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Current Organic Chemistry

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ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

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Research Article

Evaluation of Different Synthetic Routes to (2R,3R)-3-Hydroxymethyl-2-(4-hydroxy- 3-methoxyphenyl)-1,4-Benzodioxane-6-Carbaldehyde

Author(s): Renáta Kertiné Ferenczi, Tünde-Zita Illyés, Sándor Balázs Király, Gyula Hoffka, László Szilágyi, Attila Mándi, Sándor Antus* and Tibor Kurtán*

Volume 23, Issue 26, 2019

Page: [2960 - 2968] Pages: 9

DOI: 10.2174/1385272823666191212113407

Price: $65

Abstract

The reported enantioselective synthesis for the preparation of (+)-(2R,3R)-2-(4- hydroxy-3-methoxyphenyl)-3-hydroxymethyl-1,4-benzodioxane-6-carbaldehyde, precursor for the stereoselective synthesis of bioactive flavanolignans, could not be reproduced. Thus, the target molecule was prepared via the synthesis and separation of diastereomeric O-glucosides. TDDFT-ECD calculations and the 1,4-benzodioxane helicity rule were utilized to determine the absolute configuration. ECD calculations also confirmed that the 1Lb Cotton effect is governed by the helicity of the heteroring, while the higher-energy ECD transitions reflect mainly the orientation of the equatorial C-2 aryl group.

Keywords: 1, 4-benzodioxane, flavanolignans, stereoselective synthesis, absolute configuration, TDDFT-ECD calculation, hydroxymethyl.

