Solution phase synthesis of a spiro[pyrrolidine-2,3'-oxindole] library via a three component 1,3-dipolar cycloaddition reaction

Tetrahedron Letters

Volumn 39, Issue 16, 1998, Pages 2235-2238

  Fokas, Demosthenes ^a   Ryan, William J ^a   Casebier, David S ^a   Coffen, David L ^a  

^a ARQULE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PYRROLIDINE DERIVATIVE; SPIRO(PYRROLIDINE 2,3' OXINDOLE); UNCLASSIFIED DRUG;

ARTICLE; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; STEREOCHEMISTRY; STRUCTURE ANALYSIS; SYNTHESIS;

EID: 0032537090     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)00234-2     Document Type: Article

References (16)

1. 1. For reviews, see: (a) Balkenhohl, F.; von dem Bussche-Hünnefeld, C.; Lansky, A.; Zechel, C. Angew. Chem. Int. Ed. Engl. 1996, 35, 2289-2337.
2. (b) Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555-600.
3. 2. Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acct. Chem. Research 1996, 29, 123-131.
4. th ACS National Meeting, Las Vegas, September 1997, Organic Division Abstract #62.
5. 4. A class of spiro-oxindoles has been reported as aldose reductase inhibitors. Fujimori, S. Jap. Pat. Appl. 88-2912; Chem. Abstr. 1990,112: 98409.
6. 4. A class of spiro-oxindoles has been reported as aldose reductase inhibitors. Fujimori, S. Jap. Pat. Appl. 88-2912; Chem. Abstr. 1990,112: 98409.
7. 5. Marx, M. A.; Grillot, A.-L.; Lower, C. T.; Breaver, K. A.; Bartlett, P. A. J. Am. Chem. Soc. 1997, 119, 6153-6167 and references therein.
8. 6. (a) Grigg, R.; Thianpatanagul, S.; J. Chem. Soc., Chem. Commun., 1984, 180-181.
9. (b) Grigg, R.; Aly, M. F.; Shridharan, V.; Thianpatanagul, S. J. Chem. Soc.,Chem. Commun., 1984, 182-183.
10. (c) Ardil, H.; Grigg, R.; Shridharan, V.; Surendrakumar, S.; Thianpatanagul, S.; Kanajun, S. J. Chem. Soc.,Chem. Commun., 1986, 602-604.
11. 7. For an example with chalcone as a dipolarophile, see: Fishwick, C. W. G.; Foster, R. J.; Carr, R. E. Tetrahedron Lett. 1996, 37, 3915-3918.
12. 8. For studies on the mechanism of azomethine ylide formation via the decarboxylative route see: Grigg, R.; Iddle, J.; McMeekin, P.; Surendrakumar, S. J. Chem. Soc., Perkin Trans. I., 1988, 2703-2713.
13. 9. Crystals were grown from methanol and a molecule of methanol was located in the crystal of 4e. We are pleased to acknowledge the contribution to this project provided by Dr. John Huffman and the X-ray crystallography laboratory of Indiana University. (equation presented)
14. 10. Twelve isatins were commercially available. Four other substrates were easily made by alkylation of isatin with benzyl/allyl halides in the presence of DMF and NaH.
15. 11. Kohler, E. P.; Chadwell, H. M. Org. Syn. Coll. Vol. 1, 1941, 78-80.
16. 12. A percentage (25%) of the libray was screened individually through HPLC and mass spectrometry. Reactions involving L-valine, L-glutamine, L-isoleucine or the chalcone prepared from 3-methoxyacetophenone and 3,5-difluorobenzaldehyde were inconsistent.