrole are obtained. Yield: 88% m.p.: 65-66º C (petroleum ether:diethyl ether) IR(KBr, maximum ν): 1670, 1705, 2950, 3115 cm -1 UV (ethanol, maximum λ): 220, 278 nm. 1 H-NMR (CDCl 3 ): 3.34 (s, 3H, ArCH 2 OCH 3 ), 3.85 (s, 3H, ArCO 2 CH 3 ), 5.67 (s, 2H, ArCH 2 OCH 3 ), 7.39 (d. 1H, J=1.6Hz, ArH), 7.69 (s wide, 1H, ArH), 9.62 (d, 1H, J= 0.8Hz, ArCHO) ppm. MS (e.i., m/e, %): 197 (M + , 29) 182 (M +. -CH 3 , 100), 166 (M +. -OCH 3 , 28), 154 (M +. -CH 3 CO, 23.) Step 2 : Preparation of methyl 2-hydroxymethyl-N-methoxymethyl-4-pyrrolecarboxylate 165 mg. NaBH 4 are added to a magnetically stirred solution cooled in an ice/water bath of 515 mg. of methyl 2-formyl-N-methoxymethyl-4-pyrrolecarboxylate in 8 mL of dry methanol, in a flask provided with a calcium chloride tube. After the addition has been ended, stirring is maintained for 1.5 hours. Addition of water to the reaction mixture followed by elimination of the methanol in the rotatory evaporator, extraction with ethyl acetate, drying the organic phase with sodium sulfate and elimination of the solvent in the rotatory evaporator, gives rise to an oil, which is purified by silica gel column chromatography (15x2 cm ⊘), by elution with dichloromethane / ethyl acetate (5:1), whereby 507 mg of the desired alcohol are obtained. Yield: 98% m.p.: 56-57º C (ethyl acetate:hexane) IR (KRr, maximum ν ): 1710, 2950, 3120, 3400 wide cm -1 UV ethanol, maximum λ): 208, 225, 260 shoulder nm 1 H-NMR (CDCl 3 ): 3.29 (s, 3H, ArCH 2 OCH 3 ), 3.80 (s, 3H, ArCO 2 CH 3 ), 4.61 (s, 2H, ArCH 2 OH). 5.28 (s, 2H, ArCH 2 OCH 3 ), 6.60 (d, 1H, J= 1.6Hz, ArH), 7.40 (d, 1H, J= 1.7Hz, ArH) ppm MS (e.i., m/s, %): 199 (M +. , 182 (M +. -OH,3), 168 (M +. -OCH 3 , 13) 45 (CH 3 OCH 2 +, 100). Step 3 : Preparation of methyl N-methoxymethyl-2-tosylmethyl-4-pyrrolecarboxylate A solution of 438 mg. methyl 2-hydroxymethyl-N-methoxymethyl-4-pyrrolecarboxylate and 1.881 g. of sodium p-toluenesulfinate in 5 mL of aqueous 85 % formic acid is stirred at room temperature for 23 hours. Addition of water to the reaction mixture, followed by extraction with dichloromethane, drying of the organic phase with sodium sulfate and elimination of the solvent in the rotatory evaporator, leads to a solid that is purified by means of a silica gel column (15x1.5 cm, ⊘), with elution with dichloromethane:ethyl acetate (20:1), whereby 702 mg. of sulfone are obtained. Yield: 95% m.p.: 104-105º C (ethyl acetate: petroleum ether) IR (KBR, maximum ν ): 1705. 2940, 3120 cm -1 IV ethanol, maximum λ): 202, 208, 226 nm 1 H-NMR (CDCl 3 ): 2.44 (s, 3H, ArCH 3 ), 3.17 (s, 3H, ArCH 2 OCH 3 ), 3.77 (s. 3H, ArCO 2 CH 3 ), 4.42 (s, 2H, ArCH 2 Ts), 5.27 (s, 2H, ArCH 2 OCH 3 ). 6.30 (d, 1H, J= 1.3 Hz, ArH),7.30 (d, 2H, J= 8.2Hz, ArH), 7.38 (d, 1H, J= 1.7 Hz, ArH), 7.57 (d, 2H, J= 8.2Hz, ArH) ppm. MS (e.i., m/s, %), 337 (M +. , 0.3), 306 (M +. -OCH 3 ,3), 1.82 (M +. - SO 2 (C 6 H 4 )CH 3 , 100). EXAMPLE 1 1) Methyl 2-[2-hydroxy-2-(4-methoxycarbonyl-N-methoxymethyl-2-pyrrolyl)-1-tosylethyl]-N-methoxymethyl-4-pyrrolecarboxylate A solution of lithium diisoproplyamide is prepared by adding 0.8 mL of a 2.7M solution of n-butyl-lithium in hexane on a solution of 0.31 mL of diisopropylamine in 20 mL of tetrahydrofuran. 600 mg. of methyl N-methoxymethyl2-tosylmethyl-4-pyrrolecarboxylate are added to the solution of lithium diisopropylamide stirred magnetically and cooled to -75º C. The temperature of the resulting suspension is left to rise to -40º C for 1.25 hours and on the generated red solution 351 mg. of methyl 2-formyl-N-methoxymethyl-4-pyrrolecarboxylate are added. The temperature of the reaction mixture is left to rise to -15º C for 2 hours and 5 mL of hydrochloric acid (10 %) are added. Addtion of 20 mL of brine, followed by extraction with diethyl ether, drying of the organic phase with sodium sulfate and elimination of the solvent in a rotatory evaporator, leads to a solid residue that is purified on silica gel column chromatography (18x2 cm ⊘), using an elution gradient of dichloromethane/ethyl acetate increasing the proportion of ethyl acetate from 15 to 25 %. 