US20030187306A1 - DDQ mediated one step dimerisation of beta-asarone or beta-asarone rich acorus calamus oil in the formation of novel neolignan - Google Patents

DDQ mediated one step dimerisation of beta-asarone or beta-asarone rich acorus calamus oil in the formation of novel neolignan Download PDF

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US20030187306A1
US20030187306A1 US10/108,269 US10826902A US2003187306A1 US 20030187306 A1 US20030187306 A1 US 20030187306A1 US 10826902 A US10826902 A US 10826902A US 2003187306 A1 US2003187306 A1 US 2003187306A1
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neolignan
trimethoxy
phenyl
asarone
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Arun Sinha
Bhupendra Joshi
Ruchi Acharya
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Council of Scientific and Industrial Research CSIR
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Priority to DE60224098T priority patent/DE60224098T2/de
Priority to PCT/IN2002/000073 priority patent/WO2003080551A1/en
Priority to EP02713168A priority patent/EP1487770B1/de
Priority to AT02713168T priority patent/ATE380785T1/de
Priority to JP2003580930A priority patent/JP4266348B2/ja
Application filed by Council of Scientific and Industrial Research CSIR filed Critical Council of Scientific and Industrial Research CSIR
Priority to US10/108,269 priority patent/US20030187306A1/en
Assigned to COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH reassignment COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ACHRAYA, RUCHI, JOSHI, BHUPENDRA PRASAD, SINHA, ARUN KUMAR
Priority to US10/660,556 priority patent/US6969778B2/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
    • C07C43/205—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring
    • C07C43/2055—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring containing more than one ether bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
    • C07C43/215—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring having unsaturation outside the six-membered aromatic rings

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  • the present invention relates to “DDQ mediated one step dimerisation of dihydro product of toxic ⁇ -asarone rich Acorus calamus oil towards formation of novel neolignan: 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene” in which 2,4,5-trimethoxyphenylpropane (a dihydro product of asarone obtained via hydrogenation of ⁇ -asarone rich Acorus calamus oil) of the formula (I), undergoes dimerisation in a single step towards formation of neolignan 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1 propene (named as NEOLASA-I) of the formula II along with biologically active ⁇
  • neolignan (NEOLASA-I) is hydrogenated to obtain its corresponding dihydro product 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy) phenyl-1-(2′,4′,5′-trimethoxy)phenylpropane (named as NEONLASA-II) so as to confirm the structure as well as to determine the position of double bond existing in the above parent neolignan (NEOLASA-I) which may additionally serve as a simple synthon towards preparation of naturally occurring rare neolignans (such as acoradin or magnosalin or heterotropan and phenyl indane derivative) and their analogues in sufficient quantity to have opportunity for a wide range of biological activities including antifungal, antioxidant, antiinflammatory, neuroleptic, antihepatoxic, anticancer, anti-HIV and anti-PAF activities known for structurally similar neolignan derivatives (such as aurein or hexestrol
  • the neolignan (NEOLASA-I) formation is the first example of DDQ assisted one step synthesis of neolignan, a dimer of phenylpropanoid, in good yield (32%) from 2,4,5-trimethoxyphenylpropane derivative.
  • Neolignans and lignans are known for their wide range of biological activities including hapatoprotective, harmone blocking, antibacterial, antifungal, plant growth regulator, anti-HIV, anticancer and antioxidant activities (Macrae, W. D. and Towers, G. H. N., Phytochemistry, 23 (6), 1207-1220 (1984); Ward, R. S., Tetrahedron, 46 (15), 5029-5041 (1990); Charlton, J. L., J. Nat. Prod., 61, 1447-1451 (1998); Alves, C. N.; Barroso, L. P.; Santos, L. S. and Jardim, I. N, J. Braz. Chem.
  • Neolignans and lignans are a large group of natural products characterized by the coupling of two C 6 -C 3 units which are derived from cinnamic acid derivatives, however, both are present in traces in plants (Rao, K. V. and Rao, N. S. P., J. Nat. Prod., 53(1), 212-215 (1990) and Filler, F.; Bail, J. C. L.; Duroux, J. L.; Simon, A. and Chulia, A. J., Planta Medica, 67, 700-704 (2001)).
