CA 02298677 2000-O1-31 WO-99/U6388 PCT/GB98/02317 1 PHARMACEUTICAL COMPOUNDS ISOLATED FROM ARISTOLOCHIA TALISCANA FIELD OF THE INVENTION This invention relates to compounds derived from the plant Aristolochia taliscana and their analogues, and the uses of such compounds in medicine. BACKGROUND OF THE INVENTION Aristolochia taliscana, a climbing shrub found in the jungles of the southern coastal region of Mexico, is part of a family of climbing herbs and shrubs called Aristolochiaceae, numbering about six hundred species divided into eleven genera, and found mostly in tropical and sub-tropical regions. It is believed that the species Aristolochia taliscana is found only in Mexico. Members of the Aristolochiaceae are known for their ability to synthesise phenanthrene alkaloids, and in particular the aristolactam alkaloids and the aristolochic acids, and arylpropanoid compounds such as the lignans and neolignans. Such compounds are disclosed in, for example, R. Hegnauer "Chemotaxonomie der Pflanzen", Vol. Ill, pp 184-199, Birkhauser Verlag, Basel and Stuttgart, 1964; R. Hegnauer "Chemotaxonomie der pflanzen", Vol. VII, pp 75- 83, Birkhauser Verlag, Basel - Boston - Berlin, 1989 and F.E. Correa et aL"Especies Vegetates Promisorios", Vol. I, pp 440-469, Secretaria Ejecutiva del Convenio Andies Beilo (SECAB), Bogota D.E. 1989, Colombia and Lopes etal. Rev. Latinoam. Quim.,19 (3-4), 1 13-17, 1988. In Lopes etaL, for example, the isolation of lignans from a number of different Aristolochiaceae is described and it is disclosed that such compounds are reported as having anti-tumour, antifungal, antibacterial and insecticidal activity. In Hinou etal., J. Crude Drug Research, 1990, 28(2), 149-51, it is disclosed that aristolactam and aristolochic acid compounds isolated from Aristolochia longs have antibacterial activity and cytotoxic activity against P-388 lymphocytic leukaemia and human bronchial epidermoid carcinoma cells. CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 2 The isolation and characterisation of lignans, neolignans and related compounds from a wide variety of plant species has been reviewed in a series of articles by R.S. Ward, see for example Natural Product Reports, 1985, Vol. 5 pp 203-206; 1990, Vol. 7, pp 356-363; 1993, Vol. 10, pp 1-23. However, it is clear from the available literature that the chemical structures and concentrations of arylpropanoid compounds found in Aristolochiaceae vary widely from one. species to another. For example, in Lopes etal. (idem.), reference is made to the extraction of four Brazilian species of Aristolochiaceae, from which a number of dibenzyl-butyrolactone type lignans and furofuran type lignans were isolated. From studies made by the present inventors, such compounds would appear to be absent from Aristolochia taliscana. Much of the work carried out on the Aristolochiaceae has focused on the phenanthrene alkaloid content, and in particular the aristolactam alkaloids found in the plants - see for example Crohare et al. Phytochemistry, 1974, Vol. 13, 1957- 1962, Priestap, Phytochemistry, 1985, Vol. 24, 849-852, Talapatra et al. Phytochemistry, 1988, Vol. 27, 903-906 and Houghton et al. Phytochemistry, 1991, Vol. 10, 253-254. Houghton et al. suggest that compounds such as aristolochic acid, the ring-opened form of aristolactam, are of interest as immunostimulants and anticancer agents. Crude extracts from Arisiolochia taliscana have been known for many years to have certain medicinal properties. A book published in the 1800's, called "Las Plantas Medicinales de Mexico" (Medicinal Plants of Mexicol makes reference to the use of Aristolochia taliscana extracts in the treatment of snake bites and it would appear that the native tribes in this region of Mexico have known about the uses of the extracts for many centuries. In US Patent No. 4782077 it is disclosed that an alkaloid (referred to as taliscanin) extracted from the root ofAristolochia taliscana, alleviates the symptoms of Parkinsonism and related neurological disorders. It is also indicated in US 4782077 that the alkaloid taliscanin may be useful in the treatment of various other neurological disorders, including Alzheimer's disease, impotency, and neurological CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 3 disorders associated with viral, bacterial, fungal and parasitic infections. In US 4782077, an extract was prepared by pulverising Aristolochia taiiscana root and subjecting the powder to soxhlet extraction with hexane and then benzene followed by column chromatography on an alumina column eluting with benzene-ether mixtures. The known aristolactam alkaloid taliscanin, was characterised on the basis of its melting point (272.degree.-273.degree.C) and its spectroscopic data However, the aristolactam alkaloid taliscanin has since been tested for its ability to interact with neurotransmitter receptors, and, somewhat surprisingly, exhibited 50% inhibition in only one receptor (the opiate mu receptor) out of twenty seven common receptor types tested, and exhibited very poor levels of inhibition with the remaining receptors. In particular, taliscanin exhibited negligible activity at the dopamine, GABA and serotonin receptors. These results suggest either that taiiscanine exerts its neurological effects by a mechanism which is of a currently unknown type (which seems unlikely) or, perhaps, that there is another active principle in Aristolochia taiiscana which is responsible for the reported activities. SUMMARY OF THE INVENTION The present applicants have been able to separate and identify the components of Aristolochia taliscana extracts and have found that the extract contains a substantial number of compounds other than aristolactams, in particular certain benzofuran neolignans, many of which are novel. Compounds found in the extracts have been found to have biological properties indicative of therapeutic utility. For example, benzofuran compounds isolated from taliscanine have been tested and have been-found to be active as anti-mutagenic agents, as cytotoxic agents, and some have been found to have good antifungal activity. On this basis, it is anticipated that the compounds in question will find use in the treatment of tumours and other neoplastic diseases, as well as fungal infections. Accordingly, in a first aspect, the invention provides the use of an extract of Aristolochia taliscana or one or more anti-mutagenically active components CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 4 isolable therefrom for the manufacture of a medicament for the treatment of disease states mediated by mutagenesis. The invention also provides the use of an extract of an Aristolochia species, preferably Aristolochia taliscana or one or more component compounds isolable therefrom, for the manufacture of a medicament for the treatment of chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, synovitis and_ psoriasis. As indicated above, component compounds of Aristolochia taliscana have also been found to have good antifungal activity, and in a still further aspect, the invention provides the use of an extract of Aristolochia taliscana or one or more antifungally active compounds isolable therefrom for the manufacture of a composition for antifungal use, for example in the treatment of plants or animals. The invention also provides pharmaceutical compositions comprising benzofuran compounds of the type found in Aristolochia taliscana or benzofuran compounds