Function-oriented synthesis, step economy, and drug design

Accounts of Chemical Research

Volumn 41, Issue 1, 2008, Pages 40-49

  Wender, Paul A ^a   Verma, Vishal A ^a   Paxton, Thomas J ^a   Pillow, Thomas H ^a  

^a STANFORD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BIOLOGICAL FACTOR; DRUG CARRIER;

CHEMISTRY; CONFORMATION; DRUG DESIGN; ECONOMICS; NEOPLASM; REVIEW; STEREOISOMERISM; SYNTHESIS;

ANTINEOPLASTIC AGENTS; BIOLOGICAL FACTORS; DRUG CARRIERS; DRUG DESIGN; MOLECULAR CONFORMATION; NEOPLASMS; STEREOISOMERISM;

EID: 38949138457     PISSN: 00014842     EISSN: None     Source Type: Journal    
DOI: 10.1021/ar700155p     Document Type: Review

References (64)

1. (a) Wender, P. A.; Miller, B. L. Toward the Ideal Synthesis: Connectivity Analysis and Multibond-Forming Processes. In Organic Synthesis: Theory and Applications; Hudlicky, T., Ed.; JAI Press: Greenwich, CT, 1993; pp 27-66.
2. (b) Wender, P. A.; Handy, S. T.; Wright, D. L. Towards the Ideal Synthesis. Chem. Ind. 1997, 765-769.
3. (c) Wender, P. A.; Croatt, M. P.; Witulski, B. New Reactions and Step Economy. The Total Synthesis of (+/-)-Salsolene Oxide Based on the Type II. Transition Metal-Catalyzed Intramolecular [4 + 4] Cycloaddition. Tetrahedron 2006, 62, 7505-7511.
4. (a) Lopanik, N.; Lindquist, N.; Targett, N. Potent Cytotoxins Produced by a Microbial Symbiont Protect Host Larvae from Predation. Oecologia 2004, 139, 131-139.
5. (b) Sudek, S.; Lopanik, N. B.; Waggoner, L. E.; Hildebrand, M.; Anderson, C.; Liu, H. B.; Patel, A.; Sherman, D. H.; Haygood, M. G. Identification of the Putative Bryostatin Polyketide Synthase Gene Cluster from " Candidatus Endobugula sertula", the Uncultivated Microbial Symbiont of the Marine Bryozoan Bugula neritina. J. Nat. Prod. 2007, 70, 67-74.
6. Smith, L.; Mann, J. E.; Harris, K.; Miller, M. F.; Brashears, M. M. Reduction of Escherichia coli O157:H7 and Salmonella in Ground Beef using Lactic Acid Bacteria and the Impact on Sensory Properties. J. Food Prot. 2005, 68, 1587-1592.
7. Greene, M. J.; Gordon, D. M. Structural Complexity of Chemical Recognition Cues Affects the Perception of Group Membership in the Ants Linephithema humile and Aphaenogaster cockerelli. J. Exp. Biol. 2007, 210, 897-905.
8. Huffman, M. A. Self-Medicative Behavior in the African Great Apes: An Evolutionary Perspective into the Origins of Human Traditional Medicine. Bioscience 2001, 51, 651-661.
9. Appendino, G.; Szallasi, A. Euphorbium: Modern Research on Its Active Principle, Resiniferatoxin, Revives in Ancient Medicine. Life Sci. 1997, 60, 681-696.
10. Essack, S. Y. The Development of β-Lactam Antibiotics in Response to the Evolution of β-Lactamases. Pharm. Res. 2001, 18, 1391-1399.
11. (a) Eguchi, M. Recent Advances in Selective Opioid Receptor Agonists and Antagonists. Med. Res. Rev. 2004, 24, 182-212.