921 mg. of the condensation product is obtained as a sole diastereoisomer. Yield: 97% m.p.: 180-181º C (ethyl acetate) IR (KBr, maximum ν): 1688, 1715, 2950, 3120, 3460 cm -1 UV (ethanol, maximum ): 205, 225 shoulder , 255 shoulder nm 1 H-NMR (CDCl 3 ): 2.40 (S, 3H, ArCH 3 ), 3.08 (s, 3H, ArCH 2 OCH 3 ) 3.17 (s, 3H, ArCH 2 OCH 3 ), 3.67 (s, 3H, ArCO 2 CH 3 ) 3.71 (s, 3H, ArCO 2 CH 3 ), 4.06 (d, 1H, J=3.7 Hz, ArCH(R)OH) 4.70 (d, 1H, J= 11.4 Hz, ArCH 2 OCH 3 ), 5.09 (m, 2H, ArCH 2 OCH 3 and ArCH(Ts)R), 5.36 (d, 1H, J = 11.5 Hz, ArCH 2 OCH 3 ), 5.37 (d, 1H, J = 10.7 Hz, ArCH 2 OCH 3 ), 5.54 (dd, 1H, J = 2.6 and 10.4 Hz, ArCH(OH)R), 6.42 (d, 1H, J = 1.3 Hz, ArH), 6.49 (d, 1H, J = 1.5 Hz, ArH), 7.18 (m, 2H, ArH), 7.25 (d, 2H, J = 7.9 Hz, ArH) 7.57 (d, 2H, J = 8.3 Hz, ArH) ppm. MS (FAB, m/s, %): 535 (M+1H 2 O, 29), 503 (M+1-CH 3 OH, 28), 489 (M+1-CH 3 OCH 3 ,6), 379 (M+1-CH 3 (C 6 H 4 )SO 2 H, 4), 362 M+1+H 2 O-CH 3 (C 6 H 4 )SO 2 ,100), 348 (M+1-CH 3 (C 6 H 4 )SO 2 H-OCH 3 , 21), 333 (M+1-CH 3 (C 6 H 4 )SO 2 H-CH 3 OCH 3 , 9) 315 (M+1-CH 3 (C 6 H 4 )S0 2 H-CH 3 OCH 3 -H 2 0, 61) 182 (ArCH 2 A, 83). 2) Methyl 2-[2-hydroxy-2-(4-methoxyphenyl)-1-tosylethyl]-N-methoxymethyl-4-pyrrolecarboxylate A solution of lithium diisopropylamide is prepared by adding 4.21 mL of a 2.4M solution of -n-butyl-lithium in hexanes on a 1.5 mL solution of diisopropylaminde in 100 mL of tetrahydrofuran. 2.9 g. of methyl N-methoxy-2-tosylmethyl-4-pyrrolecarboxylate are added to a solution of lithium diisopropylamide stirred magnetically and cooled to -50º C. 2 hours later 1.06 mL of methoxybenzaldehyde are added on the generated red solution. 1 hour later HCl 10 % is added. Addition of brine, followed by extraction with diethyl ether, drying the organic phase with sodium sulfate and elimination of the solvent in a rotatory evaporator, leads to a dry residue that is purified by silica gel column chromatography (27x3.5 cm ⊘), by elution with dichloromethane/ethyl acetate (3:1.) 3.58 g. of the condensation product are obtained as two diasteroeoisomers in the ratio of 3:1. Yield: 88 % IR (film, maximum ν ): 1560, 1610, 1710, 2960, 3480 cm -1 UV (ethanol, maximum λ): 204, 328 nm 1 H-NMR (CDCl 3 ): 2.37 (s, ArCH 3 , minority), 2.40 (s, CH 2 OCH 3 , minority), 2.42 (s, ArCH 3 , majority), 2.50 (s, CH 2 OCH 3 , majority), 3.70 (s, CO 2 CH 3 , majority + minority), 3.79 (s, ArOCH 3 , majority + minority), 4.05 (d, J = 11.3 Hz, NCH 2 OCH 3 , minority), 4.39 (d, J = 11.13 Hz, NCH 2 OCH 3 , minority). 4.39 (d, J = 11.3 Hz, NCH 2 OCH 3 majority), 4.48 (d, J = 11.3 Hz, NCH 2 OCH 3 , minority) 4.56 (d, J = 1.9 Hz, HCOH, minority), 4.75 (d, J = 9.8 Hz, HCOH, majority), 4.78 (d, J = 11.3 Hz, NCH 2 OCH 3 , majority), 5.33 (d, J = 9.8 Hz, CHTs, majority), 5.80 (d, J = 1.9 Hz, CHTs, minority), 6.61 (d, J = 1.4 Hz, ArH, majority), 6.68 (d, J = 8.7 Hz, ArH, majority), 6.71 (d, J = 8.6 Hz, ArH, minority), 7.00 (d, J = 1.4 Hz, ArH, majority + minority), 7.02 (d, J = 8.6 Hz, ArH, minority), 7.14 (d, J = 8.7 Hz, ArH. majority), 7.27 (d, J = 8.3 Hz, ArH, majority), 7.37 (d, J = 1.4 Hz, ArH, minority), 7.57 (d, J = 8.3 Hz, ArH, majority + minority), 7.64 (d, J = 8.3 Hz, ArH, minority) MS (FAB, m/s, %): 474 (M+1.7), 476 (M+1-H 2 O, 63) 442 (M+1-HOCH 3 , 3) 318 (M+1-TsH,24), 301 (M+1-H 2 O-TsH, 70), 286 (M+1-HOCH 3 -TsH, 67) 258 (M+1-HOCH 3 -TsH-CO, 23.) 3) Methyl 2- [2-hydroxy-2-(3,4,5-trimethoxyphenyl)-1-tosylethyl]-N-methoxymethyl-4-pyrrolecarboxylate A solution of lithium diisoproplylamide is prepared by adding 4.8 mL of a solution of 2.44M n-butyl-lithium in hexanes on a solution of 1.9 Ml of diisopropylamine in 70 mL of tetrahydrofuran. 