  • the C 6 -C 3 unit is treated as propylbenzene and numbered from 1 to 6 in the benzene ring from 7 to 9 (or ⁇ to ⁇ ) starting from propyl group. With the second C 6 -C 3 unit the numbers are primed.
  • the compound is referred as a lignan.
  • compound is referred to as neolignan.
  • Dimers with linkages other than this type are known as cycloneolignan, epoxyneolignan and oxyneolignan etc.
  • the presence of a double bond (or triple bond) in the side chain (i.e. C-7 to C-9 or C-7 to C-9) of the lignan, neolignan or epoxyneolignan skeleton is indicated by changing the -ane ending to -ene (or -yne) with a locant to indicate the position of the double bond (Moss, G. P. Pure Appl. Chem., 72 (8), 1493-1523 (2000)).
  • the basic ring system of these neolignans and lignans can be deduced by dimerization of allyl and p-propenylphenols (such as isoeugenol, coniferyl or sinapyl alcohol). Oxidation of phenols often yields phenoxy radicals, which couple with little selectivity. Both C—C and C—O bonds are formed, mainly in ortho- and para-positions to the phenolic hydroxyl. Synthetically useful reactions are obtained only when the reactivity is blocked by substituents in the aforementioned positions. For instance from 2,6- or 2,4-substituted phenols, C—C bonded biphenyls can be obtained in good yields.
  • coupling can be directed by carrying out the reaction intramolecularly, ring closure being an effective way of inducing regioselectivity (Whitting, D. A. Oxidative Coupling of Phenols and Phenol Ethers. In Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I.; Pattenden, G., Eds.; Pergemon: Oxford, Vol. 3, 659-703 (1991)).
  • oxidation of a mixture of two phenols can lead to a mixture of dimers of the individual phenols and cross-coupling products between the different phenols.
  • oxidants such as K 3 Fe(CN) 6 , H 2 O 2 , FeCl 3 , VOF 3 , thallium (III) tristrifluoacetate, horseradish peroxidase, iodobenzene diacetate (Frank, B. and Schlingloff, G., Liebig. Ann. Chem., 659, 132 (1962); Taylor, W. I. and Battersby, A. R. In “Oxidative Couplings of Phenols”, Marcel Dekker, New York (1967); Kametani, T. and Fukumoto, K., Synthesis, 657 (1972); Taylor, E. C.; Andrade, J. G.; Rall, G. J.
  • phenoxy radical or phenoxonium ion intermediate is most common for synthesis of lignans and neolignans but there are a few patents and papers where non-phenolic compounds have been used for the synthesis of lignans and neolignans (Kadota, S.; Tsubono, K. and Makino, K., Tetrahedron Letters, 28 (25), 2857-2860 (1987) and Dhal, R.; Landais, Y.; Lebrun, A.; Lenain, V. and Robin, J. P., Tetrahedron, 50 (4), 1153-1164 (1994)).
  • nordihydroguaiaretic acid one of the most important dimer derived from resinous exudates of many plants
  • pharmacological activities including the inhibition of the human papillomavirus, herpes simplex, HIV and hyperglycemic activity
  • non-phenolic compounds such as dimethoxypropiophenone (Perry, C. W. U.S. Pat. No. 3,769,350 (1975)), substituted benzylmagnesium chloride (Akio, M.; Kohei, T.; Keizo, S. and Makoto, K.
  • the present invention is free from above drawbacks and discloses one step dimerisation of 2,4,5-trimethoxyphenylpropane (a dihydro product of asarone obtained via hydrogenation of ⁇ -asarone rich Acorus calamus oil) of the formula I (Example I) into novel neolignan 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene (named as NEOLASA-I) of the formula II (Example II).
  • NEOLASA-I novel neolignan 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene
  • neolignan (NEOLASA-I) is hydrogenated to obtain its corresponding dihydro product (3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenylpropane) (named as NEONLASA-II) (Example III) so as to confirm the structure as well as to determine the position of double bond existing in the above parent neolignan (NEOLASA-I) of the formula (II) which may additionally serve as a simple synthon towards preparation of naturally occurring rare neolignans (such as acoradin or magnosalin or heterotropan and phenyl indane derivative) and their analogues in sufficient quantity to have opportunity for a wide range of biological activities (Wenkert, E.; Gottling, H.