analogous thereto, for example benzofuran compounds in which an aryl ring (such as an oxygenated phenyl ring) is attached to the heterocyclic ring of the benzofuran, and the uses of such compounds in medicine. The invention also provides a novel group of benzofuran compounds having an oxygenated aryl ring (such as an oxygenated phenyl ring) attached to the heterocyclic ring of the benzofuran. DESCRIPTION OF PREFERRED EMBODIMENTS Compounds for use . in Medicine - New Medical Uses of Known and Novel Compounds In one preferred aspect, the invention provides the use of a compound for the manufacture of a medicament for use in any one or more of the therapeutic uses selected from the treatment of neoplastic diseases or diseases mediated or initiated by mutagenesis or abnormal cellular proliferation, or as a cytotoxic agent, or the treatment of chronic inflammatory conditions; the compound being of the CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 formula (I): m 111 wherein the dotted line signifies a single or double bond; n is 0, 1, 2 or 3; A is a monocyclic aryl ring containing up to two heteroatoms and being optionally substituted by one or more substituent groups which may be the same or different and are selected from R'0, R', R'S, halogen; aryl and heteroaryl, wherein R3 is hydrogen, or a hydrocarbyl group optionally substituted by a hydroxy or hydrocarbyloxy group; B is selected from carboxy, carboxaldehyde, hydrocarbyl and hydrocarbyloxy groups wherein the hydrocarbyl group is acyclic or cyclic, and optionally contains one or more heteroatoms, and is optionally substituted by one or more hydroxy, alkoxy, alkenyloxy, alkynyloxy, aryloxy, aldehyde, alkanoyl, acetal, hemiacetal and carboxy groups; R' is hydrogen or a hydrocarbyl group optionally including one or more heteroatoms and optionally substituted by one or more substituents selected from hydroxy, hydrocarbyfoxy and aryl groups; and RZ is hydroxy or a hydrocarbyl or hydrocarbyloxy group optionally substituted by one or more substituents selected from hydroxy, hydrocarbyloxy and aryl groups. It is preferred that the monocyclic aryl ring A is attached to the 2-position of the furan ring, and it is particularly preferred that the aryl ring is a phenyl group. The phenyl ring can contain up to five substituent groups but preferably contains no more than three substituents. Preferably. the group B is attached to the 5-position of the benzofuran group. Preferably, there is only one group R2, which is attached to the 7-position of the benzofuran ring. Preferably, the dotted line signifies a double bond. CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 6 In a particularly preferred embodiment, the invention provides the use of a compound for the manufacture of a medicament for use in the treatment of the conditions described above in relation to formula (1), the compound having the formula 111): B wherein the dotted line signifies a single or double bond, B, R' and Rz are as hereinbefore defined, R4 and R5 are the same or different and each is selected from hydrogen, C,_zo hYdrocarbyl, Cs_zo aryl, or Cs_zo oxygen-containing heteroaryl; R6 is selected from hydrogen, halogen, C,_2o hYdrocarbyl or C,_zo hydrocarbyloxy optionally substituted by one or more hydroxy, alkoxy or aralkyloxy groups; or R6 is Cs_zs aryl or oxygen or nitrogen-containing heteroaryl. One preferred group of compounds are the compounds in which B is C,.e alkyl or alkenyl optionally substituted by one or more substituents selected from hydroxy, CHO, or R'0 wherein R' is a C,_s alkyl or alkenyl group. More preferably, the group B is selected from CH = CHCH3, CH2CH = CHz, CH/OH)CH = CHz, CH=CHCHO, CHO, CH=CHCH20H and CH(OH)CH(OH)CH3. A particularly preferred group B is CH =CHCH3. In compounds of the formula 111) R' and Rs are preferably selected from hydrogen, or C,.6 alkyl, or R4 and Rs together define an alkylene group such as -CHZ Preferably, at least one of R4 and R5 is hydrogen. Particularly preferred compounds are those in which the dotted line signifies a double bond and one of R4 and Rs is hydrogen. Examples of groups R6 are hydrogen, halogen (e.g. fiuoro, chloro, bromo or CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 7 iodo), C,_s alkoxy (e.g. methoxy), a 2-benzofuranyl ring, or an aristolactam group. In the foregoing formulae (I) and III), examples of hydrocarbyl groups are aliphatic, alicyclic and aromatic groups such as alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, cycfoalkenyl, cycfoalkenylalkyl, cycloalkenylalkenyl, aryl, aralkyl, arafkenyl, aralkynyl. The hydrocarbyl groups can be optionally interrupted by one or more heteroatoms such as oxygen and sulphur. Particular examples of alkyl groups are C,_s alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl and t-butyl. Examples of cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicycioheptanyl, decalinyl, adamantyl, norbornyl and bicyclooctyl. Examples of alkenyl and alkynyl groups include vinyl, ethynyl, allyl, 1- propenyl, propargyi, but-1-enyl, but-2-enyl, but-3-enyl and 3-methylbutenyl. Examples of cycloalkenyl groups are cyclopentenyl, cyclohexenyl, cycloheptenyl, and monocyclic, bicyclic and tricyclic terpene groups. Examples of aryl groups are phenyl and naphthyl. Examples of phenylalkyl and phenylalkenyl groups are benzyl, phenethyl, phenylpropyl, phenylbutyl and styryl groups. First Medical Uses of Compounds Not Previously Disclosed As Having Therapeutic Utility Many compounds of the formulae (1) and 111) have not previously been disclosed as having any therapeutic uses. Accordingly, in another embodiment, the invention provides a compound of the formula (1) or (11) as hereinbefore defined for use in medicine, for example for use in any one or more of the therapeutic uses selected from the treatment of neoplastic diseases or diseases mediated or initiated by mutagenesis or abnormal cellular proliferation, or as a cytotoxic agent, or the CA 02298677 2000-O1-31 WO-99/06388 PCT/GB98/02317 8 treatment of chronic inflammatory conditions, or as an anti-fungal agent in the treatment of plants or animals; but provided that when R' is 3-methyl, RZ is a single methoxy group at the 7-position, and either (i) the furan ring is unsaturated and is substituted at the 2-position with a 4-hydroxy-3-methoxyphenyl group or a 3,4- methylenedioxyphenyl group; or iii) the furan ring is a 2,3-dihydrofuran ring and is substituted at the 2-position with a 4-hydroxy-3-methoxyphenyl group, then B is other than a prop-1-enyl group attached to the 5-position of the benzfuran ring. Novel Compounds ner se The present invention also provides novel compounds per se of the formula O R1' wherein R" is hydrogen or C,_s alkyl; R'2 is selected from hydrogen, C,_B alkyl; a cyclic terpenoid group or a group of the formula E, G or J; R'3 is selected from hydrogen; C,_3 alkyl or hydroxy-C,_3 alkyl; R'4 is selected from CH = CH-CH3, CH (OH)CH = CH2, CH = CH-CHO, CH = CH- CHzOH, CH(OH)CH(OR")CH3, or a group L; R'S is hydrogen or C,_8 alkyl; R'B is hydrogen, a group M or an aristolactam group; and R" is hydrogen or a group T; wherein the groups E, G, L, J, M and T are represented by the formulae: CA 02298677 2000-O1-31 WO '99/06388 PCT/GB98/02317 9 7 CH(OH) CH(CH3)-"f CH(CH,) '~ CH(OH) RIO OR'' O Rl (E) (G) H$C CH3 , W ss OR i ORS R~. ORy ORz (L) (J1 ,13 (M) (T) OR and pharmaceutically acceptable salts thereof; provided that when R", R'3 and R'S are all methyl,and R'z and