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[1]
Schindler, H. Active substances in pharmaceutical plants; methods to determine plant tinctures; contributions to a supplementary issue of the homoiopathic pharmacopeia. Arzneimittelforschung, 1952, 2(6), 291-296.
[PMID: 12977653]
[2]
Saller, R.; Meier, R.; Brignoli, R. The use of silymarin in the treatment of liver diseases. Drugs, 2001, 61(14), 2035-2063.
[http://dx.doi.org/10.2165/00003495-200161140-00003] [PMID: 11735632]
[3]
Cavallini, L.; Bindoli, A.; Siliprandi, N. Comparative evaluation of antiperoxidative action of silymarin and other flavonoids. Pharmacol. Res. Commun., 1978, 10(2), 133-136.
[http://dx.doi.org/10.1016/S0031-6989(78)80071-X] [PMID: 652840]
[4]
Varga, Z.; Czompa, A.; Kakuk, G.; Antus, S. Inhibition of the superoxide anion release and hydrogen peroxide formation in PMNLs by flavonolignans. Phytother. Res., 2001, 15(7), 608-612.
[http://dx.doi.org/10.1002/ptr.879] [PMID: 11746843]
[5]
Scambia, G.; De Vincenzo, R.; Ranelletti, F.O.; Panici, P.B.; Ferrandina, G.; D’Agostino, G.; Fattorossi, A.; Bombardelli, E.; Mancuso, S. Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin. Eur. J. Cancer, 1996, 32A(5), 877-882.
[http://dx.doi.org/10.1016/0959-8049(96)00011-1] [PMID: 9081370]
[6]
Pelter, A.; Hänsel, R. The structure of silybin (silybum substance E6), the first flavanolignan. Tetrahedron Lett., 1968, 9, 2911-2916.
[http://dx.doi.org/10.1016/S0040-4039(00)89610-0]
[7]
Wagner, H.; Hörhammer, L.; Münster, R. Zur Chemie des silymarins (silybin), des wirkprinzips der früchte von Silybum marianum (L.) Gaertn. (Carduus marianus L.). Arzneimittelforschung, 1968, 18(6), 688-696.
[PMID: 5755805]
[8]
Vogel, G. Natural substances with effects on the liver. In: New Natural Products and plant Drugs with pharmacological, Biological or Therapeutical Activity; Springer: Berlin, Heidelberg, 1977; pp. 249-265.
[http://dx.doi.org/10.1007/978-3-642-66682-7_11]
[9]
Wagner, H.; Diesel, P.; Seitz, M. The chemistry and analysis of silymarin from Silybum marianum Gaertn. Arzneimittelforschung, 1974, 24(4), 466-471.
[PMID: 4408125]
[10]
Arnone, A.; Merlini, L.; Zanarotti, A. Constituents of Silybum marianum. Structure of isosilybin and stereochemistry of silybin. J. Chem. Soc. Chem. Commun. 16, 1979, 696-697.
[http://dx.doi.org/10.1039/c39790000696]
[11]
Szilági, I.; Tétényi, P.; Antus, S.; Seligmann, O.; Chari, V.M.; Seitz, M.; Wagner, H. Struktur von silandrin und silymonin, zwei neuen flavanolignanen aus einer weißblühenden Silybum marianum Varietät. Planta Med., 1981, 43(2), 121-127.
[http://dx.doi.org/10.1055/s-2007-971488] [PMID: 17402024]
[12]
Samu, Z.; Nyiredy, S.; Baitz-Gács, E.; Varga, Z.; Kurtán, T.; Dinya, Z.; Antus, S. Structure elucidation and antioxidant activity of (-)-isosilandrin isolated from Silybum marianum L. Chem. Biodivers., 2004, 1(11), 1668-1677.
[http://dx.doi.org/10.1002/cbdv.200490125] [PMID: 17191807]
[13]
Freudenberg, K.; Neish, A.C. Constitution and biosynthesis of lignins, 1st ed; Springer-Verlag Berlin Heidelberg, 1968.
[http://dx.doi.org/10.1007/978-3-642-85981-6]
[14]
Schrall, R.; Becker, H. Callus- und suspensionskulturen von Silybum marianum. Planta Med., 1977, 32, 27-32.
[http://dx.doi.org/10.1055/s-0028-1097554]
[15]
Erdtmann, H. Dehydrierungen in der coniferylreihe. II. Dehydrodi-isoeugenol. Justus Liebigs Ann. Chem., 1933, 503, 283-294.
[http://dx.doi.org/10.1002/jlac.19335030116]
[16]
Quercia, V.; Pierini, N.; Incarnato, G.; Papetti, P.; Gambero, P. HPLC evaluation of the ratio between the antihepatotoxic constituents of Silybum marianum. Fitoterapia, 1980, 51, 297-301.
[17]
Nyiredy, S.Z.; Szücs, Z.; Antus, S.; Samu, Z.S. New components from Silybum marianum L. fruits: a theory comes true. Chromatographia, 2008, 68, 5-11.
[http://dx.doi.org/10.1365/s10337-008-0722-3]
[18]