  • neolignan (3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene or 2,2′,4,4′,5-5′-hexamethoxy-7′,8-neolig-7-ene), ⁇ -asarone and 1-(2,4,5-trimethoxy)phenyl-1-propanone (or isoacoramone) are successfully confirmed on the basis of spectral data (Example II).
  • our invention discloses a simple and economical process for preparing novel neolignans (3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene of the formula (II) and 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenylpropane of the formula (III) along with ⁇ -asarone of formula (IIa), and isoacaromone (2,4,5-trimethoxypropiophenone) of formula (IIb), as side products thereof, starting from relatively cheaper and economical material 2,4,5-trimethoxyphenylpropane obtained via hydrogenation of ⁇ -asarone rich Acorus calamus oil as outlined in Scheme-I.
  • Other objectives and advantages of the present invention will be
  • the main object of the present invention is to prepare 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenylpropene, a neolignan, from 2,4,5-trimethoxyphenylpropane which is, in fact, the hydrogenated product of toxic ⁇ -asarone isolated from commercially available Acorus calamus oil.
  • Another object of the present invention is to utilize toxic ⁇ -asarone rich calamus oil of tetraploid or hexaploid varieties (distributed extensively in Asian countries), thereby, enhancing the profitable use thereof.
  • Still another object of the invention is to study the interaction of 2,4,5-trimethoxyphenylpropane by varying amount of DDQ, time and temperature.
  • Yet another object of the invention is to develop easy purification process to obtain high purity of neolignan and side products.
  • Yet another object of the invention is to establish the structure of side products which finally appeared to be a naturally occurring rare phenylpropanoids namely ⁇ -asarone and 1-(2,4,5-trimethoxy)phenyl-1-propanone.
  • Yet another object of the invention is to further establish the position of the double bond existing in the above neolignan by its reduction into corresponding dihydro neolignan i.e. 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenylpropane.
  • the present invention provides a process for the preparation of neolignan utilizing a mild and efficient reagent 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and 2,4,5-trimethoxyphenylpropane which is, in fact, the hydrogenated product of toxic ⁇ -asarone isolated from commercially available calamus oil.
  • DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
  • 2,4,5-trimethoxyphenylpropane which is, in fact, the hydrogenated product of toxic ⁇ -asarone isolated from commercially available calamus oil.
  • NEOLASA-I novel neolignan (3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene)
  • NEOLASA-I novel neolignan (3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene)
  • two more products which later on were characterized as biologically active, rare, naturally occurring phenylpropanoids namely ⁇ -asarone and 1-(2,4,5-trimethoxyphenyl)-1-propanone (isoacoramone).
  • neolignan (NEOLASA-I) was established by its catalytic hydrogenation into corresponding dihydro neolignan (3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenylpropane) (named as NEOLASA-II).
  • NEOLASA-II dihydro neolignan
  • FIG. 1 is 1 H NMR (300 MHz) spectra of 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene (in CDCl 3 ) of the reaction product of Example II
  • FIG. 2 is 13 C NMR (75.4 MHz) spectra of 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene (in CDCl 3 ) of the reaction product of Example II
  • FIG. 3 is DEPT-135 0 spectra of 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene (in CDCl 3 ) of the reaction product of Example II
  • FIG. 4 is the electro spray (ES) mass spectrum of 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene (MW 416) of the reaction product of Example II
  • FIG. 5 is 1 H NMR (300 MHz) spectra of ⁇ -asarone (in CDCl 3 ) of the reaction product of Example II
  • FIG. 6 is 13 C NMR (75.4 MHz) spectra of ⁇ -asarone (in CDCl 3 ) of the reaction product of Example II
  • FIG. 7 is 1 H NMR (300 MHz) spectra of 1-(2,4,5-trimethoxy)phenyl-1-propanone (in CDCl 3 ) of the reaction product of Example II
  • FIG. 8 is 13 C NMR (75.4 MHz) spectra of 1-(2,4,5-trimethoxy)phenyl-1-propanone (in CDCl 3 ) of the reaction product of Example II
  • FIG. 9 is the electro spray (ES) mass spectrum of 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene (MW 418) of the reaction product of Example III
  • the present invention provides “DDQ mediated one step dimerisation of dihydro product of toxic ⁇ -asarone rich Acorus calamus oil in the formation of novel neolignan: 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene” wherein the said process comprises hydrogenation of toxic ⁇ -asarone or calamus oil containing mixture of ⁇ , ⁇ - and ⁇ -asarone to obtain 2,4,5-trimethoxyphenylpropane of formula I followed by reacting the above said compound with DDQ at a temperature in the range of 5-120° C.