12. (b) Holt, D. A.; Konialian, A. L.; Brandt, M.; Levy, M. A.; Bossard, M. J.; Luengo, J. I.; Newmann-Tarr, T.; Badger, A. Structure-Activity Studies of Nonmacrocyclic Rapamycin Derivatives. Biorg. Med. Chem. Lett. 1993, 3, 1977-1980.
13. Compiled from an ACS website search for "Total Synthesis" and "Total Syntheses" in the title of publications. Publications on approaches to a total synthesis were not counted.
14. Newman, D. J.; Cragg, G. M. Natural Products as Sources of New Drugs over the Last 25 Years. J. Nat. Prod. 2007, 70, 461-477.
15. Wender, P. A.; Koehler, K. F.; Sharkey, N. A.; Dellaquila, M. L.; Blumberg, P. M. Analysis of the Phorbol Ester Pharmacophore on Protein Kinase C as a Guide to the Rational Design of New Classes of Analogs. Proc. Natl. Acad. Sci. U.S.A. 1986, 83, 4214-4218.
16. Dempsey, E. C.; Newton, A. C.; Mochly-Rosen, D.; Fields, A. P.; Reyland, M. E.; Insel, P. A.; Messing, R. O. Protein Kinase C Isozymes and the Regulation of Diverse Cell Responses. Am. J. Physiol. 2000, 279, L429-L438.
17. Mackay, H. J.; Twelves, C. J. Protein Kinase C: A Target for Anticancer Drugs. Endocr.-Relat. Cancer 2003, 10, 389-396, and references cited therein.
18. Manning, G.; Whyte, D. B.; Martinez, R.; Hunter, T.; Sudarsanam, S. The Protein Kinase Complement of the Human Genome. Science 2002, 298, 1912-1934.
19. Taylor, S. S.; Radzio-Andzelm, E. Protein Kinase Inhibition: Natural and Synthesis Variations on a Theme. Curr. Opin. Chem. Biol. 1997, 1, 219-226.
20. Wender, P. A.; Rice, K. D.; Schnute, M. E. The First Formal Asymmetric Synthesis of Phorbol. J. Am. Chem. Soc. 1997, 119, 7897-7898.
21. Marquez, V. E.; Blumberg, P. M. Synthetic Diacylglycerols (DAG) and DAG-Lactones as Activators of Protein Kinase C (PKC). Acc. Chem. Res. 2003, 36, 434-443.
22. Towle, M. J.; Salvato, K. A.; Budrow, J.; Wels, B. F.; Kuznetsov, G.; Aalfs, K. K.; Welsh, S.; Zheng, W. J.; Seletsky, B. M.; Palme, M. H.; Habgood, G. J.; Singer, L. A.; DiPietro, L. V.; Wang, Y.; Chen, J. J.; Quincy, D. A.; Davis, A.; Yoshimatsu, K.; Kishi, Y.; Yu, M. J.; Littlefield, B. A. In Vitro and in Vivo Anticancer Activities of Synthetic Macrocyclic Ketone Analogues of Halichondrin B. Cancer Res. 2001, 61, 1013-1021.
23. Walensky, L. D.; Kung, A. L.; Escher, I.; Malia, T. J.; Barbuto, S.; Wright, R. D.; Wagner, G.; Verdine, G. L.; Korsmeyer, S. J. Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix. Science 2004, 305, 1466-1470.
24. Shair, M. D.; Yoon, T. Y.; Mosny, K. K.; Chou, T. C.; Danishefsky, S. J. The Total Synthesis of Dynemicin a Leading to Development of a Fully Contained Bioreductively Activated Enediyne Prodrug. J. Am. Chem. Soc. 1996, 118, 9509-9525.
25. Wender, P. A.; Zercher, C. K. Studies on DNA-Cleaving Agents Synthesis of a Functional Dynemicin Analogue. J. Am. Chem. Soc. 1991, 113, 2311-2313.