3.0 g. of methyl N-methoxymethyl-2-tosylmethyl-4-pyrrolecarboxylate are added to the solution of lithium diisopropylamide stirred magnetically and cooled to -80º C. The resulting suspension is left stirring at -50º C for 2.3 hours and 1.75 g. of 3,4,5-trimethoxybenzaldehyde are added to the generated red solution. After 1.5 hours of stirring at -50º C the reaction is cooled to -70º C and 100 ml. of hydrochloric acid (10%) are added. Extraction with diethyl ether, followed by drying of the organic phase with sodium sulfate and elimination of the solvent in the rotatory evaporator, leads to a solid residue that is purified by recrystallization of dichloromethanecyclohexane, giving a first fraction that is mixed with a second fraction of product, result of concentrating the mother liquors, dissolving the residue in methanol, adding cyclohexane and filtering the resulting precipitate. 3,15 g. of the condensation product are obtained as two two diasteroisomers in the ratio of 3:1. Yield: 66 % m.p. 80-90º C IR (film, maximum ν): 1590, 1710, 2950, 3000. 3470 cm -1 UV (ethanol, maximum λ): 282 nm 1 H-NMR (CDCl 3 ): 2.34 (d, J = 1.3Hz, ArCH 3 minority), 2.40 (t, J = 1.5 Hz, ArCH 3 majority), 3.85-3.65 (m, ArOCH 3 + CO 2 CH 3 + CH 2 OCH 3 , majority + minority), 3.98 (d, J = 1.7 Hz, NCH 2 OCH 3 minoirty). 4.43 (d, J = 10.8 Hz, NCH 2 OCH 3 majority), 4.45 (d, J = 1.7 Hz, NCH 2 OCH 3 minority), 4.76-4.62 (m, HCOH + HCTs, majority + minority), 5.32 (d, J = 9.5 Hz, NCH 2 OCH 3 majority), 5.85 (s, OH) 633 (d, J = 1.1 Hz, ArH minority), 6.44 (d, J = 1.3 Hz, ArH majority), 6.73 (s, ArH majority), 6.98 (t, J = 1.6 Hz, ArH majority), 7.08 (t, J = 1.6 Hz, ArH minority), 7.24 (d, ArH minoirty), 7.25 (dd, ArH majority), 7.34 (s, ArH minority), 7.57 (dd, J = 1.5 and 8.4 Hz, ArH majority), 7.61 (d, J = 6.9 Hz, ArH minority) ppm. EXAMPLE 2 1) Methyl 2- [2-(4-methoxycarbonyl-N-methoxymethyl-2-pyrrolyl)-2-oxo-1-tosylethyl]-N-,ethoxymethyl-4-pyrrolecarboxylate A mixture of 2.35 g. of methyl 2-[2-hydroxy-2-(4-methoxycarbonyl-N-methoxymethyl-2-pyrrolyl)-1-tosylethyl]-N-methoxymethyl-pyrrolecarboxylate and 2.51 g. of 2,3-dicyano-5,6-dichloro-p-benzoquinone in 25 mL of dry benzene is heated to reflux under argon for 24 hours. Addition of 100 mL of a saturated solution of Na 2 S 2 O 5 , followed by extraction with dichloromethane, washing the organic solution with a saturated Na 2 S 2 O 5 solution, drying with sodium sulfate and concentration of the same, gives rise to an oil that is purified by silica gel column chromatography (20x2 cm ⊘), by elution with ethyl acetate/hexane (1:1) to give rise to 2.20 g. of the desired ketone. Yield: 92 % m.p.: 58-60º C (ethyl acetate-hexane) IR (KBr, maximum ν): 1670, 1718, 2950, 3120 cm -1 UV (ethanol, maximum λ): 208, 222 shoulder , 293 nm 1 H-NMR (CDCl 3 ): 2.39 (s, 3H, ArCH 3 ); 3.27 (s, 6H, ArCH 2 OCH 3 ), 3.71 (s, 3H, ArCO 2 CH 3 ), 3.79 (s, 3H, ArCO 2 CH 3 ), 4.92 (d, 1H, J = 11.1 Hz, ArCH 2 OCH 3 ), 5.58 (d, 1H, J = 10.2 Hz, ArCH 2 OCH 3 ), 5.61 (d, 1H, J = 10.2 Hz, ArCH 2 OCH 3 ), 6.04 (d, 1H, J = 11.1 Hz, ArCH 2 OCH 3 ), 6.27 (s, 1H, ArCH (Ts)R), 6.47 (d, 1H, J = 1.7 Hz, ArH), 7.22 (d, 2H, J = 8.2 Hz, ArH), 7.42 (d, 1H, J = 1.8 Hz, ArH), 7.50 (d, 2H, J = 8.3 Hz, ArH), 7.59 (d, 1H, J = 1.7 Hz, ArH), 7.64 (d, 1H, J = 1ï7 Hz, ArH) ppm. MS (e.i., m/s %): 532 (M +. , 1), 501 (M +. -CH30.8), 377 (M +. -CH 3 (C 6 H 4 )SO 2 , 94), 395 (M +. -CH 3 O-CH 3 (C 6 H 4 )SO 2 H. 99) 317 (M +. -CH 3 O-CH 3 (C 6 H 4 )SO 2 H-CO, 100), 196 (ArCO + , 44), 182 (ArCH 2 +, 22), 139 (CH 3 (C 6 H 4 )SO +. , 11) 91 (CH 3 (C 6 H 4 ) + , 16). 