R'e are both hydrogen, R'4 is selected only from CH(OH1CH=CH2, CH=CH-CHO, CH=CH-CH20H, CH(0H)CHfOR"lCH3where R" is a group T, or a group L. In one particular embodiment, there is provided a novel compound of the CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 formula 11V): (IV) wherein R", R'Z, R'3 R'.degree., R'S and R" are as hereinbefore defined and X is a group: R2Q R Rs R R wherein R'e is hydrogen, benzyl or C,_s alkyl; R'9 to R24 are the same or different and are selected from hydrogen, hydroxy, C,_6 alkoxy, C,_s alkyl and hydroxy-C,,6 alkyl; or any two adjacent groups together form an alkylene dioxy group. In another embodiment, the invention provides novel compounds of the formula (V): ~,3 Rs~ w i I OR wherein Y is a monocyclic or bicyclic terpenoid group and in particular a group of the structure: OR''~ ' CA 02298677 2000-O1-31 WO-99/06388 PCT/GB98/02317 11 HrCH3 H CH~CH3)a Tetralone Compounds In a further aspect, the invention provides tetralone compounds for use in medicine, the tetralone compounds being of the formula (VI): O OH R~O wherein R2s and RZ' are the same or different and each is C,.s alkyl, or R25 and RZs together form an alkylene group (such as methylene); and RZS is hydrogen or C,_s alkyl. Preferably R25, RZS and RZ' are all methyl. Tetralone compounds of the formula (Vl) have biocidal activity, and in particular cytotoxic, antibacterial and antifungal activity. It is therefore anticipated that they will be useful in the treatment of proliferative and infective diseases and conditions such as cancers and bacterial and fungal infections. Accordingly, the invention also provides a compound of the formula (VI) for use in the treatment of bacterial or fungal infections, or for use in the treatment of cancers and other proliferative diseases such as psoriasis. CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 12 Compounds of the formula (VI) have previously been reported as synthetic intermediates (see Joie et al. Chem. Pharm. Bull. 38, 1851-56 (1990). Particular novel compounds of the invention are: ( ~ )-5-( 1 -Hydroxyallyi)-2-(4-hydroxy-3-rnethoxyphenyl)-7-methoxy-3- methylbenzofuran (Compound 9); 2-(4-Hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxy-5-IE)- propenylbenzofuran (Compound 10); 2-(4-Hydroxy-3-methoxyphenyl)-7-methoxy-3-methyl-5-[(E)-3- oxopropenyl]benzofuran (Compound 11 ); 5-Formyl-3-14-hydroxy-3-methoxyphenyl)-7-methoxy-3-methylbenzofuran (Compound 12); 2-(4-Hydroxy-2-methoxyphenyl)-5-[(EI-3-hydroxypropenyl]-7-methoxy-3- methylbenzofuran (Compound 13); 2-(3,4-Dihydroxyphenyl)-7-methoxy-3-methyl-5-(E)-propenylbenzofuran (Compound 14); erythro-5-(1,2-Dihydroxypropyl)- 2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-3- methylbenzofuran (Compound 15); (2R,3R)-2,3-Dihydro-2-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxy-5- (E)-propenylbenzofuran (Compound 19); erythro-1-(4-Acetoxy-3-methoxyphenyl)-2-[4-(7-methoxy-3-methyl-5-(E)- propenylbenzofuran-2-yl)-2-methoxyphenoxy]propylacetate (Compound 221; threo-1 -(4-Acetoxy-3-methoxyphenyl)-2-[4-(7-methoxy-3-methyl-5-(E)- propenylbenzofuran-2-yl)-2-methoxyphenoxy]propyl-acetate (Compound 23); threo-1-[2-(4-Hydroxy-3-methoxyphenyl)-7-methoxy-3-methylbenzofuran-5-yl]-2-[4- (3-methyl-5-(e)-propenylbenzofuran-2-yl)-2-methoxyphenoxy]propan-1-of (Compound 24); 2-Methoxy-4-[7-me thoxy-3-methyl-5-(E)-propenylbenzofuran-2-yl]-6-E4-(7- methoxy- 3-methyl-5-(E)-propenylbenzofuran-2-yl)-2-methoxyphenoxy]phenol (Compound 25) $.2',9.3'-Tetrahydro-bis-eupomatenoid-7 (Compound 26); 15-(Aristolactam-I-9-yl)-eupomatenoid-7 (Compound 27); 14-0-a-Cadinyl-eupomatenoid-7 (Compound 28); and (2R,4S1-2-HYdroxy-6-methoxy-4,7-dimethyl-1-tetralone (Compound 34). CA 02298677 2000-O1-31 WQ 99/OG388 PCT/GB98/02317 13 Extraction of Compounds From Aristolochia taliscana Certain compounds of the formulae I to VI can be obtained by solvent extraction of plant material, such as roots, bark, leaves and twigs, from Aristolochia ialiscana using solvents such as benzene followed by chromatographic separation of the components of the solvent extract. A typical extraction protocol is described in detail below. Synthesis of Compounds of the Formulae I to V The compounds of the invention, whether naturally occurring or synthetic analogues thereof can be synthesized from readily available starting materials by synthetic methods well known to those skilled in the art. For example, compounds of the formulae (I) or (II) can be prepared by means of the reaction scheme set out in Figure 1. The reaction conditions and reagents employed in the scheme set out in Figure 1 can be substantially as described in M. Watanabe etal. Chem. Pharm. Bull. 37, 2884 (1989); ibid. 38, 41 (1990), and ibid. 39, 3123 (1991 ), the contents of which are incorporated herein by reference. An alternative synthetic scheme applicable to compounds of the formulae (I) or (II) wherein R' is a methyl group attached to the 3-position of the furan ring and A is an aryl group attached to the 2-position of the furan ring, is set out in Figure 2. In the reaction-scheme shown in Figure 2, the methoxymethylaryl ketone is reacted with the substituted o-hydroxybenzaldehyde in an acidic medium (for example a mixture of hydrochloric acid and acetic acid) to give a benzpyryllium salt which is then subjected to oxidation and rearrangement in the presence of hydrogen peroxide and methanol at pH 5.8 to give a benzfuran 3-carboxy ester. The benzfuran 3-carboxyester can then be treated successively with (i) lithium aluminium hydride in an ether such as diethyl ether; (ii) manganese dioxide in a non- CA 02298677 2000-O1-31 WO~ 99/06388 PCT/GB98/02317 14 polar solvent such as benzene; (iii) 1,2 ethylene-dithiol, acetic acid and boron trifluoride etherate; and (iv) Raney nickel in an alcohol such as ethanol. The general conditions under which each of the above reactions can be carried out are disclosed in McCredie et al., Austral. J. Chem. 22, 101 1 (19691, the contents of which are incorporated herein by reference. Pharmaceutical Uses The extracts and compounds of the invention are useful in a number of medical aspects. In use as therapeutic agents, the compounds or extracts can be administered in standard manner, for example orally, parenterally, transdermally, rectally, via inhalation or via buccal administration. Preferably, however, they are administered orally. The dosage employed will depend on the nature and purity of the extract and the concentrations of the active principles. For an extract that has not been fractionated, the concentration administered can be in the range from 0.5mg to 500mg (dry weight) of extract per patient per day, more usually 1 mg to 1 OOmg per day. If an isolated compound or synthetic analogue thereof, or mixture of such compounds is employed, the dosages of such compounds administered typically will be similarly in the range 0.5mg to 500mg per patient per day, more usually 1 mg to 1 OOmg per day. The extracts or compounds rnay be administered as single doses or multiple doses as desired. The dosages of the extracts or compounds of the invention administered will depend upon inter alia the potency of the extract or compound, and the nature and severity of the disease state or condition under treatment but ultimately, however, will be at the discretion of the physician. Pharmaceutical Formulations The extracts and compounds of the invention can be formulated as solutions, syrups, tablets, capsules, lozenges, inserts, patches, powders, pills, solutions