26. Posner, G. H.; O'Neill, P. M. Knowledge of the Proposed Chemical Mechanism of Action and Cytochrome P450 Metabolism of Antimalarial Trioxanes Like Artemisinin Allows Rational Design of New Antimalarial Peroxides. Acc. Chem. Res. 2004, 37, 397-404.
27. Roth, B. D. The Discovery and Development of Atorvastatin, a Potent Novel Hypolipidemic Agent. Prog. Med. Chem. 2002, 40, 1-22.
28. Miller, E. W.; Tulyanthan, O.; Isacoff, E. Y.; Chang, C. J. Molecular Imaging of Hydrogen Peroxide Produced for Cell Signaling. Nat. Chem. Biol. 2007, 3, 263-267.
29. Meggers, E.; Atilla-Gokcumen, G. E.; Bregman, H.; Maksimoska, J.; Mulcahy, S. P.; Pagano, N.; Williams, D. S. Exploring Chemical Space with Organometallics: Ruthenium Complexes as Protein Kinase Inhibitors. Synlett 2007, 1177-1189.
30. Wall, N. R.; Mohammad, R. M.; Al-Katib, A. M. Bax:Bcl-2 Ratio Modulation by Bryostatin 1 and Novel Antitubulin Agents Is Important for Susceptibility to Drug Induced Apoptosis in the Human Early Pre-B Acute Lymphoblastic Leukemia Cell Line, Reh. Leuk. Res. 1999, 23, 881-888.
31. Elgie, A. W.; Sargent, J. M.; Alton, P.; Peters, G. J.; Noordhuis, P.; Williamson, C. J.; Taylor, C. G. Modulation of Resistance to Ara-C by Bryostatin in Fresh Blast Cells from Patients with AML. Leuk. Res. 1998, 22, 373-378.
32. Oz, H. S.; Hughes, W. T.; Rehg, J. E.; Thomas, E. K. Effect of CD40 Ligand and Other Immunomodulators on Pneumocystis Carinii Infection in Rat Model. Microb. Pathog. 2000, 29, 187-190.
33. Ajani, J. A.; Jiang, Y. X.; Faust, J.; Chang, B. C. B.; Ho, L.; Yao, J. C.; Rousey, S.; Dakhil, S.; Cherny, R. C.; Craig, C; Bleyer, A. A Multi-Center Phase II Study of Sequential Paclitaxel and Bryostatin-1 (NSC 339555) in Patients with Untreated, Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. Invest. New Drugs 2006, 24, 353-357.
34. Alton, D. L.; Epstein, H.; Kuzirian, A.; Bennett, M. C.; Nelson, T. J. Protein Synthesis Required for Long-Term Memory Is Induced by PKC Activation on Days before Associative Learning. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 16432-16437.
35. Schaufelberger, D. E.; Koleck, M. P.; Beutler, J. A.; Vatakis, A. M.; Alvarado, A. B.; Andrews, P.; Marzo, L. V.; Muschik, G. M.; Roach, J.; Ross, J. T.; Lebherz, W. B.; Reeves, M. P.; Eberwein, R. M.; Rodgers, L. L.; Testerman, R. P.; Snader, K. M.; Forenza, S. The Large-Scale Isolation of Bryostatin 1 from Bugula neritina Following Current Good Manufacturing Practices. J. Nat. Prod. 1991, 54, 1265-1270.
36. (a) Ohmori, K.; Ogawa, Y.; Obitsu, T.; Ishikawa, Y.; Nishiyama, S.; Yamamura, S. Total Synthesis of Bryostatin 3. Angew. Chem., Int. Ed. 2000, 39, 2290-2294.
37. (b) Evans, D. A.; Carter, P. H.; Carreira, E. M.; Charette, A. B.; Prunet, J. A.; Lautens, M. Total Synthesis of Bryostatin 2. J. Am. Chem. Soc. 1999, 121, 7540-7552.
38. (c) Kageyama, M.; Tamura, T.; Nantz, M. H.; Roberts, J. C.; Somfai, P.; Whritenour, D. C.; Masamune, S. Synthesis of Bryostatin 7. J. Am. Chem. Soc. 1990, 112, 7407-7408.
