Aspects of Chirality in Natural Products Drug Discovery

Chirality in Drug Research

Volumn 33, Issue , 2006, Pages 67-94

  Krastel, Philipp ^a   Petersen, Frank ^a   Roggo, Silvio ^a   Schmitt, Esther ^a   Schuffenhauer, Ansgar ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Active on nervous system; Biological activity; Chirality; Drug research; Epimerization in vivo; Natural products; Stereochemical aspects; Stereochemical control in biosynthesis; Synthesis; Tubuline stabilizing agents

Indexed keywords

BIOACTIVITY; CHIRALITY; CONTROL SYSTEM SYNTHESIS; SYNTHESIS (CHEMICAL);

DRUG RESEARCH; IN-VIVO; NATURAL PRODUCTS; STABILIZING AGENTS; STEREOCHEMICAL ASPECTS; STEREOCHEMICAL CONTROL;

DRUG PRODUCTS;

EID: 85018195977     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527609437.ch3     Document Type: Chapter

References (100)

1. Kamil, W. M., Dewick, P. M., Biosynthesis of Podophyllum lignans. Part 3. Bio-synthesis of the lignans a-and b-peltatin, Phytochemistry 1986, 25, 2089-92.
2. Puri, S. C., Sida, A., Gupta, R., Gupta, V. K., Handa, G., Srivastava, T. N., Somal, P., Seasonal variation in natural taxoids of north-western Himalaya, J. Med. Aromatic Plant Sci. 2001, 23, 612-616.
3. Yan, X. F., Wang, Y., Yu, T., Zhang, Y. H., Dai, S. J., Variation in camptothecin content in Camptotheca acuminata leaves, Bot. Bull. Acad. Sin. 2003, 44, 99-105.
4. Cragg, G. M., Newman, D. J., Discovery and development of antineoplastic agents from natural sources, Cancer Invest. 1999, 17, 153-163.
5. Cragg, G. M., Newman, D. J., Snader, K. M., Natural Products in Drug Discovery and Development, J. Nat. Prod. 1997, 67, 52-60.
6. Harvey, A., Strategies for discovering drugs from previously unexplored natural products, DDT 2000, 5, 294-300.
7. Newman D. J, Cragg, G. M., Snader, K. M., Natural Products as Sources of New Drugs over the Period 1981-2002, J. Nat. Prod. 2003, 66, 1022-1037.
8. Shen, J., Xu, X., Cheng, F., Liu, H., Lao, X., Shen, J, Chen, K., Zhao, W., Shen, X., Jiang, H., Virtual Screening on Natural Products for Discovering Active Compounds and Target Information, Curr. Med. Chem. 2003, 10, 2327-2342.
9. Buss, A. D., Cox, B., Waigh, R. D., Natural products as leads for new pharmaceuticals in: Burger's Medicinal Chemistry & Drug Discovery Volume 1, Abraham, D. J. (Ed.), John Wiley & Sons, Hoboken, 2003, pp. 847-900.
10. J. Y., Ganesan, A., Natural products and combinatorial chemistry: back to the future, Curr. Opin. Chem. Biol. 2004 8, 271-280.
11. Henkel, T., Brunne, R. M., Müller, H., Reichel, F., Statistical investigation into the structural complementarity of natural products and synthetic compounds, Angew. Chem. Int. Ed. 1999, 38, 643-647.
12. Lee, M. L., Schneider, G., Scaffold architecture and pharmacophoric properties of natural products and trade drugs: application in the design of natural product-based combinatorial libraries, J. Comb. Chem. 2001, 3, 284-289.
13. Feher, M., Schmidt J. M., Property distributions: differences between drugs, natural products and molecules from combinatorial chemistry, J. Chem. Inf. Comput. Sci. 2003, 43, 218-227.