for injection or drops, or aerosols such as dry powder aerosols or liquid aerosols, by way of example. Such formulations can be prepared in accordance with methods well known per se. In a particular embodiment, the compositions of the invention can take the CA 02298677 2000-O1-31 WO-99/06388 PCT/GB98/02317 form of solid or semi-solid unit dosage form. For example, the compositions can take the form of tablets, granules, lozenges or capsules. A solid or semi-solid dosage form according to the present invention can contain, for example, from l0mg to 1000mg of the extract or compounds of the invention, more typically 50mg to 500mg, e.g. 100mg to 400mg, and in particular 150mg to 350mg, particular unit dosages being approximately 200mg and 300mg. A tablet composition will typically contain one or more pharmaceutically acceptable solid diluents, examples of which include sugars such as sucrose and lactose, and sugar alcohols such as xylitol, sorbitol and mannitol; lactose and sorbitol being particular examples. The tablets will also typically contain one or more excipients selected from granulating agents, binders, lubricants and disintegrating agents. Examples of disintegrants include starch and starch derivatives, and other swellable polymers, for example cross-linked polymeric disintegrants such as cross- linked carboxymethylcellulose, cross-linked polyvinylpyrrolidone and starch glycolates. Examples of lubricants include stearates such magnesium stearate and stearic acid. A capsule composition typically will comprise an outer shell or casing which may, for example, be formed from hard or soft forms of gelatin or gelatin- equivalents in conventional fashion. The outer shell is filled with an extract or a compound in accordance with the invention. The capsule filling may be in the form of a powder, or granules, or beads, or may be in the form of a liquid or semi- solid. Where the mixture is in the form of granules, the granules can consist of the extract or compound of the invention alone, or granulated together with a granulating agent, or they can additionally comprise a solid diluent, for example of the type set forth above. CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 16 The granules can be wet granulated or dry granulated as desired. When the capsule filling is in liquid or semi-solid form, the extract or compound can be dissolved or suspended in a semi-solid carrier material such as a polyethylene glycol or a liquid carrier such as a glycol, e.g. propylene glycol, or glycerol. In general, it is preferred that the capsule is in solid or semi- solid form when hard gelatin capsules are used; liquid or semi-solid forms being preferred with soft gelatin capsules. DESCRIPTION OF THE PREFERRED EMBODIMENTS The invention will now be illustrated, but not limited, by reference to the following examples. GENERAL EXPERIMENTAL DETAILS AND ISOLATION PROCEDURE General In the following examples, all melting points are uncorrected. Analytical thin layer chromatography (TLC) was performed on precoated plates (HPTLC plates, silica gel 50 FZSa, Merck) using the following systems: S-1 = CHCI3- MeOH (99:11, S-2 = CHCl3-MeOH (96:4), S-3 - cyclohexane-EtOAc (1:1 ); detection: UV, anisaldehyde reagent (E. Stahl, and U. Kaltenback, Journal of Chromatography, 1961, 5, 351 ]. Unless otherwise stated, the optical properties and UV and IR spectra were recorded as follows: (a]p in CHC13 at 20.degree., CD and UV in MeOH, IR in CHCI3. Unless otherwise stated,'H NMR were run at 360 MHz and "C NMR at 90 MHz in CDCI3 with TMS as internal standard. EIMA were obtained at 70 eV; DCIMS with NH3 or isobutane, respectively. Apart from key ions, the only ions listed are those with relative intensities > 10% and m/z > 100. Column chromatography (CC) and medium pressure liquid chromatography CA 02298677 2000-O1-31 W O. 99/06388 PCT/GB98/02317 17 (MPLC) were carried out on silica gel 60 (Macherey-Nagel) and on LiChroprep~ RP 18 (40-60 ,um, Merck). For CC, Fractogel PVA 500 (Merck), and Fractogel TSK HW-40 (S) (Merck) were also used. High pressure liquid chromatography (HPLC) was performed on LiChrosorb Rp 18 (7 Nm, Merck). Plant material Roots of Aristolochia taliscana Hook (Aristolochiaceae) were collected by Jorge Perez de la Rosa (lnstituto Tecnologico y de Estudios Superiores de Monterrey, ITESM) from Colima (Mexico) and identified by Prof. H. S~nchez. A voucher specimen is held at the Universidad de Guadalajara, Instituto de Botanica, Guadalajara (Mexico). EXAMPLE 1 Extraction and isolation of the Components of Aristolochia taliscana Air dried, pulverized roots and rhizomes (3.5kg) of Aristolochia taliscana were extracted with benzene at room temperature to give 16g of a red-brown extract after removal of solvent. This extract was separated by column chromatography on Fractogel TSK HW 40 (S) with methanol to give 10 fractions (designated A.t.1 to A.t 10), which were then subjected to further chromatographic separation by repeated MPLC or CC using the following systems (a) silica gel, cyclohexane-ethyl acetate gradients, (b) LiChroprep RP 18, MeOH-HZO gradients, (c) Fractogel PVA 500, methanol. The separation scheme followed is set out in Figure 3, and the experimental conditions employed in each of the separation steps are set out in Table 2 below. Purification and final separation was achieved by HPLC on silica gel Nucleosil 50 using cyclohexane-ethyl acetate (8:2) and high pressure liquid chromatography on silica gel RP 18 (LiChrosorb) using methanol-water mixtures, respectively. These procedures afforded the individual compounds 1 to 32 and 34 to 41 besides the mixtures 33, 42 and 43, whose identification was achieved by methylation or methanolysis and subsequent gas chromatographic analysis. CA 02298677 2000-O1-31 W 0.99/06388 PCT/GB98/02317 18 Table 2 Step Applied AdsorbentEluent Column Fractions obtained to No. Fraction dimensions 1 A.t.1 Silica Gradient D 1.2 cm 1 246 mg = 43 gel 361 mg 40 g CH/EA L 46 cm 2 63 mg o 10/0 3 39 mg o 0/10 2 A.t.2 Silica Gradient D 1.2 cm 1 180 mg = 33 gel 431 mg 40 g CH/EA L 46 cm 2 232 mg o 1 0/0 3 15 mg o 0/10 3 A.t.3 Silica Gradient D 2.5 cm 1 209 mg o gel 904 mg 160 g L 46 cm 2 611 mg = A.t. 3.2 4 A.t.3.2 Silica CH1EA D 2.5 cm 1 150 mg o gel 611 mg 160 g 7/3 L 4fi cm 2 431 mg = A.t. 3.2.2 A.t. 3.2.2NucleosilM/EtOH D 2 cm 1 55 mg = 32 60 mg RP-18, 9/1 L 25 cm 2 4 mg o 7pm 6 A.t.4 Silica Gradient D 5 cm 1 39 mg o gel 1079 mg 640 mg CH/EA L 46 cm 2 10 mg o 10/0 3 156 mg = A.t. 4.3 4 308 mg = A.t. 4.4 0/10 5 322 mg = A.t. 4.5 6 51 mg = A.t. 4.6 7 A.T. 43 NucleosiiM/W D 2 cm 1 45 mg o 156 mg RP-18, 96/4 L 25 cm 2 63 mg o 7pm 3 28 mg = 38 8 A.t. 4.4 LiChroprepGradient 0 1.2 cm 1 235 mg = A.t. 4.4.1 308 mg RP-18, MIW L 46 cm 2 31 mg o 40 g 8/2 3 9 mg o 4 l7mgo 1 O/0 9 A.t. 4.4.1NucleosiiM/W D 2 cm 1 90 mg o 120 mg RP-18, 84/16 L 25 cm 2 28 mg = 40 7pm A.t. 4.5 Silica Hrso-PrOHD 2 cm 1 15 mg o Gel Si 30 mg 60, 98/2 L 25 cm 2 11 mg = 39 1 Opm 11 A.t. 4.6 LiChroprepM/W D 1.2 cm 1 23 mg = A.t. 4.6.1 51 mg RP-18, 8/2 L 46 cm 2 20 mg o 40g 12 A.t. 4.6.1NucleosilMIW D 2 cm 1 9 mg = 37 23 mg RP-18, 9/1 L 25 cm 2 5 mg o 7pm 13 A.t. 4.6.2NucleosilM/W D 2 cm 1 1 mg o 20 mg RP-18, 98/2 L 25 cm 2 1 mg o 7pm 3 13 mg = 36 4 4 mg = 35 CA 02298677 2000-O1-31 W O 19/06388 PCT/GB98/02317 19 Step Applied AdsorbentEluent Column Fractions obtained to No. Fraction dimensions 14 A.T. 5 Silica GradientD 2.5 cm 1 115 mg = A.t. gel 5.1 784 mg 160 g