2) Methyl 2-[2-(4-methoxyphenl)-2-oxo-tosylethyl] -N-methoxymethyl-4-pyrrolecarboxylate A mixture of 1.42 g. of methyl 2-[2-hydroxy-2-(4-methoxyphenyl)-1-tosylethyl] -N-methoxymethyl-4-pyrrolecarboxylate and 1.7 g. of 2,3-dicyano-5,6-dichloro-p-benzoquinone in 70 mL of dry toluene is heated to reflux under argon for 12 hours. Addition of a saturated solution of Na 2 S 2 O 5 , followed by extraction dichloromethane, washing the organic solution with a saturated solution of Na 2 S 2 O 5 , drying with sodium sulfate and concentrating the same, gives rise to an oil that can be purified by silica gel column chromatography (35x3 cm ⊘), by elution with ethyl acetate/hexane (1:1) to give rise to 1,27 g. of the desired ketone. Yield: 90 % m.p.: 108-109º C IR (film, maximum ν): 1570, 1600, 1680. 1715 cm -1 UV (ethanol, maximum λ): 294, 222 nm) 1 H-NMR (CDCl 3 ): 2.44 (s, 3H, ArCH 3 ), 3.26 (s, 3H, NCH 2 OCH 3 ), 3.73 (s, 3H, CO 2 CH 3 ), 3.85 (s, 3H, ArOCH 3 ), 4.97 (d, 1H, J = 11.1 Hz, NCH 2 OCH 3 ), 6.24 (d, 1H, J = 11.1 Hz, NCH 2 OCH 3 ), 6.39 (d, 1H, J = 1.8 Hz, ArH), 6.54 (s, 1H, HCTs), 6.89 (d, 2H, J = 9.0 Hz, ArH), 7.26 (d, 2H, J = 8.3 Hz, ArH) 7.46 (d, 1 H, J = 1.8 Hz, ArH), 7.52 (d, 2H, J = 8.3 Hz, ArH), 7.96 (d, 2H, J = 9.0 Hz, ArH) ppm. MS (e.i., m/s, %) 471 (M +. , 3), 316 (M +. -TsH, 100), 135 (CH 3 O(C 6 H 4 )CO + , 49), 91 (CH 3 C 6 H 4 +, 19). 3) Methyl 2-[2-(3,4,5-trimethoxyphenyl)-2-oxo-1-tosylethyl]-N-methoxymethyl-4-pyrrolecarboxylate A mixture of 2.65 g. of methyl 2-[2-hydroxy-2-(3,4,5-trimethoxyphenyl)-1-tosylethyl]-N-methoxymethyl-4-pyrrolecarboxylate and 3.95 g. of 2.3-dicyano-5,6-dichloro-p-benzoquinone in 90 mL of dry toluene is dried to reflux under argon for 9 hours. The elimination of toluene gives rise to a dark residue that is dissolved in dichloromethane. The resulting solution is filtered, washed with an aqueous saturated Na 2 SO 3 solution and concentrated, yielding a residue that is purified by silica gel column chromatography, by elution with dichloromethane-ethyl acetate (9:1), giving rise to 1.63 g. of the desired ketone. Yield: 62 % 1 H-NMR (CDCl 3 ): 2.46 (s, 3H, ArCH 3 ), 3.27 (s, 3H, NCH 2 OCH 3 ), 3.75 (s, 3H, CO 2 CH 3 ), 3.84 (s, 6H, ArOCH 3 ), 3.94 (2, 3H, ArOCH 3 ), 5.00 (d, 1H, J = 11 Hz, NCH 2 OCH 3 ), 6.26 (d, 1H, J = 11 Hz, NCH 2 OCH 3 ), 6.36 (d, 1H, J = 1.7 Hz, ArH), 6.54 (s, 1H, HCTs), 7.27 (s, 2H, ArH), 7.28 (d, 2H, J = 8.4 Hz, ArH), 7.48 (d, 1H, J = 1 Hz, ArH), 7.5 (d, 2H, J = 8.4 Hz, ArH) ppm. EXAMPLE 3 1) Methyl 2-[2-acetoxy-2-(4-methoxycarbonyl-N-methoxymethyl-2-pyrrolyl)-1-tosylethenyl]-N-methoxymethyl-4-pyrrolecarboxylate 4.4 mL of acetyl chloride are slowly added to a solution, magnetically stirred and kept at -40º C under argon, of 4.67 g. of methyl 2-[2-(4-methoxycarbonyl-N-methoxymethyl-2-pyrrolyl)-2-oxo-1-tosylethyl]-N-methoxy methyl-4-pyrrolecarboxylate and 12.1 mL of triethylamine in 60 mL of dry dichloromethane. After 2.25 hours, 100 mL of hydrochloric acid 10 % are added and extracted with dichloromethane. Drying with sodium sulfate and concentrating the organic phase yields an oil that is purified by silica gel column chromatography (18x3 cm ⊘), by elution with a hexaneethyl acetate gradient of 40 to 60 % in ethyl acetate. 4.96 g. of enol acetate. Yield: 98 % m.p. 59-61º C (Dichloromethane-ethyl acetate) IR (film, maximum ν ): 1720, 1785, 2880, 2960 cm -1 UV (ethanol, maximum λ): 205, 302, 315 shoulder nm 1 H-MNR (CDCl 3 ): 2.32 (s, 3H, ArOCOCH 3 ), 2.42 (s, 3H, ArCH 3 ), 2.99 (s, 3H, NCH 2 OCH 3 ), 3.20 (s, 3H, NCH 2 OCH 3 ) 3.69 is, 3H, ArCO 2 CH 3 ), 3.76 (s, 3H, ArCO 2 CH 3 ), 4.82 (d, 1H, J = 10.6 Hz, ArCH 2 OCH 3 ), 4.99 (d, 1H, J = 10.6 Hz, ArCH 2 OCH 3 ), 5.13 (d, 1H, J = 10.6 Hz, ArCH 2 OCH 3 ), 5.23 (d, 1H, J = 10.6, ArCH 2 OCH 3 ), 6.26 (d, 1H, J = 1.8 Hz, ArH), 6.47 (d, 1H, J = 1.8 Hz, ArH), 7.27 (d, 2H, J = 8.1 Hz, ArH), 7.31 (d, 1H, J = 1.7 Hz, ArH), 7.40 (d, 1H, J = 1.8 Hz, ArH), 7.62 (d, 2H, J = 8.3 Hz, ArH) ppm. MS (e.i., m/s, %): 574 (M +. , 4), 543 (M +. -CH 3 O, 7) 532 (M +. -CH 2 CO, 75), 500 (M +. -CH 3 OH-CH 2 CO, 20), 377 (M +. -CH 2 CO-CH 3 (C 6 H 4 )SO 2, 32), 345 (M +. -CH 3 OH-CH 2 CO-CH 3 (C 6 H 4 ) SO 2 , 90), 317 (M +. -CH 3 OH-CH 2 CO-CH 3 (C 6 H 4 )SO 2 -CO, 54), 196 100), 139 (ArCO + , 41), 182 (ArCH 2 +, 100), 139 (CH 3 (C 6 H 4 )SO +. , 24), 91 (CH 3 (C 6 H 4 )+, 18.) 