14. CRC Dictionary of Natural Products, v 12.2, CRC Press, http://www.crcpress.com.
15. Retrieved 09. July 2004 from the integrated taxonomic information system (IT IS), http://itis.usda.gov.
16. Pipeline Pilot v 4.0, Scitegic Inc http://www.scitegic.com.
17. Turner, W. B., Aldridge, D. C., Fungal Metabolites II, Academic Press, London, 1983.
18. Buss, A. D., Cox, B., Waigh, R. D., Natural products as leads for new pharmaceuticals in: Burger's Medicinal Chemistry & Drug Discovery Volume 1, Abraham, D. J. (Ed.), John Wiley & Sons, Hoboken, 2003, pp. 847-900.
19. Blinov, K. A., Carlson, D., Elyashberg M. E., Martin, G. E., Martirosian, E. R., Molodtsov, S., Williams, A. J., Computer-assisted structure elucidation of natural products with limited 2D NMR data: application of the StrucEluc system, Magn. Reson. Chem. 2003, 41, 359-372.
20. Steibeck, Ch., Recent developments in automated structure elucidation of natural products, Nat. Prod. Rep. 2004, 21, 512-518.
21. Alvarez, J. C., High throughput docking as a source of novel drug leads, Curr. Opin. Chem. Biol. 2004, 8, 365-370.
22. Rychnovsky, S. D., Griesgraber, G., Schlegel, R., Stereochemical assignment of Roflamycin by 13C Acetonide Analysis, J. Am. Chem. Soc. 1994, 116, 2623-2624.
23. Riccio, R., Bifulco, G., Cimino, P., Bassarello, C., Gomez-Paloma, L., Stereo-chemical analysis of natural products. Approaches relying on the combination of NMR spectroscopy and computational methods, Pure Appl. Chem. 2003, 75, 295-308.
24. Su, B. N., Park, E. J., Mbwambo, Z. H., Santarsiero, B. D., Mesecar, A. D., Fong, H. H. S., Pezzuto, J. M., Kinghorn, A. D., New chemical constituents of euphorbia quinquecostata and absolute configuration assignment by a convenient Mosher ester procedure carried out in NMR tubes, J. Nat. Prod. 2002, 65, 1278-1282.
25. Allenmark, S. G., Chiroptical methods in the stereochemical analysis of natural products, Nat. Prod. Rep. 2000, 17, 145-155.
26. Bringmann, G., Gulden, K. P., Busemann, S., Calculation of circular dichroism spectra of michellamines A and C, based on a complete conformational analysis, Tetrahedron 2003, 59, 1245-1253.
27. Charan, R. D., McKee, T. C., Boyd, M. R., Thorectandrols C, D, and E, new sesterpenes from the marine sponge Thorectandra sp., J. Nat. Prod. 2002, 65, 492-495.
28. Bijvoet, J. M., Peerdeman, A. F., van Bommel, A. J., Determination of the absolute configuration of optically active compounds by means of X-rays, Nature 1951, 168, 271-272.
29. Flack, H. D., On enantiomorph-plarity estimation, Acta Crystallogr. Sect. A 1983, 39, 876-881.
30. Loiseleur, O., Koch, G., Wagner, T., A practical building block for the synthesis of discodermolide, Org. Proc. Res. Dev. 2004, 8, 597-602.
31. Bonnard, I., Manzanares, I., Rinehart, K. L., Stereochemistry of Kahalalide F, J. Nat. Prod. 2003, 66, 1466-1470.
32. Paterson, I., Florence, G. J., The development of a practical total synthesis of discodermolide, a promising microtubule-stabilizing anticancer agent, Eur. J. Org. Chem. 2003, 2193-2208.
33. Xu, Z., Peng, Y., Ye, T., The total synthesis and stereochemical revision of Yanucamide A, Org. Lett. 2003, 5, 2821-2824.
34. Doekel, S., Marahiel, M. A., Biosyn-thesis of natural products on modular peptide synthetases, Metabol. Eng. 2001, 3, 64-77.