39. (d) Keck, G. E.; Welch, D. S.; Poudel, Y. B. Synthetic Studies Toward Bryostatin 1: Preparation of a C(1)-C(16) Fragment by Pyran Annulation. Tetrahedron Lett. 2006, 47, 8267-8270 and references therein.
40. Wender, P. A.; DeBrabander, J.; Harran, P. G.; Jimenez, J. M.; Koehler, M. F. T.; Lippa, B.; Park, C. M.; Siedenbiedel, C.; Pettit, G. R. The Design, Computer Modeling, Solution Structure, and Biological Evaluation of Synthetic Analogs of Bryostatin 1. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 6624-6629.
41. Wender, P. A.; Baryza, J. L.; Brenner, S. E.; Clarke, M. O.; Craske, M. L.; Horan, J. C.; Meyer, T. Function Oriented Synthesis: The Design, Synthesis, PKC Binding and Translocation Activity of a New Bryostatin Analog. Curr. Drug Discovery Technol. 2004, 1, 1-11.
42. Wender, P. A.; Mayweg, A. V. W.; VanDeusen, C. L. A Concise, Selective Synthesis of the Polyketide Spacer Domain of a Potent Bryostatin Analogue. Org. Lett. 2003, 5, 277-279.
43. Wender, P. A.; Verma, V. A. Design, Synthesis, and Biological Evaluation of a Potent, PKC Selective, B-Ring Analog of Bryostatin. Org. Lett. 2006, 8, 1893-1896.
44. Smith, A. B.; Razler, T. M.; Meis, R. M.; Pettit, G. R. Design and Synthesis of a Potent Phorboxazole C(11-15) Acetal Analogue. Org. Lett. 2006, 8, 797-799.
45. Wender, P. A.; Baryza, J. L.; Bennett, C. E.; Bi, C.; Brenner, S. E.; Clarke, M. O.; Horan, J. C.; Kan, C.; Lacote, E.; Lippa, B.; Nell, P. G.; Turner, T. M. The Practical Synthesis of a Novel and Highly Potent Analogue of Bryostatin. J. Am. Chem. Soc. 2002, 124, 13648-13649.
46. Wender, P. A.; Horan, J. C. Synthesis and PKC Binding of a New Class of A-Ring Diversifiable Bryostatin Analogues Utilizing a Double Asymmetric Hydrogenation and Cross-Coupling Strategy. Org. Lett. 2006, 8, 4581-4584.
47. Wender, P. A.; Horan, J. C.; Verma, V. A. Total Synthesis and Initial Biological Evaluation of New B-Ring-Modified Bryostatin Analogs. Org. Lett. 2006, 8, 5299-5302.
48. Wender, P. A.; Baryza, J. L.; Hilinski, M. K.; Horan, J. C.; Kan, C.; Verma, V. A. In Drug Discovery Research: New Frontiers in the Post-Genomic Era; Huang, Z., Ed.; Wiley-VCH: Hoboken, NJ, 2007; pp 127-162.
49. Quinoa, E.; Kakou, Y.; Crews, P. Fijianolides Polyketide Heterocycles from a Marine Sponge. J. Org. Chem. 1988, 53, 3642-3644.
50. Mooberry, S. L.; Tien, G.; Hernandez, A. H.; Plubrukarn, A.; Davidson, B. S. Laulimalide and Isolaulimalide, New Paclitaxel-Like Microtubule-Stabilizing Agents. Cancer Res. 1999, 59, 653-660.
51. Pryor, D. E.; O'Brate, A.; Bilcer, G.; Diaz, J. F.; Wang, Y. F.; Wang, Y.; Kabaki, M.; Jung, M. K.; Andreu, J. M.; Ghosh, A. K.; Giannakakou, P.; Hamel, E. The Microtubule Stabilizing Agent Laulimalide Does Not Bind in the Taxoid Site, Kills Cells Resistant to Paclitaxel and Epothilones, and May Not Require Its Epoxide Moiety for Activity. Biochemistry 2002, 41, 9109-9115.