  • neolignan from 2,4,5-trimethoxyphenylpropane, which is, in fact, the hydrogenated product of toxic ⁇ -asarone isolated from commercially available calamus oil.
  • a simple process involves the conversion of mixture of all the three isomeric forms of phenylpropene i.e. ⁇ , ⁇ and ⁇ -asarone firstly into 2,4,5-trimethoxyphenylpropane and then utilizing it as a simple synthon for the preparation of 3-ethyl-2-methyl-1-(2′,4′,5′-trimethoxy)-phenyl)-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-propene and side products ⁇ -asarone and 1-(2,4,5-trimethoxy)phenyl-1-propanone thereof.
  • the molar ratio of DDQ to 2,4,5-trimethoxyphenylpropane is in the range of 2.1:1.0 to 1.0:1.0.
  • novel neolignan as a crystalline solid with melting point ranging from 96°-97 C.
  • NEOLASA-II novel dihydro neolignan i.e. 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenylpropane
  • NEOLASA-II novel dihydro neolignan obtained by catalytic hydrogenation of 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene
  • NEOLASA II novel dihydro
  • trans-isomers e.g. ⁇ -asarone and isoeugenol etc
  • cis/allyl-isomers e.g. ⁇ -asarone and saffrole
  • Acorus calamus family: Araceae
  • tetraploid and hexaploid varieties distributed extensively in Asian countries like India, Japan, Pakistan and China
  • diploid and triploid varieties contain limited amount of ⁇ -asarone (3 to 8%)
  • ⁇ -asarone is experimentally proved to be carcinogenic in animals and has also been found to induce tumors in the duodenal region after oral administration.
  • ⁇ -asarone has also shown chromosome damaging effect on human lymphocytes in-vitro after metabolic activation (Taylor, J. M.; Jones, W. I.; Hogan, E. C.; Gross, M. A.; David, D. A. and Cook, E. L., Toxicol. Appl. Pharmacol., 10, 405 (1967); Keller, K.; Odenthal, K. P. and Leng, P.
  • 2,4,5-trimethoxyphenylpropane (or 1-Propyl-2,4,5-trimethoxybenzene) is tested for the first time as five times less toxic than ⁇ -asarone and thus, this 2,4,5-trimethoxyphenylpropane enables its application in the products such as mouthwashes, tooth pastes, antiseptic soap products, chewing gum flavors and little in spicy products due to its sweet, ylang, slightly spicy and fruity aroma.
  • 2,4,5-trimethoxypropiophenone can be utilized as a simple synthon for the preparation of diarylbutane type lignan as an analogue of nordihydroguaiaretic acid (NDGA acid) which is prepared by dimerization of 4,5-dimethoxypropiophenone (Perry, C. W. U.S. Pat. No. 3,769,350 (1975)).
  • neolignan i.e. 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene) (named as NEOLASA-I) (Example II).
  • neolignan (NEOLASA-I) is hydrogenated (Example III) to obtain its corresponding dihydro product i.e. 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenylpropane (named as NEONLASA-II) so as to confirm the structure as well as to determine the position of double bond existing in the above parent neolignan (NEOLASA-I) which may additionally serve as a simple synthon towards preparation of neolignans derivatives in sufficient quantity to have opportunity for a wide range of biological activities including antifungal, antioxidant, anti-inflammatory, neuroleptic, anti-hepatotoxic, anticancer, anti-HIV and anti-PAF activities known for structurally similar neolignan derivatives.
  • NEONLASA-II 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy
  • Neolignans and lignans comprise a class of natural plant products and they are found in the roots, stems, bark, fruit and seeds of many plant species. More than 200 compounds in this general class have been identified and a great diversity in the chemical assembly of the two characteristic phenylpropanoid units, as well as degree of oxidation and types of substituents is apparent.
  • some natural lignans/neolignans are used as starting materials for the semi-synthesis of biological active compounds such as podophyllotoxin, isolated from Podophyllum species, is used for the semi-synthesis of the anticancer compounds etoposide and teniposide (Stähelin, H. F. and Wartburg, A.