35. Weber, G., Schörgendorfer, K., Schneider-Scherzer, E., Leitner, E., The peptide synthetase catalyzing cyclosporin production in Tolypocladium niveum is encoded by a giant 45.8-kilobase open reading frame, Curr. Genet. 1994, 26, 120-125.
36. Stachelhaus, T., Walsh, C. T., Mutational analysis of the epimerization domain in the initiation module PheATE of gramicidin S synthetase, Biochemistry 2000, 39, 5775-5787.
37. Hoffmann, K., Schneider-Scherzer, E., Kleinkauf, H., Zocher, R., Purification and characterization of eukaryotic ala-nine racemase acting as key enzyme in cyclosporin biosynthesis, J. Biol. Chem. 1994, 269, 12710-12714.
38. Luo, L., Burkart, M.D., Stachelhaus, T., Walsh, C. T., Substrate recognition and selection by the initiation module PheATE of gramicidin S synthetase, J. Am. Chem. Soc. 2001, 123, 11208-11218.
39. Brakhage, A. A., Molecular regulation of beta-lactam biosynthesis in filamentous fungi, Microbiol. Mol. Biol. Rev. 1998, 62, 547-585.
40. Kovacevic, S., Tobin, M. B., Miller, J. R., The beta-lactam biosynthesis genes for isopenicillin N epimerase and desacetoxycephalosporin C synthetase are expressed from a single transcript in Streptomyces clavuligerus, J. Bacteriol. 1990, 172, 3952-3958.
41. Usui, S., Yu, C. A., Purification and properties of isopenicillin N epimerase from Streptomyces clavuligerus, Biochim. Biophys. Acta 1989, 999, 78-85.
42. Ullán, R.V., Casqueiro, J., Bañuelo, O., Fernández, F. J., Gutiérrez, S., Martín, J. F., A novel epimerization system in fungal secondary metabolism involved in the conversion of isopenicillin N into penicillin N in Acremonium chrysogenum, J. Biol. Chem. 2002, 277, 46216-46225.
43. Staunton, J., Weissman, K. J., Polyketide biosynthesis: a millennium review, Nat. Prod. Rep. 2001,18, 380-416.
44. Celmer, W. D., Macrolide stereochemistry. II. Configurational assignments at certain centers in various macrolide antibiotics, J. Am. Chem. Soc. 1965, 87, 1799-1802.
45. Cortéz, J., Haydock, S. F., Roberts, G. A., Bevitt, D. J., Leadlay, P. F., An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea, Nature 1990, 348, 176-178.
46. Holzbaur, I. E., Harris, R. C., Bycroft, M., Cortes, J., Bisang, C., Staunton, J., Rudd, B. A. M., Leadlay, P. F., Molecular basis of Celmer's rules: the role of two ketoreductase domains in the control of chirality by the erythromycin modular polyketide synthase, Chem. Biol. 1999, 6, 189-195.
47. Østergaard, L. H., Kellenberger, L., Cortés, J., Roddis, M. P., Deacon, M., Staunton, J., Leadlay, P. F., Stereochemistry of catalysis by the ketoreductase activity in the first extension module of the erythromycin polyketide synthase, Biochemistry 2001, 41, 2719-2726.
48. Walsh, C. T., Polyketide and nonribosomal peptide antibiotics: modularity and versatility, Science 2004, 303, 1805-1810.
49. August, P. R., Tang, L., Yoon, Y. J., Ning, S., Muller, R., Yu, T.W., Taylor, M., Hoffmann, D., Kim, C. G., Zhang, X., Hutchinson, C. R., Floss, H. G., Bio-synthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699, Chem Biol. 1998, 5, 69-79.
50. McGuire, S. M., Silva, J. C., Casillas, E. G., Townsend, C. A., Purification and characterization of versicolorin B synthase from Aspergillus parasiticus. Catalysis of the stereodifferentiating cyclization in aflatoxin biosynthesis essential to DNA interaction, Biochemistry 1996, 35, 11470-11486.