CH/EA L 46 cm 2 121 mg o g/2 3 60 mg = A.t. 5.3 4 201 mg = A.t. 5.4 0/10 5 145 mg o 6 54 mg = A.t. 5.6 15 A.t. 5.1 PVA-500 MeOH D 1 cm 1 72 mg o 1 15 mg 30 g L 100 cm 2 8 mg o 3 38 mg = A.t. 5.1.3 16 A.t. 5.1.3PVA-500 MeOH D 1 cm 1 5 mg o 38 mg 15 g L 46 cm 2 30 mg = A.t. 5.1.3.2 17 A.t. 5.1.3.2NucleosilM/W D 0.8 cm 1 21 mg o 30 mg RP-18, 95/5 L 25 cm 2 4 mg = 28 7pm 18 A.t. 5.3 PVA-500 MeOH D 1 cm 1 20 mg = A.t. 5.3.1 60 mg 15 g L 46 cm 2 35 mg o 19 A.t. 5.3.1PVA-500 MaOH D 1 cm 1 17 mg = 21 20 mg 15 g L 46 cm 2 1 mg ~ 20 A.t. 5.4 PVA-500 MeOH D 2.5 cm 1 53 mg = 42 201 mg 100 g L 100 cm 2 120 mg o 21 A.t. 5.6 LiChroprepM/W D 1 .2 1 18 mg = 34 cm 54 mg RP-18, 1 /1 L 46 cm 2 31 mg o 40 g 22 A.t. 6 Silica GradientD 2.5 cm 1 3 mg ~ gel 1750 mg 160 g CHIEA L 46 cm 2 1549 mg = A.t. 6.2 8/2 3 79 mg = A.t. 6.3 4 115 mg = A.t. 6.4 515 23 A.t. 6.2 LiChroprepMIW D 2.5 cm 1 3 mg = A.t. 6.2.1 1549 mg RP-18, 7/3 L 46 cm 2 1540 mg = 16 160 9 24 A.t. 6.2.NucleosilMIW D 2 cm 1 < 1 mg o i 3 mg RP-18, 75/25 L 25 cm 2 2 mg = 6 7~m 25 A.t. 6.3 Silica CHCI3 D 1 cm 1 30 mg = A.t. gel 6.3.1 79 mg 9 g L 20 cm 2 29 mg = A.t. 6.3.2 3 11 mg = A.t. 6.3.3 26 A.t. 6.3.1LiChroprepM!W D 1.2 cm 1 4 mg = 20 30 mg RP-18, 6/4 L 46 cm 2 21 mg o 40 g 27 A.t. 6.3.2LiChroprepM/W D 1.2 cm 1 27 mg = 31 29 mg RP-18, 55/45 L 48 cm 2 2 mg = 30 40 g 28 A.t. 6.3.3PVA 500 MeOH D 1 cm 1 < 1 mg o 1 1 mg 15 g L 40 cm 2 10 mg = 29 29 A.t. 6.4 Silica CHCI3 D 1.2 cm 1 11 mg o gel i 15 mg 40 g L 46 cm 2 16 mg = A.t. 6.4.2 3 73 mg = A.t. 6.4.3 4 5 mg = A.t. 8.4.4 CA 02298677 2000-O1-31 WO-99106388 PCT/GB98/02317 Step Appiied AdsorbentEiuent Column Fractions obtained to No. Fraction dimensions A.t. 6.4.2NucleosilMIW D 2 cm 1 7 mg = 19 16 mg 40 g 6/4 L 25 cm 2 6 mg o 31 A.t. 7 Silica CH/EA D 5 cm 1 1290 mg = 17 gel 6177 mg 640 g 6/4 L 46 cm 2 4350 mg = 7 3 40 mg = A.t. 7.3 3/7 4 91 mg = A.t. 7.4 5 52 mg = A.t. 7.5 6 11 mg = A.t. 7.6 7 328 mg = A.t. 7.7 32 A.t. 7.3 LiChroprepM/W D 1.2 cm 1 24 mg = A.t. 7.3.1 40 mg RP-18, 5/5 L 46 cm 2 7 mg o 40 g 9/1 33 A.t. 7.3.1LiChroprepM/W D 1.2 cm 1 13 mg o 24 mg RP-18, 3I7 L 46 cm 2 10 mg = A.t. 40 g 7.3.1.2 34 A.t. 7.3.1.2NucleosilM/W D 2 cm 1 2 mg o 10 mg RP-18, 75.25 L 25 cm 2 3 mg o 7pm 3 2mg = 12 A.t. 7.4 LiChroprepGradient D 1.2 cm 1 42 mg = A.T. 7.4.1 91 mg RP-18, MlW L 46 cm 2 5 mg o 40 g 5/5 3 17 mg = A.t. 7.4.3 4 4 mg = 26 9l1 36 A.t. 7.4.1NucleosilM/W D 2 cm 1 3 mg o 42 mg RP-18, 7/3 L 25 cm 2 7 mg = 9 7pm 3 13 mg = 10 4 < 1 mg o 5 2mg = 18 37 A.t. 7.4.3TSK HW MeOH D 1 cm 1 1 1 mg = A.t. 7.4.3.1 13 mg 50s L 100 cm 2 1 mg o ca. 100 ml 38 A.t. 7.4.3.1LiChrosorbCHIEA D 2 cm 1 6 mg = 22 11 mg Si 60, 8/2 L 25 cm 2 3 mg = 23 lacetylatedl1 Opm 39 A.t. 7.5 LiChroprepGradient D 1.2 cm 1 30 mg = 4 52 mg RP-18, M/W L 46 cm 2 9 mg o 40 g 5/5 9/1 A.t. 7.6 LiChroprepM/W D 1.2 cm 1 4 mg = 13 11 mg RP-18, 5/5 L 46 cm 2 6 mg o 40 g 41 A.t. 7.7 LiChroprepGradient D 1.2 cm 1 4 mg = 15 328 mg RP-18, M/W L 46 cm 2 189 mg o 40 mg 1 /1 3 103 mg o 10/0 CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 21 Step Applied AdsorbentEluent Column Fractions obtained to No. Fraction dimensions 42 A.t. 8 Silica Gradient D 1.2 cm 1 384 mg = 8 gel 771 mg 40 g CH/EA L 46 cm 2 165 mg = A.t. 8.2 8l2 3 44 mg = A.t. 8.3 4 93 mg = A.t. 8.4 5/5 5 34 mg = A.t. 8.5 6 8 mg = A.t. 8.6 0/10 43 A.t. 8.2 LiChroprepMJW D 1.2 cm 1 80 mg = A.t. 8.2.1 165 mg RP-18, 75/25 L 46 cm 2 74 mg 40 g 44 A.t. 8.2.1Silica C/M D 1.2 cm 1 15 mg = A.T. gel 8.2.1.1 80 mg 40 g 99/1 L 46 cm 2 20 mg = A.t. 8.2.1.2 3 36 mg 45 A.t. 8.2.1.1PVA 500 M/C D 1 cm 1 9 mg = 14 15 rng 15 g 911 L 45 cm 2 4 mg 46 A.t. 8.2.1.2PreparativeC/M Laufstrecke1 8 mg = 11 20 mg Silica 99.5/0.5 10 cm 2 11 mg gel- DC 47 A.t. 8.3 NucleosilM/W D 2 cm 1 7 mg = A.t. 8.3.1 44 mg RP-18, 83/17 L 25 cm 2 8 mg = 5 7pm 3 19 mg 48 A.t. 8.5 NucleosilM/W D 2 cm 1 26 mg = 3 34 mg RP-18, 911 L 25 cm 2 3 mg = 24 7pm 49 A.t. 8.6 PVA 500 MeOH D 1 cm 1 3 mg - 2 8 mg 15g L 45 cm 2 4 mg 50 A.t. 9 Silica Gradient D 2.5 cm 1 56 mg = A.t. gel 9.1 229 mg 80 g CHIEA L 2~ cm 2 20 mg - A.t. 92. 8/2 3 136 mg 5/5 0/10 51 A.t. 9.1 NucleosilM/W D 2 cm 1 9 mg = 25 56 mg RP-18, 96.4 L 25 cm 2 33 mg 7pm 52 A.t. 9.2 NucleosilM/W D 2 cm 1 4 mg = 1 20 mg RP-18. 9/1 L 25 cm 2 13 mg 7pm 53 A.t. 10 Silica C/M D 1.2 cm 1 23 mg = A.t. gel 10.1 266 mg 40 g 10/0 L 48 cm 2 141 mg 3 83 mg 95/5 54 A.t. 10.1Silica TIEA D 1 cm 1 18 mg gel 23 mg 9 g 6/4 L 18 cm 2 4 mg = 27 Abbreviations: D: diameter, L: length, C: chloroform, CH: cyclohexane, EA: ethyl acetate, H: hexane, M: methanol, T: toluene, W: water CA 02298677 2000-O1-31 WO-99/06388 PCT/GB98/02317 22 The compounds isolated from the benzene extract are listed below in Table 3. Those compounds already known as natural products are referred to in Table 3 by their chemical names, whilst those compounds not previously recognised as natural products are identified by code number. The full chemical names and spectroscopic and other characterising data for the new natural products are given in the paragraphs following Table 3. Table 3 Compounds isolated from the Benzene Extract of the Root of Aristolochia taliscana Compound Type Compound (Compound No.l Content 1%)~ Alkaloid Aristolactam I (1 ) ~ 0.03 Aristolactam A II1 (2) 0.02 Aristolactam B III (3) 0.2 Aristoiactam C III (4) 0.2 Taliscanine (5) 0.06 Lignans Machilin-F (6) 0.02 Neolignans Benzofuran-type Eupomatenoid-7 (7) 34 Eupomatenoid-1 (81 3 Compound 9 0.05 Compound 10 0.1 Compound 11 0.06 Compound 12 0.02 Compound 13 0.03 Compound 14 0.07 Compound 15 0.03 Dihydro-benzofuran( 1-Licarin A 116) ~ 2 type (-)(2S,3S1-Eupomatenoid-8 (17) 10 1-112S,3S)-Machilin-B (18) 0.02 Compound 19 0.05 (-112S,3S)-5-Methoxylicarin-A 0.03 (20) CA 02298677 2000-O1-31 W d 99/06388 PCT/G898/02317 23 Compound Type Compound (Compound No.) Content (%1'" (+)12R,3R)-Dihydrocarinatidine0.1 (21) Oligomers Compound 22 0.05 Compound 23 0.02 Compound 24 0.02 Compound 25 0.07 Compound 26 0.03 Hybrids Compound 27 0.03 Compound 28 0.03 Phenylpropanes Coniferyl alcohol (29) 0.08 Ferulaaldehyde (30) 0.02 Vanillin (31 ) 0.2 Sterols Beta-sitosterol (32) 0.4 Mixture of 3-0-acyl-beta-sitosterols1.4 (33) Terpenoids Compound 34 0.1 Sandaracopimaradiene (35) 0.03 Beta-caryophyllene (36) 0.1 Caryophyllene oxide (37) 0.07 ent-Germacrene-D (38) 0.2 ent-Germacra-4(15), 5, 10 (14)-trien-1-beta-0.09 of (39 Spathulenol (40) 0.2 Others D-fructose (41 ) 1.3 Mixture of fatty acids (42) 0.4 Mixture of triglycerides (43) 1.9 No aristolochic acids were detected in the extract. CA 02298677 2000-O1-31 W O~ 99/06388 PCT/GB98/02317 24 The aristolactams referred to in the table have the following structural formulae: Ra Re Rn R~ Rc Re I I Aristolactam I H 0-CHZ-O H OCH3 Aristolactam A H OH OCH3 OCH3 H III Aristolactam B H OCH3 OCH3 OCH3 H III Aristolactam C CHZOH OCH3 OCH3 OCH3 H III Taliscanine H OCH3 OCH3 OCH3 H Phvsico-chemical and Spectroscopic Properties of the Novel Natural Products ( t )-5-( 1 -Hydroxyallyll-2-(4-hydroxy-3-methoxvphenyl)-7-methoxy-3- methvlbenzofuran (Compound 9). Crystals (5 mg). Mp 164-167.degree. (from MeOH). TLC: Rf 0.42(S-1 ); anisaldehyde: violet. [ado~0.degree. (c.0.1). IRvmeX cm-' :3540(OH), 3020, 1515. UV~tmax nm(loge):221 (3.42), 305(3.381; + Na0H:21213.82), 328(3,46). 