52. (a) Wender, P. A.; Hegde, S. G.; Hubbard, R. D.; Zhang, L. Total Synthesis of (-)-Laulimalide. J. Am. Chem. Soc. 2002, 124, 4956-4957.
53. For a review, see: (b) Mulzer, J.; Ohler, E. Microtubule-Stabilizing Marine Metabolite Laulimalide and Its Derivatives: Synthetic Approaches and Antitumor Activity. Chem. Rev. 2003, 103, 3753-3786.
54. Wender, P. A.; Hilinski, M. K.; Skaanderup, P. R.; Soldermann, N. G.; Mooberry, S. L. Pharmacophore Mapping in the Laulimalide Series: Total Synthesis of a Vinylogue for a Late-Stage Metathesis Diversification Strategy. Org. Lett. 2006, 8, 4105-4108.
55. Wender, P. A.; Hegde, S. G.; Hubbard, R. D.; Zhang, L.; Mooberry, S. L. Synthesis and Biological Evaluation of (-)-Laulimalide Analogues, Org. Lett. 2003, 5, 3507-3509.
56. Mooberry, S. L.; Randall-Hlubek, D. A.; Leal, R. M.; Hegde, S. G.; Hubbard, R. D.; Zhang, L.; Wender, P. A. Microtubule-Stabilizing Agents Based on Designed Laulimalide Analogues. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 8803-8808.
57. Clark, E. A.; Hills, P. M.; Davidson, B. S.; Wender, P. A.; Mooberry, S. L. Laulimalide and Synthetic Laulimalide Analogues Are Synergistic with Paclitaxel and 2-Methoxyestradiol. Mol. Pharm. 2006, 3, 457-467.
58. Frankel, A. D.; Pabo, C. O. Cellular Uptake of the Tat Protein from Human Immunodeficiency Virus. Cell 1988, 55, 1189-1194.
59. Vives, E.; Brodin, P.; Lebleu, B. A Truncated HIV-1 Tat Protein Basic Domain Rapidly Translocates through the Plasma Membrane and Accumulates in the Cell Nucleus. J. Biol. Chem. 1997, 272, 16010-16017.
60. Wender, P. A.; Mitchell, D. J.; Pattabiraman, K.; Pelkey, E. T.; Steinman, L.; Rothbard, J. B. The Design, Synthesis, and Evaluation of Molecules that Enable or Enhance Cellular Uptake: Peptoid Molecular Transporters. Proc. Natl. Acad. Sci. USA 2000, 97, 13003-13008.
61. Wender, P. A.; Jessop, T. C.; Pattabiraman, K.; Pelkey, E. T.; VanDeusen, C. L. An Efficient, Scalable Synthesis of the Molecular Transporter Octaarginine via a Segment Doubling Strategy. Org. Lett. 2001, 3, 3229-3232.
62. Goun, E. A.; Pillow, T. H.; Jones, L. R.; Rothbard, J. B.; Wender, P. A. Molecular Transporters: Synthesis of Oligoguanidinium Transporters and Their Application to Drug Delivery and Real-Time Imaging. ChemBioChem 2006, 7, 1497-1515.
63. Wender, P. A.; Goun, E. A.; Jones, L. R.; Pillow, T. H.; Rothbard, J. B.; Shinde, R.; Contag, C. H. Real-Time Analysis of Uptake and Bioactivatable Cleavage of Luciferin-Transporter Conjugates in Transgenic Reporter Mice. Proc. Natl. Acad. Sci. USA. 2007, 104, 10340-10345, and references cited therein.
64. Mitchell, D. J.; Kim, D. T.; Steinman, L.; Fathman, C. G.; Rothbard, J. B. Polyarginine Enters Cells More Efficiently than Other Polycationic Homopolymers. J. Pept. Res. 2000, 56, 318-325.