51. Williams, D. C., Barroll, B. J., Jin, Q., Rithner, C. D., Lenger, S. R., Floss, H. G., Coates, R. M., Williams, R. M., Croteau, R., Intramolecular proton transfer in the cyclization of geranylgeranyl diphosphate to the taxadiene precursor of taxol catalyzed by recombinant taxadiene synthase, Chem. Biol. 2000, 7, 969-977.
52. Walker, K., Long, R., Croteau, R., The final acylation step in taxol biosynthesis: cloning of the taxoid C13-side-chain N-benzoyltransferase from Taxus, Proc. Natl. Acad. Sci. 2002, 99, 9166-9171.
53. Pfeiffer, C. C., Optical isomerism and pharmacological action, a generalization, Science 1956, 124, 29-31.
54. Caner, H., Biedermann, P. U., Agranat, I., Conformational spaces of Cinchona alkaloids, Chirality 2003, 15, 637-645.
55. Pasteur, L., Compt. Rend. 1858, 46, 615-617.
56. Souter, R. W., Chromatographic Separations of Stereoisomers, CRC Press, Florida, 1985.
57. Abderhalden, E., Müller, F., Blood Pressure after Intravenous Injection of l-, d-, and dl-Suprarenaline, Z. Physiol. Chem. 1909, 58, 185-188.
58. Kawasuji, T., Koike, K., Saito, H., Chronotropic effects of optical isomers of ephedrine and methylephedrine in the isolated rat right atria and in vitro assessment of direct and indirect actions on a1-adrenoceptors, Biol. Pharm. Bull. 1996, 19, 1423-1428.
59. Casey, A. A., Dewar, H. D., Cholinergic agonists in The Steric Factor in Medicinal Chemistry, A. A. Casey (Ed.), Plenum Press, New York, 1993, pp. 231-285.
60. Nunes, M. A., Brochmann-Hanssen, E., Hydrolysis and epimerization kinetics of pilocarpine in aqueous solution, J. Pharm. Sci. 1974, 63, 716-721.
61. Fletcher, S. R., Baker, R., Chambers, M. S., Herbert, R. H., Hobbs, S. C., Thomas, S. R., Verrier, H. M., Watt, A. P., Ball, R. G., J. Org. Chem. 1994, 59, 1771-1778.
62. Dukat, M., Glennon, R. A., Cell. Mol. Neurobiol. 2003, 23, 365-378.
63. Tanaka, T., Starke, K., Antagonist/agonist preferring a-adrenoreceptors or a1 and a2-adrenoreceptors, Eur. J. Pharmacol. 1980, 63, 191-194.
64. Patil, P. N., Miller, D. D., Trendelenburg, U., Molecular geometry and adrenergic drug activity, Pharmacol. Rev. 1974, 26, 323-392.
65. Ariens, E. J., Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology, Eur. J. Clin. Pharmacol 1984, 26, 663-668.
66. Dalgaard, L., Racemates and enantiomers in drug research and development, Acta Pharm. 1990, 2, 129-230.
67. Ruffolo, R. R., Chirality in a- and b-adrenoreceptor agonists and antagonists, Tetrahedron 1991, 47, 9953-9980.
68. Casy, A. F., Dissymetric probes of pharmacological receptors in The Steric Factor in Medicinal Chemistry, A. A. Casey (Ed.), Plenum Press, New York, 1993, pp. 231-285.
69. Strader, C. D., Fong, T. M., Tota, M. R., Underwood, D., Structure and function of G-protein coupled receptors, Annu. Rev. Biochem. 1994, 63, 101-132.
70. Patil, P. N., Miller, D. D., Chirality in Medicinal Chemistry, W. J. Lough, I. W. Wainer (Eds.), Blackwell Science Ltd., Victoria, Australia, 2002, pp. 139-178.
71. More, J. C. A., Troop, H. M., Dolman, N. P., Jane, D. E., Structural requirements for novel willardiine derivatives acting as AMPA and kainite receptor antagonists, Br. J. Pharmacol. 2003, 138, 1093-1100.