2) Methyl 2-[2-acetoxy-2-(4-methoxyphenyl)-1-tosylethenyl]-N-methoxymethyl-4-pyrrolecarboxylate 1.34 mL of acetyl chloride are slowly added on a solution, magnetically stirred and kept at -40º C under argon, of 1.27 g. of methyl 2-[2-(4-methoxyphenyl)-2-oxo-1-tosylethyl]-N-methoxymethyl-4-pyrrolecarboxylate and 3.76 mL of triethylamine in 60 mL of dry dichloromethane. After 2 hours 20 mL of hydrochloric acid 10 % are added and extracted with dichloromethane. Drying with sodium sulfate and concentration of the organic phase gives an oil that is purified by silica gel column chromatography (30x3 cm ⊘), by elution with hexane-ethyl acetate (1:1). 1.34 g. of enol acetate are obtained as the sole isomer. Yield: 97 % m.p. 152.5-153.5º C IR (film, maximum ν): 1510, 1550, 1595, 1780, 2955 cm -1 UV (ethanol, maximum λ : 298, 212 nm 1 H-NMR (CDCl 3 ): 2.42 abd 2,43 (s, 3H, ArCH 3 and ArOCOCH 3 ), 3.00 (s, 3H, NCH 2 OCH 3 ), 3.74 (s, 3H, ArCO 2 CH 3 ), 3.79 (s, 3H, ArOCH 3 ), 4.64 (d, 1H, J = 10.3 Hz, NCH 2 OCH 3 ), 5.00 (d, 1H, J = 10.3 Hz, NCH 2 OCH 3 ), 6.44 (d, 1H, J = 1.7 Hz, ArH), 6.69 (d, 2H, J = 9.0 Hz, ArH), 7.12 (d, 2H, J = 9.0 Hz, ArH), 7.28 (d, 2H, J = 8.3 Hz, ArH), 7.54 (d, 1H, J = 1.7 Hz, ArH), 7.68 (d, 1H, J = 8.3 Hz, ArH) MS (FAB, m/s, %): 514 (M+, 9), 471 (M+1-CH 2 CO, 37) 440 (M+1-CH 2 CO-CH 2 OCH 3 , 30) 135 (CH 3 O(C 6 H 4 ) + , 100), 284 (M+1-CH 2 CO-CH 2 OCH 3 -TsH, 33). 3) Methyl 2-[2-acetoxy-2-(3,4,5-trimethoxyphenyl)-1-tosylethenyl]-N-methoxymethyl-4-pyrrolecarboxilate 0.24 mL of acetyl chloride are slowly added to a solution, magnetically stirred and kept at -40º C under argon, of 99 mg. of methyl 2-[2-(3,4,5-trimethoxyphenyl)-2-oxo-1-tosylethyl]-N-methoxymethyl-4-pyrrolecarboxylate and 0.24 mL of triethylamine in 5 mL of dry dichloromethane. After 5.7 hours 5 mL of hydrochloric acid (10%) are added and extracted with dichloromethane. Drying with sodium sulfate and concentration of the organic phase gives rise to an oil that is purified by silica gel column chromatography (15x1 cm ⊘), by elution with hexaneethyl acetate (1:1). 101 mg. of enol acetate are obtained as a mixture of isomers in a ratio of 5:1. Yield: 95 % IR (film, maximum ν): 1580. 1715, 1775. 2740, 2945, 2955, 3055, 3120 cm -1 UV (ethanol, maximum λ): 304 nm. 1 H-NMR (CDCl 3 ) (majority isomer) 2.43 and 2.42 (s, 3H, ArCH 3 and ArOCOCH 3 ), 3.12 (s, 3H, NCH 2 OCH 3 ), 3.79-374 (singlets, 6H, ArOCH 3 and ArOCH 3 ), 4.94 (d, 1H, J = 10.1 Hz, NCH 2 OCH 3 ), 5.12 (d, 1H, J = 10.5 Hz, NCH 2 OCH 3 ), 6.39 (d, 1H, J = 1.7 Hz, ArH), 7.27 (s, 2H, ArH), 7.32 (d, 2H, J = 8.4 Hz, ArH), 7.48 (d, 1H, J = 1.8 Hz, ArH), 7.70 (d, 2H, J = 8.3 Hz, ArH) ppm. EXAMPLE 4 1) Dimethyl 5-acetoxy-3,6-bis(methoxymethyl)-4-tosyl-3,6-dihydropyrrole[3,2-e]indol-1,8-dicarboxylate An aireated solution of 2.30 g. of methyl 2-[2-actoxy-2-(4-methoxycarbonyl-N-methoxymethyl-2-pyrrolyl)-1-tosylethenyl] -N-methoxymethyl-4-pyrrolecarboxylate and 160 mg. of iodine in 225 mL of ethanol, introduced in a photochemical Pyrex glass reactor, is irradiated for 3.5 hours with ultraviolet light produced by a Hanowia 400 W lamp. Addition of an aqueous saturated solution of Na 2 S 2 O 5 until the color due to the iodine disappears, followed by elimination of the ethanol under reduced pressure, extraction with dichloromethane, drying of the organic phase with sodium sulfate and elimination of the solvent, gives rise to a residue that is purified by silica gel column chromatography (19x2 cm ⊘), by elution with hexaneethyl acetate (1:1) to give 2.18 g. of the desired pyrrolindol. Yield: 95 % m.p.: 128-130º C (hexane-ethyl acetate) IR (film, maximum ν): 1720, 1790, 2950 cm -1 UV (ethanol, maximum λ): 202, 215, 237, 264, 326 nm 1 N-NMR (CDCl 3 ): 2.26 (s, 3H, ArOCOCH 3 ), 2.35 (s, 3H, ArCH 3 ). 