Martinelly, E.M.; Morazzoni, P.; Livio, S.; Uberti, E. Liquid chromatographic assay of silybin in human plasma and urine. J. Liq. Chromatogr., 1991, 14, 1285-1296.
[http://dx.doi.org/10.1080/01483919108049321]
[19]
Weyhenmeyer, R.; Mascher, H.; Birkmayer, J. Study on dose-linearity of the pharmacokinetics of silibinin diastereomers using a new stereospecific assay. Int. J. Clin. Pharmacol. Ther. Toxicol., 1992, 30(4), 134-138.
[PMID: 1572758]
[20]
Rickling, B.; Hans, B.; Kramarczyk, R.; Krumbiegel, G.; Weyhenmeyer, R. Two high-performance liquid chromatographic assays for the determination of free and total silibinin diastereomers in plasma using column switching with electrochemical detection and reversed-phase chromatography with ultraviolet detection. J. Chromatogr. B Biomed. Appl., 1995, 670(2), 267-277.
[http://dx.doi.org/10.1016/0378-4347(95)00168-9] [PMID: 8548017]
[21]
Kim, N-C.; Graf, T.N.; Sparacino, C.M.; Wani, M.C.; Wall, M.E. Complete isolation and characterization of silybins and isosilybins from milk thistle (Silybum marianum). Org. Biomol. Chem., 2003, 1(10), 1684-1689.
[http://dx.doi.org/10.1039/b300099k] [PMID: 12926355]
[22]
Lee, D.Y.; Liu, Y. Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J. Nat. Prod., 2003, 66(9), 1171-1174.
[http://dx.doi.org/10.1021/np030163b] [PMID: 14510591]
[23]
Mokhtari, M.J.; Motamed, N.; Shokrgozar, M.A. Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line. Cell Biol. Int., 2008, 32(8), 888-892.
[http://dx.doi.org/10.1016/j.cellbi.2008.03.019] [PMID: 18538589]
[24]
Singh, R.P.; Agarwal, R. Mechanisms and preclinical efficacy of silibinin in preventing skin cancer. Eur. J. Cancer, 2005, 41(13), 1969-1979.
[http://dx.doi.org/10.1016/j.ejca.2005.03.033] [PMID: 16084079]
[25]
Antus, S.; Baitz-Gács, E.; Bauer, R.; Gottsegen, A.; Seligmann, O.; Wagner, H. Regioselective synthesis of 2- and 3-aryl-1,4-benzodioxanes. Liebigs Ann. Chem., 1989, 1989(12), 1147-1151.
[http://dx.doi.org/10.1002/jlac.198919890286]
[26]
Kónya, K.; Ferenczi, R.; Czompa, A.; Kiss-Szikszai, A.; Kurtán, T.; Antus, S. Kinetic resolution of 2-hydroxymethyl-1,4-benzodioxanes by Pseudomonas fluorescens. Arcivoc, 2008, 3, 200-210.
[27]
Chen, X.; Ren, X.; Peng, K.; Pan, X.; Chan, A.S.C.; Yang, T-K. A facile enantioselective approach to neolignans. Tetrahedron Asymmetry, 2003, 14, 701-704.
[http://dx.doi.org/10.1016/S0957-4166(03)00085-5]
[28]
Sharpless, K.B.; Amberg, W.; Bennani, Y.L.; Crispino, G.A.; Hartung, J.; Jeong, K.S.; Kwong, H.L.; Morikawa, K.; Wang, Z.M.; Xu, D.; Zhang, X.L. The osmium-catalyzed asymmetric dihydroxylation: a new ligand class and a process improvement. J. Org. Chem., 1992, 57, 2768-277.
[http://dx.doi.org/10.1021/jo00036a003]
[29]
Gu, W.; Chen, X.; Pan, X.; Chan, A.S.C.; Yang, T-K. First enantioselective syntheses of (2R, 3R)- and (2S, 3S)-3-(4-hydroxy-3-methoxyphenyl)-2-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde. Tetrahedron Asymmetry, 2000, 11, 2801-2807.
[http://dx.doi.org/10.1016/S0957-4166(00)00234-2]
[30]
Mitsunobu, O. The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products. Synthesis, 1981, 1981(1), 1-28.
[http://dx.doi.org/10.1055/s-1981-29317]
[31]
McDonald, B.R.; Nibbs, A.E.; Scheidt, K.A. A biomimetic strategy to access the silybins: total synthesis of (-)-isosilybin A. Org. Lett., 2015, 17(1), 98-101.
[http://dx.doi.org/10.1021/ol503303w] [PMID: 25517432]
[32]
Madaj, J.; Trynda, A.; Jankowska, M.; Wiśniewski, A. Side products of glycosidation with selected 2-acetamido-2-deoxy-D-glucopyranosides. Carbohydr. Res., 2002, 337(16), 1495-1498.
[http://dx.doi.org/10.1016/S0008-6215(02)00207-0] [PMID: 12204611]
[33]
Zemplén, G.; Kunz, A. Über die natriumverbindungen der glucose und die verseiferung der acylierten zucker. Ber. Dtsch. Chem. Ges., 1923, 56, 1705-1710.
[http://dx.doi.org/10.1002/cber.19230560736]
[34]