72. Perola, E., Cellai, L., Lamba, D., Filocamo, L., Brufani, M., Long chain analogs of physostigmine as potential drugs for Alzheimer's disease: new insights into the mechanism of action in the inhibition of acetylcholinesterase, Biochim. Biophys. Acta 1997, 1343, 41-50.
73. Yu, Q., Pei, X. F., Holloway, H. W., Greig, N. H., Brossi, A., Total Syntheses and Anticholinesterase Activities of (3aS)-N(8)-Norphysostigmine, (3aS)-N(8)-Norphenserine, Their Antipodal Isomers, and Other N(8)-Substituted Analogs, J. Med. Chem. 1997, 40, 2895-2901.
74. Orjala, J., Nagle, D. G., Hsu, V., Gerwick, W. H., Antillatoxin: An Exceptionally Ichthyotoxic Cyclic Lipopeptide from the Tropical Cyanobacterium Lyngbya majuscule, J. Am. Chem. Soc. 1995, 117, 8281-8282.
75. Li, W. I., Marquez, B. L., Okino, T., Yokokawa, F., Shioiri, T., Gerwick, W. H., Murray, T. F., Characterization of the preferred stereochemistry for the neuropharmacologic actions of Antillatoxin, J. Nat. Prod. 2004, 67, 559-568.
76. Wu, Y. W., Probing into the mechanism of action, metabolism and toxicity of gossypol by studying its (+)- and (-)-stereo-isomers, J. Ethnopharmacol. 1987, 20, 65-78.
77. Shelley, M. D., Hartley, L., Fish, R. G., Groundwater, P., Morgan, J. J., Mort, D., Mason, M., Evans, A., Stereo-specific cytotoxic effects of gossypol enantiomers and gossypolone in tumor cell lines, Cancer Lett. 1999, 135, 171-180.
78. Terreaux, C., Hostettmann, K., Stereo-chemical issues in bioactive natural products in Stereochemical Aspects of Drug Action and Disposition, Springer-Verlag, Berlin, 2003, pp. 77-90.
79. Robert, A., Nezamis, J.E., Phillips, J. P., Inhibition of gastric secretion by prostaglandins, Am. J. Dig. Dis. 1967, 12, 1073-1076.
80. Newman, A., de Moraes-Filho, J. P., Philippakos, D., Misiewicz, J. J., The effect of intravenous infusions of prostaglandins E-2 and F-2alpha on human gastric function, Gut 1975, 16, 272-276.
81. Robert, A., Magerlein, B. J., 15-Methyl PGE2 and 16,16-dimethyl PGE2. Potent inhibitors of gastric secretion, Adv. Biosci. 1973, 9, 247-253.
82. Merritt, M. V., Bronson, G. E., Baczynskyj, L., Boal, J. R., Oxygen exchange as a function of epimerization of 15(R)- and 15(S)-methylprostaglandin E2. Evidence for asymmetric carbonium ion intermediates, J. Am. Chem. Soc. 1980, 102, 346-351.
83. Merritt, M. V., Bronson, G. E., Kinetics of epimerization of 15(R)-methylprostaglandin E2 and of 15(S)-methylprostaglandin E2 as a function of pH and temperature in aqueous solution, J. Am. Chem. Soc. 1978, 100, 1891-1895.
84. Czibula, L., Nemes, A., Visky, G., Farkas, M., Szombathelyi, Z., Karpati, E., Sohar, P., Kessel, M., Kreidl, J., Syntheses and cardiovascular activity of stereo-isomers and derivatives of eburnane alkaloids, Liebigs Ann. Chem. 1993, 221-229.
85. Bollag, D. M., McQueney, P. A., Zhu, J., Hensens, O., Koupal, L., Liesch, J., Goetz, M., Lazarides, E., Woods, C. M., Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action, Cancer Res. 1995, 55, 2325-2333.
86. Wartmann, M., Altmann, K.-H., The biology and medicinal chemistry of epothilones, Curr. Med. Chem. - Anti Cancer Agents 2002, 2, 123-148.