2.96 (s, 3H, NCH 2 OCH 3 ), 3.14 (s, 3H, NCH 2 OCH 3 ), 3.82 (s, 3H, ArCO 2 CH 3 ), 3.83 (s, 3H, ArCO 2 CH 3 ), 4.97 (d, 1H, J = 10.9 Hz, NCH 2 OCH 3 ), 5.79 (m, 3H, NCH 2 OCH 3 ), 7.18 (d, 2H, J = 8.1 Hz, ArH), 7.55 (d, 2H, J = 8.3 Hz, ArH), (s, 1H, ArH), 7.96 (s, 1H, ArH) ppm. MS (e.i., m/s, %): 572 (M +. -CH 2 O, 100), 498 (M +. -CH 2 O-CH 3 OH, 49), 433 (M +. -CH 3 (C 6 H 4 )SO, 33), 402 (M +. -CH 3 (C 6 H 4 )SO-CH 3 O, 67), 375 (M +. -CH 2 CO-CH 3 (C 6 H 4 )SO 2 , 67), 343 (M +. CH 2 CO-CH 3 (C 6 H 4 )SO 2 -CH 3 OH. 38), 139 (CH 3 (C 6 H 4 )SO + , 29), 91 (CH 3 (C 6 H 4 ) + , 23). 2) Methyl 5-acetoxy-8-methoxy-N-methoxymethyl-4-tosylbenzo [e] indole-1-carboxylate An aerated solution of 560 mg. of methyl 2-[2-acetoxy-2-(4-methoxyphenyl)-1-tosylethenyl]-N-methoxymethyl-4-pyrrolecarboxylate and 40 mg. of iodine in 100 mL of ethanol introduced in a photochemical Pyrex glass reactor, is irradated for 17 hours with ultraviolet light produced by a Hanowia 400 W lamp. Addition of an aqueous saturated solution of Na 2 S 2 O 5 until the color due to the iodine disappears, followed by elimination of the ethanol under reduced pressure, extraction with dichloromethane, drying of the organic phase with sodium sulfate and elimination of the solvent gives rise to a residue that is purified by silica gel column chromatography (23x1 cm ⊘), by elution with hexane-ethyl acetate (1:1) to give 457 mg. of the desired pyrrolindol. Yield: 82% m.p.: 163-164º C IR (KBr, maximum ): 1510, 1620, 1710, 1780, 2950, 3120 cm -1 UV (ethanol, maximum λ): 216, 272, 326 nm 1 H-NMR(CDCl 3 ): 2.37 (s, 3H, ArCH 3 ), 2.39 (s, 3H, ArOCOCH 3 ) , 2.95 (s, 3H, ArCH 2 OCH 3 ), 3.95 (s, 3H, ArCO 2 CH 3 ), 4.06 (s, 3H, ArCO 2 CH 3 ) 5.86 (s, 2H, ArCH 2 OCH 3 ), 7.13 (dd, 1 H, J = 2.5 and 9.2 Hz, ArH), 7.2 (d, 2H, J= 8.2 Hz, ArH), 7.59 (d, 2H, J = 8.2 Hz, ArH), 7.60 (s, 1H, ArH), 8,24 (s, 1H, ArH), 9.42 (d, 1H, J=2.5 Hz, ArH) ppm MS (e.i., m/s, %): 511 (M + , 11), 469 (M +. -CH 2 CO, 100), 437 (M +. -CH 2 CO-CH 3 OH, 35), 315 (M +. -CH 2 CO-Ts. 40), 139 (CH 3 (C 6 H 4 )SO +. , 26), 91 (CH 3 (C 6 H 4 ) +. , 12). 3) Methyl 5-acetoxy-7,8,9-trimethoxy-N-methoxymethyl-4-tosylbenzo [e] indol-1-carboxylate An aireated solution of 101 mg. of methyl 2-[2-acetoxy-2-(3,4,5-trimethoxyphenyl)-1-tosylethenyl]-N-methoxymethyl-4-pyrrolecarboxylate and 9 mg. of iodine in 30 mL of ethanol, introduced in a photochemical Pyrex glass reaction, is irradiated for 2.6 hours with ultraviolet light produced by a Hanowia 400 W lamp. Addition of an aqueous saturated solution of Na 2 S 2 O 5 until the color due to the iodine disappears, followed by elimination of the ethanol under reduced pressure, extraction with dichloromethane, drying of the organic phase with sodium sulfate and elimination of the solvent, gives rise to a residue that is purified by silica gel column chromatography, by elution with a dichloromethaneethyl acetate gradient, increasing the proportion of ethyl acetate from 0 to 10%, to give 32 mg. of the desired pyrroleindol. Yield: 32 % UV (ethanol, maximum λ): 228, 256, 336 nm. 1 H-NMR (CDCl 3 ): 2.39 (s, 6H, NCH 2 OCH 3 and ArCH 3 ), 2.95 (s, 3H, ArOCOCH 3 ), 3.73 (s, 3H, ArOCH 3 ), 3.84 (s, 3H, ArOCH 3 ), 3.90 (s, 3H, ArCO 2 CH 3 ), 4.06 (s, 3H, ArOCH 3 ), 5.84 (s, 2H, NCH 2 OCH 3 ), 6.79 (s, 1H, ArH), 7.25 (d, 2H, J = 8.5 Hz, ArH), 7.67 (d, 2H, J = 8.4 Hz, ArH), 7.74 (s, 1H, ArH) ppm.