  • neolignas/lignans are found in traces in plant kingdom and for these reasons, several methods of preparation of neolignas/lignans have been developed by several chemists and some of the reported conventional methods include the following:
  • Typical prior art refrences include Iguchi, M., Nishiyama, A., Terada, Y. and Yamamura, S., Tetrahedron, 51, 4511-4514 (1977); McKillop, A.; Turrell, A. G. and Taylor, E. C., J. Org. Chem., 765 (1977); Minato, A.; Tamao, K.; Suzuki, K. and Kumada, M., Tetrahedron Letters, 21, 4017-4020 (1980); Cambie, R. C.; Clark, G. R.; Craw, P. A.; Rutledge, P. S. and Woodgate, P. D., Aust. J.
  • neolignan NEOLASA-I
  • NEOLASA-II dihydro product
  • 2,4,5-trimethoxyphenylpropane (dihydro asarone):
  • the starting material 2,4,5-trimethoxyphenylpropane is prepared by hydrogenation of either ⁇ -asarone (isolated from Acorus calamus oil) or commercially available calamus oil rich in asarones (i.e. ⁇ and/or ⁇ , ⁇ -asarone) content.
  • the combined acetic acid layer was evaporated and mixture was poured into water and extracted with dichloromethane (3 ⁇ 70 mL). The combined organic layer were washed with brine (3 ⁇ 15 mL), 10% sodium bicarbonate (2 ⁇ 10 mL), brine (3 ⁇ 15 mL) and dried over sodium sulphate.
  • the process provides novel neolignan (NEOLASA-I) having one asymmetric center and one double bond in aliphatic side chain which is further capable of undergoing conversion into several naturally occurring neolignan and lignan derivatives.
  • the process provides novel dihydro neolignan i.e. 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenylpropane (NEOLASA-II) by hydrogenation of 3-ethyl-2-methyl-3-(2′′,4′′,5′′-trimethoxy)phenyl-1-(2′,4′,5′-trimethoxy)phenyl-1-propene (NEOLASA-I).
  • the process provides a novel dihydro (NEOLASA II) which is capable of undergoing conversion into several naturally occurring neolignan and lignan derivatives.

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US10/108,269 2002-03-27 2002-03-28 DDQ mediated one step dimerisation of beta-asarone or beta-asarone rich acorus calamus oil in the formation of novel neolignan Abandoned US20030187306A1 (en)

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AU2002244906A AU2002244906A1 (en) 2002-03-27 2002-03-27 Formation of neolignan by ddq mediated dimerisation of dihydroasarone
DE60224098T DE60224098T2 (de) 2002-03-27 2002-03-27 Herstellung eines neolignans mittels durch ddq vermittelte dimerisierung von dihydroasaron
PCT/IN2002/000073 WO2003080551A1 (en) 2002-03-27 2002-03-27 Formation of neolignan by ddq mediated dimerisation of dihydroasarone
EP02713168A EP1487770B1 (de) 2002-03-27 2002-03-27 Herstellung eines neolignans mittels durch ddq vermittelte dimerisierung von dihydroasaron
AT02713168T ATE380785T1 (de) 2002-03-27 2002-03-27 Herstellung eines neolignans mittels durch ddq vermittelte dimerisierung von dihydroasaron
JP2003580930A JP4266348B2 (ja) 2002-03-27 2002-03-27 Ｄｄｑの媒介するジヒドロアサロンの二量体化によるネオリグナンの生成
US10/108,269 US20030187306A1 (en) 2002-03-27 2002-03-28 DDQ mediated one step dimerisation of beta-asarone or beta-asarone rich acorus calamus oil in the formation of novel neolignan
US10/660,556 US6969778B2 (en) 2002-03-27 2003-09-12 DDQ mediated one step dimerization of β-asarone or β-asarone rich Acorus calamus oil in the formation of novel neolignan

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PCT/IN2002/000073 WO2003080551A1 (en) 2002-03-27 2002-03-27 Formation of neolignan by ddq mediated dimerisation of dihydroasarone
US10/108,269 US20030187306A1 (en) 2002-03-27 2002-03-28 DDQ mediated one step dimerisation of beta-asarone or beta-asarone rich acorus calamus oil in the formation of novel neolignan

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US6969778B2 (en) 2005-11-29
WO2003080551A1 (en) 2003-10-02
JP4266348B2 (ja) 2009-05-20
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US20040049085A1 (en) 2004-03-11
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