87. Kowalski, R. J., Giannakakou, P., Hamel, E., Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol?), J. Biol. Chem. 1997, 272, 2534-2541.
88. Altmann, K.-H., Wartmann, M., O'Reilly, T., Epothilones and related structures-a new class of microtubule inhibitors with potent in vivo antitumor activity, Biochim. Biophys. Acta 2000, 1470, M79-M91.
89. Nicolaou, K. C., Vourloumis, D., Li, T., Pastor, J., Winssinger, N., He, Y., Ninkovic, S., Sarabia, F., Vallberg, H., Roschangar, F., King, N. P., Finlay, M. R. V., Giannakakou, P., VerdierPinard, P., Hamel, E., Designed epothilones: combinatorial synthesis, tubulin assembly properties, and cytotoxic action against taxol-resistant tumor cells, Angew. Chem. Int. Ed. 1997, 36, 2097-2103.
90. Nicolaou, K. C., Winssinger, N., Pastor, J., Ninkovic, S., Sarabia, F., He, Y., Vourloumis, D., Yang, Z., Li, T., Giannakakou, P., Hamel, E., Synthesis of epothilones A and B in solid and solution phase, Nature 1997, 387, 268-272.
91. End, N., Bold, G., Caravatti, G., Wartmann, M., Altmann, K.-H., Synthetic epothilone analogs with modifications in the northern hemisphere and the heterocyclic side-chain-synthesis and biological evaluation, Proceedings of ECSOC-4, Sept. 1-30, 2000, http://www.mdpi.org/ecsoc-4.htm.
92. Taylor, R. E., Zajicek, J., Conformational properties of epothilone, J. Org. Chem. 1999, 64, 7224-7228.
93. Taylor, R. E., Chen, Y., Beatty, A., Myles, D. C., Zhou, Y., Conformation-activity relationships in polyketide natural products: a new perspective on the rational design of epothilone analogues, J. Am. Chem. Soc. 2003, 125, 26-27.
94. Carlomagno, T., Blommers, M. J. J., Meiler, J., Jahnke, W., Schupp, T., Petersen, F., Schinzer, D., Altmann, K.-H., Griesinger, C., The high-resolution solution structure of epothilone a bound to tubulin: An understanding of the structure-activity relationships for a powerful class of antitumor agents, Angew. Chem. Int. Ed. 2003, 42, 2511-2515.
95. Rihs, G., Walter, H. R., unpublished results, picture of structure given
96. Longley, R. E., Caddigan D., Harmody D., Gunasekera M., Gunasekera, S. P., Discodermolide - a new, marine-derived immunosuppressive compound. I. In vitro studies, Transplantation 1991, 52, 650-656.
97. Longley, R. E., Caddigan, D., Harmody, D., Gunasekera, M., Gunasekera, S. P., Discodermolide - a new, marine-derived immunosuppressive compound. II. In vivo studies, Transplantation 1991, 52, 656-661.
98. Ter Haar, E., Kowalski, R. J., Hamel, E., Lin, C. M., Longley, R. E., Gunasekera, S. P., Rosenkranz, H. S., Day, B. W., Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol, Biochemistry 1996, 35, 243-250.
99. Mickel, S. J., Niederer, D., Daeffler, R., Osmani, A., Kuesters, E., Schmid, E., Schaer, K., Gamboni, R., Chen, W., Loeser, E., Kinder, F. R., Konigsberger, K., Prasad, K" Ramsey, T. M., Repic, O., Wang, R. M., Florence, G., Lyothier, I., Paterson, I., Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 5: Linkage of Fragments C1-6 and C7-24 and Finale, Org. Proc. Res. Dev. 2004, 8, 122-130.
100. Hung, D. T., Nerenberg, J. B., Schreiber, S. L., Distinct binding and cellular properties of synthetic (+)- and (-)-discodermolides, Chem. Biol. 1994, 1, 67-71.