'H NMR(250 MHz):62.00(lH,d,J=3.5Hz,OH-8), 2.41(3H,s,Me- 3),3.99(3H,s,OMe1,4.03(3H,s,OMe),5.23(1 H,dt,J, = 10.5,Jz= 1.5Hz,H- 1081,5.31 (1 H,m,H-8),5.41 (1 H,dt,J, = 17,Jz= 1 .SHz,H-10A),5.75(1 H,s,OH- 14),6.14( 1 H,ddd,J, = 17,J2 = 10.5,J3 = 6Hz,H-91,6.8311 H,d,J = 1 .SHz,H- 6),7.00(1 H,d,J =BHz,H-1 5),7.1 2(1 H,d,J = 1 .5Hz, H-4, 7.29 (1H,dd,J,=8,Jz=2Hz,H-16), 7.33(lH,d,J=2Hz,H-12). "C NMR (60MHz):a9.6(Me-3),56.5(2xOMe),76.5(C-8),106.6 (C-61,110.0(C- CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 1 2),1 1 0.9(C-3),1 1 1 .3(C-4), 1 1 4.6(C-1 51, 1 1 6.5(C-1 01, 1 21 .21C- 161,124.5(C 1 1 ),134.1 (C3a),140.1 (C-5),142.6(C-91.143.31C-7a),146.2(C- 7),148.11C-14),149.2(C-13),152.9(C-2). EIMS mlz (rel. int.): 340[M]+(100),323(14),297(11 ),295(1 1 ),284(12). 2-(4-Hvdroxv-3-methoxvphenvl)-3-hvdroxvmethvl-7-methoxv-5-(E)- propenvlbenzofuran (Compound 101 Crystals (12mgl. Mp 175-179.degree. (from MeOH). TLC:Rf0.3(S-1 ); anisaldehyde:grey. IRvmax om':353910H), 1600, 1515, 1466. UVamex nm(iogs):231 (3.38), 266 (3.44),304 (3.341; + NaOH:240 (3.41 ), 29513.25), 328(3.3). 'H NMR (250 MHz): d1 .57(1 H,t,J =4Hz, OH-3), 1 .90(3H,dd,J, =6.5Jz= 1 .SHz, Me-10), 3.95(3H,s,OMe), _4.04(3H,s,OMel, 4.91 (2H,d,J = 4Hz, CH20H), 5.8 i ( 1 H,s,OH- 14), 6.23(1 H,dq,J, = 16,J2=6.5Hz,H-9), 6.48(1 H,dq,J, = 7 6,Jz1 .SHz,H-8), 6.83(1 H,d,J=1.SHz,H-6), 7.0111 H,d,J=8Hz,H-15), 7.18(1 H,d,J= 1.5Hz,H-4), 7.38( 1 H,dd,J, = 8,Jz = 2Hz,H-16), 7.41 ( 1 H,d,J = 2Hz,H-12). "C NMR:d'18.4(Me- 10), 55.7(CHZOH1, 56.1 (2xOMe), 104.8(C-6), 109.0(C-41, 110.0(C-12), 113.8(C- 3), 1 14.7(C-15), 121.3(C-16), 122.4(C-1 1 ), 124.81C-91, 131.2(C-3a), 131.3(C- 8), 123.3(C-5),142.3(C-7a1,145.OIC-7),146.6(C-14),146.7(C-13),154.6(C-2). EIMS m/zlrel.int):340[M]"'(1001, 323(15),291 (19),151 (10). 2-(4-Hydroxy-3-methoxyahenyl)-7-methoxy-3-methyl-5-1(E)-3- oxopropenyllbenzofuran (Compound 11) Crystals (8 mg). Mp 169-170.degree. (from MeOH). TLC:R,0.39(S-1 ); anisaldehyde:blue. IR vmex cm~':353810H), 16721C01, 1610, 1514. UV ~Imex nm(IogE):213(4.04), 291 (4.91 ), 314(4.31 ); +NaOH:21 5(4.93), 33714.36). 'H NMR(250MHz):d2.4613H,s,Me-3), 3.99(3H,s,OMe), 4.08(3H,s,OMe), 6.73(1 H,dd,J, =16,J2=8Hz,H-81, 7.00(1 H,d,J = 2Hz,H-61, 7.04(1 H,d,J = 2Hz,H- 15), 7.3011 H,d,J = 8Hz,H-16), 7.32( 1 H,dd,J, = 8,Jz = 2Hz,H-12), 7.33(1 H,d,J = 2Hz,H-4), 7.58( 1 H,d,J =16Hz,H-8), 9.72( 1 H,d,J = 8Hz,CHO). ' 3C NMR(60MHz):d9.51Me- 3), 56.1 (2xOMe), 105.7(C-6), 109.61C-12), 110.1 (C-3), 113.8(C-4), 114.7(C-15), 120.8(C-16), 122.9(C-11 ), 124.5(C-9), 129.7(C-5), 133.5(C-3a), 144.7(C-7a), 145.4(C-7), 146.3(C-14), 146.8(C-13), 152.6(C-2), 153.91C-8), 193.6(C-10). EIMS mlz (rel. int.):338[M]+(96), 31 1 (19), 310(100), 295(28), 267(291, 178(101, 169112), 165(12), 152(11). CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 26 Formvl 3 14 hvdroxv-3-methoxyahenyl)-7-methoxv-3-methvlbenzofuran LCompound 121 Crystals (2 mg). Mp 162-165.degree. (from MeOH). TLC:R,0.43(S-1 ); anisaldehyde:light blue. IRvmex cm~':3540(OH), 3023, 1688(CO), 1515. UV~Im~ nm(loge):231 (4.40), 283(4.61 ), 307(sh,4.53); + NaOH:240(4.44), 329(4.62).'H NMR:d2.48(3H,s,Me- 3); 4.00(3H,s,OMe), 4.07(3H,s,OMe), 5.80(1H,s,OHI, 7.03(1H,d,J=8Hz,H-151, 7.32(1 H,dd,J, =8, JZ=2Hz,H-16), 7.33(1 H,d,J =2Hz,H-12), 7.37(1 H,d,J =1.SHz,H- 4), -7.68(1 H,d,J =1.SHz,H-6), 10.011 H,s,CHO). "C NMR: d9.5(Me-31, 56.1 (2xOMe), 104.71C-6), 1 10.5(C-31, 1 14.6(C-4), 1 17.4(C-15), 120.8(C-16), 122.81C-1 1 ), 132.9(C-3a), 133.1 (C-5), 145.8(C-7), 146.2(C-14), 146.4(C-13), 146.8(C-7a), 153.0(C-21, 192.0(CO). E1MS m/z (rel. int.):312(M]+(100), 297114), 269(12), 156115). 2-(4-Hvdroxv-3-methoxvohenvll-5-((E)-3-hvdroxvprooenvll-7-methoxv-3- methylbenzofuran (Compound 13) Crystals (7 mg). Mp 180-183.degree. (from MeOH). TLC:R,0.16(S-1 ); anisaldehyde:violet. IRvmex cm':35401OH), 3020, 1612, 1515. UV Amax nm(loge):232(3.16), 271 (3.30), 306(sh 3.23); +Na0H:240(3.29), 291 (3,191, 329(3.33). 'H NMR x1.45(1 H,t,J = 5.5Hz, OH-10), 2.41 (3H,s,Me-3), 3.99(3H,s,OMe), _4.05(3H,s,OMe), 4.35(2H,dd,J, = 5.5,J2=1 Hz,CH20H), 5.75(1H,s,OH-14), 6.37(1H dt,J,=l6,Jz=5.5Hz,H-9), 6.71 (1 H,dt,J, =16,J2=1 Hz,H-8), 6.88(1 H,d,J = 1.SHz,H-6), 7.0011 H,d,J =8.5Hz,H- 15), 7.11(1H,d,J=l.5Hz,H-4), 7.29(1H,dd,J,=8.5,J2=2Hz,H-16), 7.32(1 H,d,J = 2Hz,H-12). "C NMR:d9.6(Me-3), 56.1 (2xOMe), 63.8(C-101, 104.8(C-6),109.5(C-4),110.21C-3 and C-12),114.4(C-15),120.7(C-16),123.5(C- 1 1 ), 127.2(C-9), 132.1 (C-8), 132.3(C-3a), 133.21C-5), 142.6(C-7x1, 145.0(C- 7), 145.8(C-141, 146.6(C-13), 151.8(C-2). EIMS m/z (rel. int.): 340(MI'(100), 312(12), 311 (20), 297122), 284(37), 282(15), 281 (121, 279(11 ), 165(13), 151 (14), 149(101, 55(10). 2-(3 4-Dihydroxvohenyl)-7-methoxy-3-methvi-5-(E)-propenylbenzofuran (Compound Oil (9 mg). TLC:R,0.15(S-2); anisaldehyde:grey. IR vmex cm ':3548(OH), 3015, 1600, 1523, 1483. UV ~mex nm(loge):231 (4.49), 264(4.59), 207(sh.4.46); *rB CA 02298677 2000-O1-31 WO~ 99/06388 PCT/GB98/02317 27 +NaOH:242(4.60), 327(4.44). 'H NMR(CD30D, 250 MHzl:d1.8813H,dd,J, =6.5,JZ=1.SHz,Me-10),2.37(3H,s,Me-3), 4.01 (3H,s,OMel, 6.22(1 H,dq,J, = 1 6,J2=6.5Hz,H-9), 6.47(1 H,dq,J, = 16,Jz= 1 .SHz,H-8), 6.85(1 H,d,J = 1.SHz,H-6), 6.88(1 H,d,J =8.5Hz,H-15), 7.01 (1 H,d,J =1.SHz,H- 4), 7.14( 1 H,dd,J, = 8.5Hz,J, = 2Hz,H-16), 7.26(1 H,d,J = 2Hz,H-1 2). "C NMR(CD30D,60MHz):d9.61Me-3),18.6(Me-10), 56.7(OMe), 105.8(C-6), 110.1 (C- 4), 110.5(C-3),1 14.9(C-12),116.6(C-15), 119.9/C-16), 124.51C-11 ), 124.81C- 9), 132.9(C-81, 1.34.4(C-3a1, 135.1 (C-5), 143.3(C-71 ), 146.2(C-7), 146.5(C-14), 146.9(C-13), 152.91C-2). EIMS m/z (rel. int.):310[Ml+1100), 309(10). ervthro 5 !1 2 Dihvdroxvproavl) 2 (4-hvdroxv-3-methoxyphenvll-7-methoxv-3- _methvibenzofuran (Compound 151 Amorphous (3 mg). TLC:R,0.16(S-2);anisaldehyde:violet. [a)o+ 17.degree.(c0.2). IR v,",x cm ':3435(OH), 2927, 1655, 1516, 1462. UV ~imax nm(loge):216(4.16), 304(4.04):+Na0H:211 (4.80),328(4.11).'HNMR:d1.11(3H,d,J=6.5Hz,Me-101, 2.42(3H,s,Me- _ -3), 2.44(lH,br d,J=3Hz, OH-9), 2.6111H,br d,J=3HZ,OH-8), 3.90(1 H,m,H-9), 3.9913H,s,OMe), 4.0513H,s,OMe), 4.48(1 H,dd,J, =7.5,J2=3Hz,H- 8), _5,7511 H,s,OH-14), 6.80(1 H,d,J=1.5Hz,H-6), 7.01 (1 H,d,J=8Hz,H-15), 7.10( 1 H,d,J =1.5 Hz, H-4),7.30( 1 H,dd,J, = B,Jz = 2Hz,H-16),7.33( 1 H,d,J = 2Hz,H- 12). '3C NMR160MHz):d9.61Me-3), 16.91Me-10), 56.1, 56.212xOCH3), 72.5(C-9), 80.1 (C-8), 105.31C-6), 109.5(C-12), 109:9(C-4), 1 10.1 (C-3), 1 14.5(C-15), 120.7(C-16), 123.5(C-11 ), 133.0(C-3a), 136.4(C-5), 142.5(C-7a), 145.0(C-7), 145.9(C-14),146.6(C-13),152.6(C-2). EIMS mlz(rel.int.):358[M1 ''1100), 328(16), 314(21), 313(81), 285(52), 258(11), 257(57), 253(28), 225(14), 133(13). (2R 3R1 2 3 Dihvdro 2 14 hvdroxv-3-methoxvphenvll-3-hvdroxvmethvl-7-methox~- (E)-nroaenvlbenzofuran (Compound 19) Amorphous (6 mg). TLC:R,0.3(S-1 ); anisaldehyde:red. [a)p+65.degree.(c.0.2). CDamex nm~e):235(-3.15), 2601+3.14), 285(+2.39). IRvmex cm ':3543(OH),3019,1613,1518,1499,1466. UV~i,"ax nm(loge1:204(4.59),218(4.49),273(4.23); +NaOH:211 (4.93), 268(4.381. 'H NMR(CD30D):d1.78(3H,dd,J,=6,J2=2Hz,Me10), 3.47(lH,m,H-3), 3,78(2H,d,J=7Hz,CH OH), 3.80(3H,s,OMe), 3.86(3H,s,OMe), 5.50(lH,d,J-6Hz,H- 2), 6.1 1 (1 H,dq,J, =16,J2=6.5Hz,H-9), 6.33(1 H,dq,J, =16,J2=2Hz,H-8), 6.76(lH,d,J=8Hz,H-15), 6.82(lH,dd,J,=8,Jz=2Hz,H-161, 6.86(lH,br s,H-4), CA 02298677 2000-O1-31 WO-99/06388 PCT/GB98/02317 28 6.88(1 H,br s,H-61, 6.9411 H,d,J = 2Hz,H-12). "C NMR(60MHz):18.3(Me-10), 53.7(C-31, 56.0(2xOMe), 64.0(CH20H-3), 88.7(C-2), 108.8(C-121, 110.0(C-6), 1 13.91C-4), 1 14.3(C-15), 1 19.4(C-161, 123.8(C-9), 127.91C-11 ), 129.7(C-81, 132.3(C-5), 133.0(C-3a1, 144.4(C-7), 145.7(C-14), 146.71C-7a), 147.6(C-13), EIMS m/z (rel.int.):342[M]+(52), 324(78), 310(20), 309(100), 293128), 292(32), 2211101, 165(14), 152(13), 151 (22), 137(17). erythro-1-(4-Acetoxv-3-methoxyahenvl)-2-f4-(7-methoxv-3-methyl-5-(E)- gropenvlbenzofuran-2-vl)-2-methoxyahenoxvlprooylacetate (Compound 22) Colourless crystals (5 mgl. MP 156-158.degree. (from MeOH). TLC:Rf0.54(S- 3); anisaldehyde:grey. (a]p+18.degree.