Books
in black and white
Main menu
Home About us Share a book
Books
Biology Business Chemistry Computers Culture Economics Fiction Games Guide History Management Mathematical Medicine Mental Fitnes Physics Psychology Scince Sport Technics
Ads

Solid-phase organik syntheses - Burdges K.

Burdges K. Solid-phase organik syntheses - John Wiley & Sons, 2000. - 283 p.
ISBN 0-471-22824-9
Download (direct link): phaseorganicsynthesis2000.pdf
Previous << 1 .. 75 76 77 78 79 80 < 81 > 82 >> Next

Manipulations of compound 77 facilitated incorporation of three additional points of diversity (to 78 and 79). These were (i) Sonogashira coupling of terminal alkynes to the aryl iodide functionality; (ii) addition of primary amines to selectively open the lactone; and (iii) use of carboxylic acids to esterify the resulting alcohol. The chemistry was cleverly designed to avoid protecting-group manipulations. Photochemical cleavage of the products from the solid support gave the primary amides 79. This reaction sequence was adapted to split-pool methods giving a 2.18-million-member library. Analysis of this library via nanodroplet assay techniques gave compounds showing selectivity toward TNF activation.
8.12. CONCLUSIONS
The solid-phase syntheses of natural products and natural product derivatives that have been reported to date illustrate several different approaches to the challenge of preparing libraries of bioactive products. Total syntheses
264 RECENT ADVANCES IN SOLID-PHASE SYNTHESIS OF NATURAL PRODUCTS
of complex materials are possible. Derivatization of highly functionalized intermediates is another approach. It is even possible to derivatize a natural product, giving a supported scaffold that can be used to prepare totally different materials that look as if they are natural products that have not yet been discovered.
Arguments that are frequently made to justify natural product synthesis (e.g., leads to methodological developments) can certainly be made in this field. Several interesting methods, some of which feature the resin as an integral part, have been developed in the course of these syntheses.* Moreover, and perhaps unlike some solution-phase syntheses, these works have well-defined practical applications. Products of significant numbers of compounds having likely looking structures tend to lead to biological hits. This field will undoubtedly undergo significant expansion in the next decade.
REFERENCES
1. Gordon, E. ̀.; Kerwin, J. F., Eds. Combinatorial Chemistry and Molecular Diversity in Drug Discovery; Wiley: New York 1998.
2. Lebl, M. Parallel Personal Comments on “Classical” Papers in Combinatorial Chemistry, J. Comb. Chem. 1999, 7,3.
3. Booth, S.; Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. C. Solid-Phase Organic Reactions III: A Review of the Literature Nov 96-Dec 97, Tetrahedron 1998, 54, 15385.
4. Brown, R. C. D. Recent Developments in Solid-Phase Organic Synthesis. J. Chem. Soc. Perkin Trans. 11998, 3293.
5. Bunin, B. A., Ed. The Combinatorial Index. Academic: San Diego, Ñ A, 1998.
6. Hirschman, R. Medicinal Chemistry in the Golden Age of Biology: Lessons from Steroid and Peptide Research, Angew. Chem. Int. Ed. Eng. 1991, 30, 1278.
7. Hung, D. ̉.; Jamison, T. F.; Schrieber, S. L. Understanding and Controlling the Cell Cycle with Natural Products, Chem. Biol. 1996, J, 623.
8. Collins, P. W. Synthesis of Therapeutically Useful Prostaglandin and Prostaglandin Analogs, Chem. Rev. 1993, 93, 1533.
9. Chen, S.; Janda, K. D. Synthesis of Prostaglandin E2 Methyl Ester on a Soluble-Polymer Support for the Construction of Prostanoid Libraries, J. Am. Chem. Soc. 1997, /79, 8724.
REFERENCES 265
10. Chen, S.; Janda, K. D. Total Synthesis of Naturally Occurring Prostaglandin F2a on a Non-Cross-Linked Polystyrene Support, Tetrahedron Lett. 1998, 39,3943.
11. Suzuki, ̀.; Morita, Y.; Koyano, H.; Koga, ̀.; Noyori, R. Three-Component Coupling Synthesis of Prostaglandins. A Simplified, General Procedure, Tetrahedron 1990, 46, 4809.
12. Yonehara, H., Ed. Peptide Chemistry. Protein Research Foundation: Osaka, 1979.
13. Thompson, L. A.; Ellman, J. A. Straightforward and General Method for Coupling Alcohols to Solid Supports, Tetrahedron Lett. 1994, 35, 9333.
14. Thompson, L. A.; Moore, F. L.; Moon, Y.-C.; Ellman, J. A. Solid-Phase Synthesis of Diverse E- and F-Series Prostaglandins, J. Org. Chem. 1998, 63,2066.
15. Farrall, M. J.; Frechet, J. M. J. Bromination and Lithiation: Two Important Steps in the Functionalization of Polystyrene Resins, J. Org. Chem. 1976, 47, 3877.
16. Dess, D. B.; Martin, J. C. Readily Accessible 12-1-5 Oxidant for the Conversion of Primary and Secondary Alcohols to Aldehydes and Ketones, J. Org. Chem. 1983, 48, 4155.
17. Johnson, C. R.; Braun, ̀. P. A Two-Step, Three-Component Synthesis of PGEi: Utilization of a-Iodoenones in Pd(0)-Catalyzed Cross-Couplings of Organoboranes, J. Am. Chem. Soc. 1993, 775, 11014.
18. Dewitt, S. H.; Kiely, J. S.; Stankovic, C. J.; Schroeder, ̀. C.; Cody, D. M. R.; Pavia, M. R. “Diversomers”: An Approach to Nonpeptide, Nonoli-gomeric Chemical Diversity, Proc. Natl. Acad. Sci. USA 1993, 90, 6909.
19. Synthesis of epothilones A and  in solid and solution phase. Nicolaou, K.
C.; Winssinger, N.; Pastor, J.; Ninkovic, S.; Sarabia, F.; He, Y.; Vourloumis,
D.; Yang, Z.; Li, ̉.; Giannakakou, P.; Hamel, E. Nature 1997, 387, 268.
20. Grubbs, R. H.; Miller, S. J.; Fu, G. C. Ring-Closing Metathesis and Related Processes in Organic Synthesis, Acc. Chem. Res. 1995, 28, 446.
Previous << 1 .. 75 76 77 78 79 80 < 81 > 82 >> Next