Kurtán, T.; Antus, S.; Pescitelli, G. Electronic CD of benzene and other aromatic chromophores for determination of absolute configuration. In: Comprehesive Chiroptical Spectroscopy; Berova, N.; Polavarapu, P.L.; Nakanishi, K.; Woody, R.W., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2012; Vol. 2, pp. 73-114.
[http://dx.doi.org/10.1002/9781118120392.ch3]
[35]
Mándi, A.; Kurtán, T. Applications of OR/ECD/VCD to the structure elucidation of natural products. Nat. Prod. Rep., 2019, 36(6), 889-918.
[http://dx.doi.org/10.1039/C9NP00002J] [PMID: 31139804]
[36]
Li, W-S.; Mándi, A.; Liu, J-J.; Shen, L.; Kurtán, T.; Wu, J. Xylomolones A-D from the Thai mangrove Xylocarpus moluccensis: assignment of absolute stereostructures and unveiling a convergent strategy for limonoid biosynthesis. J. Org. Chem., 2019, 84(5), 2596-2606.
[http://dx.doi.org/10.1021/acs.joc.8b03037] [PMID: 30719915]
[37]
Ariantari, N.P.; Ancheeva, E.; Wang, C.; Mándi, A.; Knedel, T-O.; Kurtán, T.; Chaidir, C.; Müller, W.E.G.; Kassack, M.U.; Janiak, C.; Daletos, G.; Proksch, P. Indole diterpenoids from an endophytic Penicillium sp. J. Nat. Prod., 2019, 82(6), 1412-1423.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00723] [PMID: 31117519]
[38]
Li, H-L.; Li, X-M.; Mándi, A.; Antus, S.; Li, X.; Zhang, P.; Liu, Y.; Kurtán, T.; Wang, B-G. Characterization of cladosporols from the marine algal-derived endophytic fungus Cladosporium cladosporioides EN-399 and configurational revision of the previously reported cladosporol derivatives. J. Org. Chem., 2017, 82(19), 9946-9954.
[http://dx.doi.org/10.1021/acs.joc.7b01277] [PMID: 28853887]
[39]
Chai, J.D.; Head-Gordon, M. Systematic optimization of long-range corrected hybrid density functionals. J. Chem. Phys., 2008, 128(8)084106
[http://dx.doi.org/10.1063/1.2834918] [PMID: 18315032]
[40]
Brémond, É.; Savarese, M.; Su, N.Q.; Pérez-Jiménez, Á.J.; Xu, X.; Sancho-García, J.C.; Adamo, C. Benchmarking density functionals on structural parameters of small-/medium-sized organic molecules. J. Chem. Theory Comput., 2016, 12(2), 459-465.
[http://dx.doi.org/10.1021/acs.jctc.5b01144] [PMID: 26730741]
[41]
Peverati, R.; Truhlar, D.G. Communication: A global hybrid generalized gradient approximation to the exchange-correlation functional that satisfies the second-order density-gradient constraint and has broad applicability in chemistry. J. Chem. Phys., 2011, 135(19)191102
[http://dx.doi.org/10.1063/1.3663871] [PMID: 22112059]
[42]
El-Kashef, D.H.; Daletos, G.; Plenker, M.; Hartmann, R.; Mándi, A.; Kurtán, T.; Weber, H.; Lin, W.; Ancheeva, E.; Proksch, P. Polyketides and a dihydroquinolone alkaloid from a marine-derived strain of the fungus Metarhizium marquandii. J. Nat. Prod., 2019, 82(9), 2460-2469.
[http://dx.doi.org/10.1021/acs.jnatprod.9b00125] [PMID: 31432669]
[43]
MacroModel, Schrödinger, LLC, 2012.Available at:. http://www.schrodinger.com/MacroModel (Accessed on 24th June, 2019).
[44]
Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.P.; Izmaylov, A.F.; Bloino, J.; Zheng, G.; Sonnenberg, J.L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J.A.J.; Peralta, J.E.; Ogliaro, F.; Bearpark, M.; Heyd, J.J.; Brothers, E.; Kudin, K.N.; Staroverov, V.N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J.C.; Iyengar, S.S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J.M.; Klene, M.; Knox, J.E.; Cross, J.B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R.E.; Yazyev, O.; Austin, A.J.; Cammi, R.; Pomelli, C.; Ochterski, J.W.; Martin, R.L.; Morokuma, K.; Zakrzewski, V.G.; Voth, G.A.; Salvador, P.; Dannenberg, J.J.; Dapprich, S.; Daniels, A.D.; Farkas, Ö.; Foresman, J.B.; Ortiz, J.V.; Cioslowski, J.; Fox, D.J. Gaussian 09, revision E.01; Gaussian, Inc.: Wallingford, CT, 2013.
[45]
Stephens, P.J.; Harada, N. ECD cotton effect approximated by the Gaussian curve and other methods. Chirality, 2010, 22(2), 229-233.
[PMID: 19408332]
[46]
Varetto, U. Swiss National Supercomputing Centre; MOLEKEL, v. 5.4. Manno, Switzerland,. , 2009.

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