(c.0.1). IRvmex cm ':3018, 1762,1741,1510. UV ~meX nm(loge):226(4.08), 266(4.10), 308(4.08). 'H NMR:d1.31(3H,d,J=6.5Hz, Me-9'), 1 .89(3H,dd,J,=6.5,J2= 1 .SHz,Me-10), 2.1 1 (3H,s,MeCO-7'), 2.25(3H,s,MeCO-4'), 2.40(3H,s,Me-3),, 3.83(3H,s,OMe), 3.89(3H,s,OMe), 4.01 (3H,s,OMel, 4.77(1 H,m,H-8'), 5.97 (1 H,d,J =4.5Hz,H-7'), 6.24(1 H,dq,J, = 1 6,J2=6Hz,H-9), 6.50(1 H,dq,J, = 1 6,Jz= 1 .SHz,H-81, 6.80(1 H,d,J=1.SHz,H-6), 6.9111 H,d,J=8Hz,H-15), 6.96(1 H,d,J=8.5Hz,H-6'1, 6.97(1H,dd,J,=8.5, Jz=2HzH-5'), 7.01 (1H,br s,H-4), 7.08(1H,d,J=2Hz,H-2'), 7.29(lH,dd,J,=8,JZ=2Hz,H-16),7.32(1H,d,J=2Hz,H-12). "CNMR:d9.6(Me-3), 15.5/Me-9'), 18.4(Me-10), 20.7(MeCO-4'), 21.21MeC0-7'), 56.0,56.113xOMe), 76.6(C-7'),78.0(C-8'1,104.7(C-6),109.2(C-4),110.8(C-3),111.3(C-12),112.1 (C- 2'),1 17.7(C-5'),1 19.6(C-15),119.91C-6'),122.41C-16),124.4(C-9),125.8(C-11 ), 131.5IC-8), 133.0(C-3a), 133.71C-5), 135.9(C-1'), 139.6(C-14'), 142.2(C-7a), 144.9(C- _7), 147.1 (C-14), 150.9(C-13), 151.3(C-3'1, 168.9(MeCO-4'), 169.9(MeCO-7'). EIMS mlz frel.int.):588(M]+(61, 366(14), 325(20), 324(100), 265131 ), 223(54), 181 (27), 164(25). threo- 1 -(4-Acetoxv-3-methoxvphenyl)-2-(4-(7-methoxv-3-methyl-5-IE)- propenylbenzofuran-2~r1)-2-methoxyphenoxylpropyl-acetate (Compound 23) Mp 155-158.degree. (from MeOH). TLC:R,0.54(S-3); anisaidehyde:grey. (a)o + 35 .degree. (c.0.1 ). IRvmax cm ' :3018,1762,1741 ,1510. UV nm(loge1:226(4.08), 266(4.10), 308(4.08).' H NMR: d1.24(3H,d,J = 6.5Hz,Me-9'1. 191(3H,dd,J,=6.5, JZ=2Hz,Me-10), 2.04(3H,s,MeCO-7'1, 2.3013H,s,MeCO-4'), 2.43(3H,s,Me-31, 3.85(3H,s,OMe), 3.9213H,s,OMe), 4.04(3H,s,OMe), CA 02298677 2000-O1-31 W0~99/06388 PCT/GB98/02317 29 4.65 ( 1 H,m,H-8'), 5.99( 1 H,d,J = 6.5Hz,H-7'), 6.22( 1 H,dq,J, =16,J2 = 6.5Hz, H-9), 6.5011 H,dq, J, = 1 6,J2=2Hz,H-8),6.84(1 H,d,J = 1 .5Hz,H-6), 6.99(1 H,dd,J, =8,J2=2Hz, H-16), 7.0211 H,d,J =BHz,H-15), 7.0311 H,d,J =1.5Hz,H- 4), 7.03( 1 H,d,J = 8.5Hz H-1 5'), 7.04( 1 H,d,J = 2Hz,H-1 2), 7.31 ( 1 H,dd,J, = 8.5,J2 = 2Hz,H-16' ), 7.35 ( 1 H,d,J = 2Hz,H-12'), "C NMR:d9.6(Me- 3), 16.7(Me-9'), 20.7(MeCO-4'), 21.1 (MeCO-7'), 56.0,56.1 (3xOMe), 76.6(C-7'), 77.8(C-8'), 104.6(C-6), 109.2(C-4), 110.7(C-3), 111.2(C-12), 111.9(C-2'), 116.8(C-5'), 1 19.8(C-151, 119.9(C-6'), 122.7(C-16), 124.4(C-9), 125.5(C-11 ), 131.5(C-8), 133.0(C-3a), 133.7(C-5), 136.0(C-1'), 139.8(C-4'), 142.2(C-7a), 144.9(C- _71, 147.8(C-14),150.5(C-2), 151.0(C-13), 15 i .2(C-3'),168.8(MeCO- 4'l, 169.9(MeCO-7'). EIMS m/z (rel.int.):588tM]+(6), 366115), 325(20), 324(100), 265(30), 223(54), 181127), 164(25). rhreo-1-I2-(4-Hvdroxy-3-methoxyphenyll-7-methoxv-3-methylbenzofuran-5-yll-2-(4- (3-methyl-5-(e)-propenvlbenzofuran-2-vl)-2-methoxvphenoxv)propan-1-of (Compound 241 Amorphous (3mg). TLC:R,0.69(S-2);anisaldehyde:violet. fa]p+20.degree.(c.0.2). IRvmax cm ':3540(OH),3020,2938,1614,1511,1466. UV.ImaX nmlloge):229(4.16), 266(4.20), 308(4.141; +NaOH: 23914.43), 330(4.46). 'H NMR: d0.98(3H,d,J = 6.5Hz,Me-10'1, 1 .8913H,dd,J, = 6.5, JZ= 1.SHz,Me-10), 2.36(3H,s,Me-3'), 2.43(3H,s,Me-3),3.98,4.01,4.02,4.06 (l2H,s.4xMe), 4.22(1 H,m,H-9'), 4.69(1 H,d,J =8.5Hz,H-8'), 5.74(1 H,s,OH-14'), 6.20(1 H,dq,J, =16,J2=6.5Hz,H-9), 6.48(1 H,dq,J, = 16,Jz= 1.5Hz-H-81, 6.81 (1 H,d,J =8.5Hz,H-15), 6.81 (1 H,d,J =1.5Hz,H-6), 6.89(1 H,d,J =1.5Hz,H- 6'), 7.0011 H,d,J =8Hz,H-15'), 7.01 (1 H,d,J =1.SHz,H-4), 7.0711 H,dd,J,-8.5, JZ=2Hz,H- 16), 7.0911 H,d,J=1.SHz,H-4'), 7.29(1 H,dd, J, =8.5,J2 - 2Hz,H-16'), 7.31 (1 H,d,J = 2Hz,H-12'), 7.35( 1 H,d,J = 2Hz,H-12). "CNMR:d9.6(Me-3), 9.7(Me- 3'), 18.0(Me-10'), 18.4(Me-10), 56.0, 56.1,56.3(4xOMe), 71.81c-9'), 91.3(C- 8'), 104.7(C-6), 105.4(C-6'), 109.2(C-4), 109.6(C-12'), 110.2(C-121, 110.4(c-4'), 1 10.6(C-3), 110.9(C-3'), 114.5(C-15), 118.5(C-15'), 119.8(C-16), 120.8(C- 16'), 123.2(C-1 1'), 124.5(C-91, 126.2(C-1 11, 131.4(C-8), 132.91C-31'), 133.1 (C- 3a), 133.7(C-5), 133.91C-5'), 142.2(C-7a1, 142.6(C-7a'), 144.91C-7), 145.2(C-7'), 145.9(C-14'), 146.6(C-13'), 147.9(C-4), 150.7(C-13), 151.1 (C-2'), 151.9(C-2). DCIMS m/z (rel.int.):665fm+h]110), 381(9), 367(12), 343(12), 342(25), CA 02298677 2000-O1-31 WO-99/06388 PCT/GB98/02317 3411100), 340(24), 326(22), 325194), 324144). 2 Methoxv 4 I7 methoxv 3 methyl 5 (E)-proaenylbenzofuran-2-vll-6-(4-(7-methoxv 3 methyl 5 (E) prooenvlbenzofuran 2 vll 2 methoxvphenoxvlahenol (Compound 2~ Amorphous (9 mg). TLC:R,0.83(S-1 ); anisaldehyde:grey. IRv",e,~ cm ':3538(OH), 3 0 2 0 , 2 9 3 9 , 1 6 1 3 , 1 5 9 9 , 1 5 1 0 . U V il ,nax nm(loge):233(4.141,26714.48),309(4.46); + NaOH:21515.231, 316(4.41 ). 'H NMR(250 MHz):a1.91 (6H,m,Me-10 and Me10'), 2.31 (3H,s,Me-3'), 2.42(3H,s,Me 3),3.99,4.01,4.04112H,s,4xOMe), 6.20(2H,m,H-9 and H 9'),6.47(1 H,dq,J, =16,J2= 1.SHz,H-8'), 6.50(1 H,dq,J, =16,2= 1.SHz,H 8),6.81 l1 H,d,J =1.SHz,H6'1,6.84( 1 H,d, J =1.SHz,H-6),7.00(1 H,d,J =1.SHz,H 4'),7.03(1 H,d,J =1.SHz,H4),7.04 (1 H,d,J = 2Hz,H-12'),7.05(1 H,d,J =SHz,H 15),7.18(1H,d,J=2Hz,H16'), 7.31 (1H,dd,J,=8,J2=2Hz,H 16),7.45(1H,d,J=2Hz,H12). "C NMR(60MHz): d9.5,9.6(Me-3,Me-3'), 18.41Me 10,Me-10'1, 56.1,56.3,56.5(4xOMel, 104.7,104.810-6,C-6'1, 106.1 (C-16'), 109.3,109.810-4,C-4'), 111.210-3'), 111.3(0-121, 111.5(0-3), 111.9(0-12'), 116.8(0-15), 119.9(0-161, 122.8(0-11), 124.4,124.5(0-9,C-9'), 127.6(0-11'), 132.7,132.9(0-8,C-8'), 133.7,133.8(0-3a,C-3a'), 137.3(0-14'), 142,1,142.3(C 71,C-7a'), 143.810-14), 144.8,144.9(0-7,C-7'), 145.8(c-15'), 148.2(0-13,C 13'i,150.4, 150.910-2,C-2'). DCIMS m/z (rel.int.):647IM+H)+(100), 646(44), 473(18), 369(12), 341(26), 339(16), 326111), 325(46), 324(23), 309(34), 308(13), 283(20), 1131191, 107(18), 105(12). 8 2' 9 3' Tetrahydro-bis-euoomatenoid-7 (Compound 26) Crystals (4 mg). Mp 175-179.degree. (from MeOH). TLC:R,0.26(S-1 ); anisaldehyde:grey- blue. IalotO.degree.Ic.0.1). IRvmexcm ':3540(OH), 3020,1618,1465. UVamexnm(loge) 217(5.031, 279(4.83), 2971sh 4.79), +NaOH: 261 (4.76), 30514.75), 327fsh 4,7g), 'H NMRd1.05(3H,s,Me-3'), 1.31(3H,d,J=6.5Hz,Me-101, 1 .8613H,dd,J, =6.5,J2= 1 .SHz,Me-10'), 2.37(3H,s,Me-3),2.9711 H,dq, J, = 1 1 ,JZ= 6.5Hz,H-9), 3.50(3H,z,OMe-13'), 3.76( 1 H,d,J = 1 1 Hz,H-8), 3.80(3H,s,OMe-7), 3.9213H,s,OMe-13'), 4.0013H,s,OMe-7'), 6.17(1 H,dq, J, =16,J2=6.5Hz,H-9'1, 6.42(1 H,dq,J, = 16,J2=1.SHz,H-8'), 6.48(1 H,s,H-6), 6.63(1H,d,J=8.5Hz,H-15'), 6.75(1H,d,J=2Hz,H-12'), 6.83(lH,dd, J,=8.5, J2 = 2Hz, H-16'),6.85( 1 H,d,J =1.5Hz,H-4'), 6.90( 1 H,d,J = 8Hz,H-15),6.9411 H,s,H- CA 02298677 2000-O1-31 W0~99/06388 PCTlGB98/02317 31 4), 6.98(1 H,d,J = 1 .5Hz,H-6'), 7.2211 H,dd,J, =B,Jz= 2Hz,H-16), 7.33( 1 H,d,J = 2Hz,H-12). "C NMR:a9.6 (Me-3), 16.2(Me-10), 18.51Me-10'), 22.1 (Me-3'), 42.7(C-9), 56.2(C-3'), 56.5,56.7,57.3,58.214xOMe), 98.1 (C-8), 107.9(G2'), 109.7(C-6), 110.6(C-4), 110.91C-6'), 111.3(C-12), 111.8(C-4'), 1 15.5(C-15'),116.5(C-15),1 17.4(C-12'),120.7(C-16'),121.21C-16),124.1 (C-9'), 124.5~C-11 ), 128.8(C-11'), 132.4(C-8'), 133.7(C-5'), 134.0(C-3a), 135.3(C-51, 136.0(C-3a'), 142.5IC-7a), 146.0(C-7), 146.4(C-7'), 146.9(C-13'), 147.7(C- 7a'), 148.0(C-14'), 149.2(C-14), 152.6(C-21. CIMS m/z (rel.int.):649[M+H]+ (13), 648(7), 367(121, 326125), 325(1001, 324(881. 15 (Aristolactam I 9 yl1 eu omatenoid-7 IComaound 27) Yellow crystals (4 mg). Mp 165-170.degree. (from MeOH). TLC:R,0.4315-2); anisaldehyde:green. IRvm~cm ':3531,3442,3020,3011,1699,1610,1482,1466. UV ~lmeX nm(IogE):256 (4.83), 267(sh 4.79), 30114.73), 405(4.00). 