Novel strategies for the solid phase synthesis of substituted indolines and indoles

Bioorganic and Medicinal Chemistry

Volumn 11, Issue 3, 2003, Pages 465-476

  Nicolaou, K C ^a,b   Roecker, A J ^a   Hughes, Robert ^a   Van Summeren, Ruben ^a   Pfefferkorn, Jeffrey A ^a   Winssinger, Nicolas ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BROMINE DERIVATIVE; INDOLE DERIVATIVE; LIGAND; POLYMER; RESIN;

ARTICLE; CHEMICAL BOND; CHEMICAL MODIFICATION; COMBINATORIAL LIBRARY; CYCLIZATION; DRUG SYNTHESIS; OXIDATION; REDUCTION;

ANILINE COMPOUNDS; COMBINATORIAL CHEMISTRY TECHNIQUES; CYCLIZATION; DRUG DESIGN; FREE RADICALS; INDOLES; OXIDATION-REDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037293566     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0968-0896(02)00386-3     Document Type: Article

References (39)

1. (a) Nicolaou K.C., Hanko R., Hartwig W. Handbook of Combinatorial Chemistry: Vols. 1 and 2:2001;Wiley-VCH, Weinheim, 2001.
2. (b) Gordon K., Balasubramanian S. Curr. Opin. Drug Discovery Dev. 2:1999;342.
3. (c) Balkenhohl F., von dem Bussche-Hunnefeld C., Lansky A., Zechel C. Angew. Chem., Int. Ed. Engl. 35:1996;2288.
4. (d) Veber D.F., Drake F.H., Gowen M. Curr. Opin. Chem. Biol. 1:1997;151.
5. (a) Nicolaou K.C., Pfefferkorn J.A., Roecker A.J., Cao G.-Q., Barluenga S., Mitchell H.J. J. Am. Chem. Soc. 122:2000;9939.
6. (b) Nicolaou K.C., Pfefferkorn J.A., Mitchell H.J., Roecker A.J., Barluenga S., Cao G.-Q., Affleck R.L., Lillig J.E. J. Am. Chem. Soc. 122:2000;9954.
7. (c) Nicolaou K.C., Pfefferkorn J.A., Barluenga S., Mitchell H.J., Roecker A.J., Cao G.-Q. J. Am. Chem. Soc. 122:2000;9968.
8. (a) Nicolaou K.C., Pfefferkorn J.A., Cao G.-Q. Angew. Chem., Int. Ed. 39:2000;734.
9. (b) Nicolaou K.C., Pfefferkorn J.A., Cao G.-Q. Angew. Chem., Int. Ed. 39:2000;739.
10. (c) Nicolaou K.C., Pfefferkorn J.A., Cao G.-Q., Kim S., Kessabi J. Org. Lett. 1:1999;807.
11. For initial studies on solid phase synthesis of nitrogen-containing heterocycles see: (d) Nicolaou K.C., Roecker A.J., Pfefferkorn J.A., Cao G.-Q. J. Am. Chem. Soc. 122:2000;2966.
12. (a) Nicolaou K.C., Pfefferkorn J.A., Schuler F., Roecker A.J., Cao G.-Q. Chem. Biol. 7:2000;979.
13. (b) Nicolaou K.C., Roecker A.J., Barluenga S., Pfefferkorn J.A., Cao G.-Q. ChemBioChem. 6:2001;460.
14. For indapamide see: (a) Lalande A., Roux S., Denne M.-A., Stanley E.R., Schiavi P., Guez D., De Vernejoul M.-C. J. Bone Miner. Res. 16:2001;361.
15. For pravadoline see: (b) Reggio P.H., Basu-Dutt X., Sharmista X., Barnett-Norris J., Castro M.T., Hurst D.P., Seltzman H.H., Roche M.J., Gilliam A.F., Thomas B.F., Stevenson L.A., Pertwee R.G., Abood M.E. J. Med. Chem. 41:1998;5177.
16. For the anticancer agent see: (c) Yoon, S. J.; Chung, Y.; Lee, M. S.; Choi, D. R.; Lee, J. A.; Yun, D. K.; Moon, E. Y.; Hwang, H. S.; Choi, C. H.; Jung, S. H. Patent WO 9807719 (Dong Wha Pharm. Ind. Co., Ltd., S. Korea) [Chem. Abs. 128:204885].
17. For the synthesis of polymer-bound phenylselenenyl bromide resin see: Nicolaou K.C., Pastor J., Barluenga S., Winssinger N. Chem. Commun. 1998;1947.
18. (a) Bermudez J., Dabbs S., Joiner K.A., King F.D. J. Med. Chem. 33:1990;1929.
19. (b) Adachi S., Koike K., Takayanagi I. Pharmacology. 53:1996;250.
20. To the best of our knowledge, this is the first example whereby radical cleavage from a solid support is accompanied by an intramolecular cyclization to afford an additional ring system in the target molecule. Solid phase non-releasing radical cyclizations have been described previously, for representative examples, see: (a) Du, X.; Armstrong, R. W. J. Org. Chem. 1997, 62, 5678. (b) Watanabe, Y.; Ishikawa, S.; Takao, G.; Toru, T. Tetrahedron Lett. 1999, 40, 3411. (c) Miyabe, H.; Tanaka, H.; Naito, T. Tetrahedron Lett. 1999, 40, 8387.