Claims: A preparation method of areno [e] indols, useful as intermediates in the synthesis of products with antitumoral activity, of formula: wherein: -Ar represents phenyl or substituted phenyl -Ar' represents a condensed radical of formulae: wherein R, R 1 , R 2 , R 3 represent a hydrogen, a halide, a linear or branched alkyl, alkenyl or alkynyl radical, a formyl, acyl, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, hydroxy, alkoxy, amino, alkylamino, dialkylamino, acylamino or nitro radical; and X represents a substituted or unsubstituted nitrogen; whose method is characterized in that is comprises the following steps: a) reacting a compound of general formula (VI): wherein Ar represents phenyl or substituted phenyl, with a strong base in an inert solvent and then with an aldehyde of formula Ar''-CHO wherein Ar'' represents a phenyl, pyrrolyl, furanyl or thiophenyl group substituted up to three times by any of the above cited radicals for R, R 1 , R 2 and R 3 , obtaining as a reaction product a compound of general formula: wherein Ar and Ar'' have the meaning given above; b) oxidizing the compounds of general formula (VII) obtained in step a) in an inert solvent to obtain the corresponding ketone of general formula: wherein Ar and Ar'' have the meaning given above; c) reacting the ketone of general formula (VIII) of step b) with a strong base in a suitable solvent and then with acyl chloride of general formula ClCOR obtaining products of general formula: wherein Ar, Ar'' and R have the meaning given above; d) subjecting the compounds of general formula (IX) obtained in step c) to a photochemical cycling process in an organic solvent in the presence of an oxidant and source of ultraviolet light, finally obtaining compounds of general formula (I). A method according to claim 1, for preparing areno [e] indols of the following structural formula: wherein R represents an acyl group of 2 to 5 linear or branched chain carbon atoms and Ar represents phenyl or substituted phenyl. A method according to claim 1, for preparing areno [e] indols of the following structural formula: wherein R represents an acyl group of 2 to 5 linear or branched chain carbon atoms and Ar represents phenyl or substituted phenyl. A method according to claim 1, for preparing areno [e] indols of the following structural formula: wherein R represents an acyl group of 2 to 5 linear or branched chain carbon atoms and Ar represents phenyl or substituted phenyl. Method according to claim 1, characterized in that in step a) the base used in an alkaline amide, alkyllithium or aryllithium; the inert solvent is dialkyl ether, 1,4-dioxane or tetrahydrufuran; the reaction time is between 0.5 and 5 hours and the reaction temperatures between -80 and 0º C. Method according to claim 5, characterized in that the base used is lithium diisopropylamide and the aromatic aldehyde is methyl 2-formyl-N-methoxymethyl-4-pyrrolecarboxylate, 4-methoxybenzldehyde or 3,4,5-trimethoxybenzaldehyde. Method according to claim 1, , characterized in that in step b) the oxidant used is 2,3-dicyano-5,6-dichloro-p-benzoquinone; the inert solvent is an aromatic solvent or 1,4-dioxane; the reaction time is between 7 and 24 hours and the reaction temperature is between room temperature and the reflux temperature of the solvent. Method according to claim 7, characterized in that the aromatic solvent used is benzene, toluene, xylene or chlorobenzene. Method according to claim 1, characterized in that in step c) the base used is am amine, an alkaline amide, an alkyllithum or an aryllithium; the inert solvent is chloroform, dichloromethane or 1,2-dichloroethane; the acylating agent is an acid chloride of 2 to 5 linear or branched chain carbon atoms; the reaction time is between 1 and 6 hours and the temperature between -50º C and room temperature. Method according to claim 9, characterized in that the base is triethylamine, the solvent is dichloromethane, the acylating agent is acetyl chloride and the tempeature is -40º C. Method according to claim 1, , characterized in that in step d) the solvent is an alcohol with a low molecular weight; the oxidant is oxygen associated to catalytic iodine; the reaction temperature is between room temperature and the boiling point of the solvent and the reaction times are between 1 and 19 hours. Method according to claim 11, characterized in that the solvent is ethanol. Method according to claim 1, characterized in that the compound of formula (VI) used as a starting product in step (a) is obtained, in turn, by means of the following steps: a) reacting the methyl 2-formyl-4-pyrrolecarboxylate with chloromethyl methyl ether in the presence of a base and a suitable organic solvent, obtaining as a reaction product methyl 2-formyl-N-methoxymethyl-4-pyrrolecarboxylate; b) reducing the methyl 2-formyl-N-methoxymethyl-4-pyrrolecarboxylate obtained in step a) with a metal hydride in an organic solvent to obtain methyl 2-hydroxymethyl-N-methoxymethyl-4-pyrrolecarboxylate; c) reacting the methyl 2-hydroxymethyl-N-methoxymethyl-4-pyrrolcarboxylate obtained in step b) with a substituted or unsubstituted benzenesulfinate in an acid medium to finally obtain the compounds of general formula (VI). Method according to claim 13, characterized in that in step (a) the base used is an alkoxide, a tertiary amine, an alkaline amide or an organollithic compound; the organic solvent is an aprotic dipolar solvent, a hydrocarboned solvent or ether; the reaction time is between 1 and 40 hours and the temperature is between -10 and 50º C. Method according to claim 14, characterized in that the base used is potassium tert-buthoxide and the organic solvent is N,N-dimethylformamide. Method according to claim 15 characterized in that in step b) the metal hydride is boron hydride and the organic solvent is an alcohol with a low molecular weight such as methanol or ethanol. Method according to claim 16, characterized in that the boron hydride is sodium borohydride; the organic solvent is methanol; the reaction temperature is between 0 and 40º C and the reaction time is between 0.5 and 3 hours. Method according to claim 13, characterized in that in step c), the substituted or unsubstituted benzenesulfinate is p-toluenesulfinate; the contra-cation of the sulfinate