'H NMR IC5p5N):b1.86 (3H,dd,J,=6.5,Jz=l.5Hz,Me-10), 2.44(3H,s,Me-3), 3.52f3H,s,OMe-8'), 3.8013H,s,OMe-13), 3.96(3H,s,OMe-7), 6.30(1 H,dq,J; = 1 6,Jz=6.5Hz,H-9), 6.34(2H,d,J = 1 Hz,OCHzO), 6.63(1 H,dq,J, = 1 6,Jz= 1 .5Hz,H-8), 7.09(1 H,d,J = 1 .5Hz,H-6), 7.13( 1 H,dd,J, = 8,Jz=1 Hz,H-7'), 7.27(1 H,d, J =1.SHz,H-4), 7.57(1 H,d,J = 2Hz,H- 12), 7.5811 H,t,J =BHz,H-6'), 7.81 (1 H,d,J =2Hz,H-16), 7.84(1 H,s,H-2'), 8.57(1 H,dd,J; = B,Jz=1 Hz,H-5'), 1 1.26( 1 H, br s,OH), 12.02(1 H,br s, NH). "C NMR(C5D5N):b9.8(Me-3), 18.5(C-10), 55.9,56.4,56.5(3xOCH3), 103.4(OCHzO), 105.1 (c-6), 106.0(C-2'), 109.6"109.7(C-4,C-12), 111.5(C-7'), 112.6(C-4a'), 113.2(C-9'), 121.OIC-1'), 121.8(C-5'), 122.4(C-16), 124.4(C-9), 125.6(C-4b'1, 126.1 (C-6'), 127.91C-11 ), 129.0(C-15), 132.3)C-8), 133.81C-3a), 134.31C-5), 136.1 (C-10'), 142.6(C-7a), 145.6(C-7), 146.6(C-14), 147.7(C-4'), 148.61C-13), 149.0(C-3'), 152.2(C-2), 158.8(C-8'), 169.7(CO). E1MS mlz (rel.int.): 615[M]+(100), 584(12), 583(11), 308(25), 292(14), 285(10). 14 0 a Cadinyl eupomatenoid-7 (Compound 28) Oil (3.5 mg). TLC:Rf0.78(S-1); anisaldehyde:grey. [a]o+39.degree.(C.0.3). lRvm~x cm ' :3019, 2917,1614,1599,1505,1481,1450. UV Timex nmllogs): 235(4.45), 265(4.48), 31 1 (4.39). ' H NMR:d0.77(3H,d,J =7Hz,Me-13' or Me- 14'1, 0.90(3H,d,J=7Hz,Me-13' or Me-14'), 1.25(3H,s,Me-15'), 1.71 (3H,s,Me-11'), CA 02298677 2000-O1-31 W0~99/06388 PCT/GB98/02317 32 1.92(3H,dd,J, =6.5,J2=1.SHz,Me-101, 2.43(3H,s,Me-3), 3.90(3H,s,OMe-13), 4.04(3H,s,OMe-7), 5.53( 1 H,br s,H-4'), 6.2211 H,dq,J, =16,J2 = 6.5Hz,H-9), 6.51 (1 H,dq,J, = 16,J2=1.SHz,H-8),6.83(1 H,d,J = 2Hz,H-6),7.04(1 H,d,J=8Hz,H- 1 5), 7.0511 H,d,J =2Hz,H-4), 7.2611 H,dd,J, =8,J2=2Hz,H-12), 7.32(1H,d,J=2Hz,H-16). '3C NMR:d9.7(Me-3), 15.11Me-13'l, 18.41Me-10), 18.5(Me-15'), 21.5lMe-14@1, 21.9(C-9'1, 23.1 (C-1'), 23.9(Me-1 1'), 25.9(C- 12'1, 31.0(C-2'), 37.7(C-8'), 40.2(C-5'), 46.3(C-6'), 48.OIC-10'), 55.8,56.1 (2xOMe), 84.9(C-9'1, 104.7(C-6), 109.2(C-41, 110.9(C-12), 111.8(C-3), 119.2(C-16), 122.4(C-4'), 124.41C-9), 125.8(C-151, 127.1 (C-111, 131.51C-81, 133.1 (C-3a1, 133.7(C-51, 135.2(C-3'), 142.31C-7a), 144.9(C-14), 151.4(C-2), 154,5(C-13). DCIMS m/z (rel.int.):529[M+H]+(41), 528(14), 367(161, 326(11), 325(51), 324(1001, 206(15), 2051931, 20316). (2R 4S) 2 Hvdroxv-6-methoxv-4 7-dimethvl-1-tetralone (Compound 34) Amorphous (17 mg). TLC:Rf0.44(S-1 ); anisaidehyde:yellow. (a]p-39.degree.(c.01 ). CDamax nmf~E):220( + 3.74), 270(-2.09), 295( + 3.52), 315(-143). IRvmax cm ':3496(OH), 3016,1674,(CO),1609,1497. UV ~lmex nm(loge1:225(4.12), 274(4.09). 'H NMRf250 MHz):d1 .46(3H,d,J = 6.5Hz,Me-e), 1 76(1 H,ddd,J, = 1 3.5, Jz=J3= 12.5Hz, H-3ax), 2.21 (3H,br s,Me-7), 2.48( 1 H,ddd,J, = 12.5, JZ=J3=5.5Hz,H-38q), 3.16(1 H,m,H-4), 3.91 (3H,s,OMel, 4.33(1 H,dd,J, =13.5, JZ=5.5Hz,H-2ax), 6.77(1 H,br s,H-5), 7.84(1 H,br d,J=1 Hz,H-8). "C NMR(60MHz):d15.71Me-7), 20.51Me-4), 31.6(C-4), 40.8(C-3), 55.5(OMeI, 73.0(C-2), 107.0(C-5), 122.8(C-8a), 126.1 (C-7), 129.7(C-8), 149.OIC-4a), 162.9(C-6), 198.5(CO). EIMS m/z (rel.int.):220(M]+(68), 202(25), 177(19), 176(100), 175(61), 174(31), 159(12), 148(33), 147(14), 133(37), 117(14), 115(13). EXAMPLE 2 DETERMINATION OF MUTAGENIC AND ANTIMUTAGENIC ACTIVITY The four major constituents of the benzene extract from Aristolochia taliscana roots - eupomatenoid-7 (7), eupomatenoid-1 (81, eupomatenoid-8 (17), Licarin-A (16) - were tested for their mutagenic and antimutagenic properties using the Ames bio-assay (Maron, D.M. and Ames, B.N., Mutation Research, 1983, 113, CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 33 173). The test compounds have the following structural formula: Rx Eupomatenoid-1: Rx & Ry = OCH20, dotted line = double bond Eupomatenoid-7: Rx = OH, Ry = OCH3, dotted line = double bond Eupomatenoid-8: Rx & RY = OCHzO, dotted line = single bond Licarin-A: Rx = OH, R" = OCH3, dotted line = single bond Method Salmonella typhimurium strain TA 100 was used as the test organism and 2-amino-anthracene (2-AA) and 2-nitrofluorene (2-NF) as standard mutagens, of which 1,ug were added to each test plate. In the experiments with 2-AA, "S9 Mix" (derived from Phenobarbital treated rat liver cells (De Flora, S., Camoirana, A., D'Agostini, F. and Balansky, R., Mutation Research, 1992, 267, 183) was also added. Results None of the tested substances showed any mutagenic activity. Eupomatenoid-7 (7) exhibited strong antimutagenic effects against 2- aminoanthracene as well as against 2-nitrofluorene (Tab. 4). Licarin-A (16) and eupomatenoid-1 (8) were found to be antimutagenically active only in the experiment against 2-AA but not against 2-NF (Tab. 5). However, eupomatenoid-8 (17) did not show any antimutagenic effect in the test systems used (Tab. 6). CA 02298677 2000-O1-31 W 0-99/06388 PCT/GB98/02317 34 Eu~omatenoid-7 (71 Residual mutagenic activity (%) observed for: Amount of compound added 2-AA 2-NF [Ng) 50 4 16 100 0 0 Table 4: Results from the experiments on antimutagenic activity of eupomatenoid-7 (71. ~ t~-Licarin-A (6) Residual mutagenic activity (%) observed for Amount of compound added 2-AA 2-NF (,ug) 50 31 94 100 6 85 Table 5: Results from the experiments on antimutagenic activity of ( ~ )- licarin- A (6) Eupomatenoid-1 (81 Residual mutagenic activity (%1 observed for Amount of compound added 2-AA 2-NF (,ug) 50 49 99 100 44 93 Table 6: Results from the experiments on antimutagenic activity of eupomatenoid-1 (8) CA 02298677 2000-O1-31 W0 99/06388 PCT/GB98I02317 Eupomatenoid-8 (17) Residual mutagenic activity 1%) observed for Amount of compound added 2-AA 2-NF (~.ig) 50 90 100 100 73 95 Table 7: Results from the experiments on antimutagenic activity of eupomatenoid-8 (17). EXAMPLE 4 CYTOTOXICITY STUDIES The cytotoxicity of compounds isolated from Aristoiochia Taliscana was assayed using the well known brine shrimp bioassay. The cytotoxicities of compounds of the invention, expressed as percentage "death rates" after 24 hours, at varying concentrations, are shown in Table 8 below. Table 8' Cvtotoxicities of Compounds in the Brine Shrimp Assay "Death LCSo Rate" After 24 Hours (%) i SUBSTANCE l0ppm 100ppm 500ppm (ppm) Aristolactam B (3) '5 9 29 > 500 Aristolactam C (4) 0 0 3 > 500 Eupomatenoid-7 (7) 27 38 38 > 500 Eupomatenoid-1 (8) 12 16 20 > 500 Licarin-A (161 93 93 96 < 10 Eupomatenoid-8 (17) 9 27 42 > 500 Dihydrocarinatidine 26 53 80 ca. 120 (21) Coniferyl alcohol 0 0 15 > 500 (29) Vanillin (31 ) 5 0 12 > 500 Compound 34 52 86 100 < 10 E-Germacrene D (381 0 39 100 ca. 126 Podophyllotoxin 74 93 100 < 10 CA 02298677 2000-O1-31 WO 99/06388 PCT/GB98/02317 36 EXAMPLE 5 ANTIFUNGAL ACTIVITY The antifungal activities of compounds of the invention was determined using a plate diffusion method. Plates containing medium and a fungal species were made up and 150 microgramme aliquots of a test compound of the invention were spotted onto the plate. The diameter of inhibition of fungal growth around the test compound was then determined. The results of the tests are shown in Table 9 below. Table 9: Antifungal Activity Test Microorganism C O M PO U N D Botryis RhizocioniaSapro%gnia cineraa soiani asierophora Aristolactam B (3) - + - Aristoiactam C (4) + + + + Eupomatenoid-7 17) - - - Eupomatenoid-1 (81 - - - Licarin-A (16) - + + - Eupomatenoid-8 (171 - - - Dihydrocarinatidine + + + (21) Coniferyl alcohol - - - 1291 Vanillin (31 f - - - Compound 34 + + + + + + E-Germacrene D (38) + + - - = no inhibition + = 5mm diameter inhibition + + = 5-l0mm diameter inhibition