21. To the best of our knowledge, this is the first example whereby radical cleavage from a solid support is accompanied by an intramolecular cyclization to afford an additional ring system in the target molecule. Solid phase non-releasing radical cyclizations have been described previously, for representative examples, see: (a) Du, X.; Armstrong, R. W. J. Org. Chem. 1997, 62, 5678. (b) Watanabe, Y.; Ishikawa, S.; Takao, G.; Toru, T. Tetrahedron Lett. 1999, 40, 3411. (c) Miyabe, H.; Tanaka, H.; Naito, T. Tetrahedron Lett. 1999, 40, 8387.
22. To the best of our knowledge, this is the first example whereby radical cleavage from a solid support is accompanied by an intramolecular cyclization to afford an additional ring system in the target molecule. Solid phase non-releasing radical cyclizations have been described previously, for representative examples, see: (a) Du, X.; Armstrong, R. W. J. Org. Chem. 1997, 62, 5678. (b) Watanabe, Y.; Ishikawa, S.; Takao, G.; Toru, T. Tetrahedron Lett. 1999, 40, 3411. (c) Miyabe, H.; Tanaka, H.; Naito, T. Tetrahedron Lett. 1999, 40, 8387.
23. For solution phase radical-based syntheses of substituted indoles see: (a) Reding M.T., Kaburagi Y., Tokuyama H., Fukuyama T. Heterocycles. 56:2002;313. (b) Ziegler F.E., Harran P.G. J. Org. Chem. 58:1993;2768.
24. For solution phase radical-based syntheses of substituted indoles see: (a) Reding M.T., Kaburagi Y., Tokuyama H., Fukuyama T. Heterocycles. 56:2002;313. (b) Ziegler F.E., Harran P.G. J. Org. Chem. 58:1993;2768.
25. For a recent solid phase synthesis of substituted indoles see: (c) Wu T.Y.H., Ding S., Gray N.S., Schultz P.G. Org. Lett. 3:2001;3827.
26. For solution phase precedent, see: (a) Clive D.L.J., Wong C.K., Kiel W.A., Menchen S.M. J. Chem. Soc. Chem. Commun. 379:1978; (b) Clive D.L.J., Farina V., Singh A., Wong C.K., Kiel W.A., Menchen S.M. J. Org. Chem. 45:1980;2120.
27. For solution phase precedent, see: (a) Clive D.L.J., Wong C.K., Kiel W.A., Menchen S.M. J. Chem. Soc. Chem. Commun. 379:1978; (b) Clive D.L.J., Farina V., Singh A., Wong C.K., Kiel W.A., Menchen S.M. J. Org. Chem. 45:1980;2120.
28. Separation of the desired indoline cleavage products from organotin by-products represents an obstacle to the combinatorial use of this methodology, and as such, new strategies are needed to overcome this problem. The polarity-based approach used here relies on the desired product being protonated and taken into the aqueous phase such that the organotin species can be removed with the organic phase.
29. See Experimental for the synthesis of o-allyl anilines.
30. For the preparation of o-prenylated anilines see: Cooper M.A., Lucas M.A., Taylor J.M., Ward A.D., Williamson N.M. Synthesis. 2001;621.
31. (a) Hamann L.G., Higuchi R.I., Zhi L., Edwards J.P., Wang X.-N., Marschke K.B., Kong J.W., Farmer L.J., Jones T.K. J. Med. Chem. 41:1998;623.
32. (b) Pooley C.L.F., Edwards J.P., Goldman M.E., Wang M.-W., Marschke K.B., Crombie D.L., Jones T.K. J. Med. Chem. 41:1998;3461.
33. (a) Raner K.D., Ward A.D. Aust. J. Chem. 44:1991;1749.
34. (b) Cooper M.A., Francis C.L., Holman J.W., Kasum B., Taverner T., Tiekink E.R.T., Ward A.D. Aust. J. Chem. 53:2000;123.
35. Duncia J.V., Pierce M.E., Santella J.B. III. J. Org. Chem. 56:1991;2395.
36. O'Brien P.M., Sliskovic D.R., Picard J.A., Lee H.T., Purchase C.F. II., Roth B.D., White A.D., Anderson M., Mueller S.B., Bocan T., Bousley R., Hamelehle K.L., Homan R., Lee P., Krause B.R., Reindal J.F., Stanfield R.L., Turluck D. J. Med. Chem. 39:1996;2354.
37. To the best of our knowledge, this represents the first example of the conversion of carbamates to ureas via organoaluminum chemistry (see Experimental for procedure). For an example of the analogous conversion of esters to amides see: Basha, A.; Lipton, M.; Weinreb, S. M. Tetrahedron Lett. 1977, 48, 4171.
38. For previous N-allylaniline Claisen rearrangements see: (a) Anderson W.K., Lai G. Synthesis. 1995;1287 (b) Izumi T., Kasahara A. Heterocyclic Chem. 27:1990;1173.
39. For previous N-allylaniline Claisen rearrangements see: (a) Anderson W.K., Lai G. Synthesis. 1995;1287 (b) Izumi T., Kasahara A. Heterocyclic Chem. 27:1990;1173.