is a metal cation and the acid medium is comprised of an organic acid used as a solvent. Method according to claim 18, characterized in that the contra-cation of the sulfinate is the sodium cation; the organic acid used as a solvent is aqueous formic acid 85%; the reaction temperature is between 0 and 50º C and the reaction time is between 0.5 and 3 days. An 1-aryl-2-pyrrolylethylene derivative useful in the preparation of areno [e] indols of formula: wherein: -Ar represents phenyl or substituted phenyl - Ar' represents a condensed radical of formulae: wherein R, R 1 , R 2 , R 3 can represent a hydrogen, a halogen, a linear or branched alkyl, alkenyl or alkynyl radical, a formyl, acyl, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, hydroxy, alkoxy, amino, alkylamino, dialkylamino, acylamino or nitro radical; and X represents oxygen, sulfur or substituted or unsubstituted nitrogen, the derivative having the formula wherein Ar, Ar'' and R have the meaning given above. Derivative according to claim 20, characterized in that R represents an acyl group of 2 to 5 linear or branched chain carbon atoms and Ar represents phenyl or substituted phenyl. A method for preparing a derivative according to claim 20, characterized in that is comprises the following steps: a) reacting a compound of general formula (VI): wherein Ar represents phenyl or substituted phenyl, with a strong base in an inert solvent and then with an aldehyde of formula Ar''-CHO wherein Ar'' represents a phenyl, pyrrolyl, furanyl or thiophenyl group substituted up to three times by any of the above cited radicals for R, R 1 , R 2 and R 3 , obtaining as a reaction product a compound of general formula: wherein Ar and Ar'' have the meaning given above; b) oxidizing the compounds of general formula (VII) obtained in step a) in an inert solvent to obtain the corresponding ketone of general formula: wherein Ar and Ar'' have the meaning given above; c) reacting the ketone of general formula (VIII) of step b) with a strong base in a suitable solvent and then with acyl chloride of general formula ClCOR. Method according to claim 22, characterized in that in step a) the base used in al alkaline amide, alkyllithium or aryllithium; the inert solvent is dialkyl ether, 1,4-dioxane or tetrahydrufuran; the reaction time is between 0.5 and 5 hours and the reaction temperatures between -80 and 0º C. Method according to claim 23, characterized in that the base used is lithium diisopropylamide and the aromatical aldehyde is methyl 2-formyl-N-methoxymethyl-4-pyrrolecarboxylate, 4-methoxybenzldehyde or 3,4,5-trimethoxybenzaldehyde. Method according to claim 22, characterized in that in step b) the oxidant used is 2,3-dicyano-5,6-dichloro-p-benzoquinone; the inert solvent is an aromatic solvent or 1,4-dioxane; the reaction time is between 7 and 24 hours and the reaction temperature is between room temperature and the reflux temperature of the solvent. Method according to claim 25, characterized in that the aromatic solvent used is benzene, toluene, xylene or chlorobenzene. Method according to claim 22, characterized in that in step c) the base used is am amine, an alkaline amide, an alkyllithum or an aryllithium; the inert solvent is chloroform, dichloromethane or 1,2-dichloroethane; the acylating agent is an acid chloride of 2 to 5 linear or branched chain carbon atoms; the reaction time is between 1 and 6 hours and the temperature between -50º C and room temperature. Method according to claim 27, characterized in that the base is triethylamine, the solvent is dichloromethane, the acylating agent is acetyl chloride and the tempeature is -40º C. Method according to claim 22, characterized in that the compound of formula (VI) used as a starting product in step (a) is obtained, in turn, by means of the following steps: a) reacting the methyl 2-formyl-4-pyrrolecarboxylate with chloromethylmethylether in the presence of a base and a suitable organic solvent, obtaining as a reaction product methyl 2-formyl-N-methoxymethyl-4-pyrrolecarboxylate; b) reducing the methyl 2-formyl-N-methoxymethyl-4-pyrrolecarboxylate obtained in step a) with a metal hydride in an organic solvent to obtain methyl 2-hydroxymethyl-N-methoxymethyl-4-pyrrolcarboxylate; c) reacting the methyl 2-hydroxymethyl-N-methoxymethyl-4-pyrrolecarboxylate obtained in step b) with a substituted or unsubstituted benzenesulfinate in an acid medium to finally obtain the compounds of general formula (VI.) Method according to claim 29, characterized in that in step (a) the base used is an alkoxide, a tertiary amine, an alkaline amide or an organolithic compound; the organic solvent is an aprotic dipolar solvent, a hydrocarboned solvent or ether; the reaction time is between 1 and 40 hours and the temperature is between -10 and 50º C. Method according to claim 30, characterized in that the base used is potassium tert-buthoxide and the organic solvent is N,N-dimethylformamide. Method according to claim 29, characterized in that in step b) the metal hydride is boron hydride and the organic solvent is an alcohol with a low molecular weight such as methanol or ethanol. Method according to claim 32, characterized in that the boron hydride is sodium borohydride; the organic solvent is methanol; the reaction temperature is between 0 and 40º C and the reaction time is between 0.5 and 3 hours. Method according to claim 29, characterized in that in step c), the substituted or unsubstituted benzenesulfinate is p-toluenesulfinate; the contra-cation of the sulfinate is a metal cation and the acid medium is comprised of an organic acid used as a solvent. Method according to claim 34, characterized in that the contra-cation of the sulfinate is the sodium cation; the organic acid used as a solvent is aqueous formic acid 85%; the reaction temperature is between 0 and 50º C and the reaction time is between 0.5 and 3 days.

Inventors: ALEXANDER KOEN, DELAMANO GARCIA JOSE, GARCIA GRAVALOS DOLORES, SAS BENEDIKT, TOJO SUAREZ GABRIEL, ALEXANDER, KOEN, DELAMANO GARCIA, JOSE, GARCIA GRAVALOS, DOLORES, SAS, BENEDIKT, TOJO SUAREZ, GABRIEL, DELAMANO GARCIA, José
Applicants: PHARMA MAR S A PHARMAR, PHARMA-MAR S.A.-PHARMAR
Application year: 1993
Main classification: C07D487
IPC codes: C07D491, C07D495, C07D207, C07D487, C07D209