Solid-Phase Synthesis of β-Sultams

Journal of Organic Chemistry

Volumn 62, Issue 23, 1997, Pages 8177-8181

  Gordeev, Mikhail F ^a,b   Gordon, Eric M ^a,b   Patel, Dinesh V ^a,b  

^a AFFYMAX RESEARCH INSTITUTE   (United States)

^b Versicor Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000677561     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9713316     Document Type: Article

References (24)

1. For some reviews, see: (a) Gallop, M. A.; Barrett, R. W.; Dower, W.J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233-1251. (b) Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385-1401. (c) Gordon, E. M.; Gallop, M. A.; Patel, D. V. Acc. Chem. Res 1996, 29, 9; 144-154. (d) Patel, D. V.; Gordon, E. M. Drug Discovery Today 1996, 1, 134-144.
2. For some reviews, see: (a) Gallop, M. A.; Barrett, R. W.; Dower, W.J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233-1251. (b) Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385-1401. (c) Gordon, E. M.; Gallop, M. A.; Patel, D. V. Acc. Chem. Res 1996, 29, 9; 144-154. (d) Patel, D. V.; Gordon, E. M. Drug Discovery Today 1996, 1, 134-144.
3. For some reviews, see: (a) Gallop, M. A.; Barrett, R. W.; Dower, W.J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233-1251. (b) Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385-1401. (c) Gordon, E. M.; Gallop, M. A.; Patel, D. V. Acc. Chem. Res 1996, 29, 9; 144-154. (d) Patel, D. V.; Gordon, E. M. Drug Discovery Today 1996, 1, 134-144.
4. For some reviews, see: (a) Gallop, M. A.; Barrett, R. W.; Dower, W.J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233-1251. (b) Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. J. Med. Chem. 1994, 37, 1385-1401. (c) Gordon, E. M.; Gallop, M. A.; Patel, D. V. Acc. Chem. Res 1996, 29, 9; 144-154. (d) Patel, D. V.; Gordon, E. M. Drug Discovery Today 1996, 1, 134-144.
5. See, for example, a recent review on solid-phase organic reactions: Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527-4554.
6. For reviews on β-sultams, see: (a) Timberlake, J. W.; Alder, E. S. In Comprehensive Heterocyclic Chemistry, Vol. I; Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press: New York, 1984; p 449. (b) Chanet-Ray, J.; Vessiere, R. Org. Prep. Proced. Int. 1986, 18, 159-178. (c) Harris, P. A. In Comprehensive Heterocyclic Chemistry II, Vol. I; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Elsevier Science Inc.: Oxrford, 1996; p 1009.
7. For reviews on β-sultams, see: (a) Timberlake, J. W.; Alder, E. S. In Comprehensive Heterocyclic Chemistry, Vol. I; Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press: New York, 1984; p 449. (b) Chanet-Ray, J.; Vessiere, R. Org. Prep. Proced. Int. 1986, 18, 159-178. (c) Harris, P. A. In Comprehensive Heterocyclic Chemistry II, Vol. I; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Elsevier Science Inc.: Oxrford, 1996; p 1009.
8. For reviews on β-sultams, see: (a) Timberlake, J. W.; Alder, E. S. In Comprehensive Heterocyclic Chemistry, Vol. I; Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press: New York, 1984; p 449. (b) Chanet-Ray, J.; Vessiere, R. Org. Prep. Proced. Int. 1986, 18, 159-178. (c) Harris, P. A. In Comprehensive Heterocyclic Chemistry II, Vol. I; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Elsevier Science Inc.: Oxrford, 1996; p 1009.
9. For a related solution-phase synthesis, see: (d) Szymonifka, M. J.; Heck, J. V. Tetrahedron Lett. 1989, 30, 2869-2872.
10. Tsuge, O.; Iwanami, S. Bull. Chem. Soc. Jpn. 1970, 43, 3543.
11. Look, G. C.; Holmes, C. P.; Chinn, J. P.; Gallop, M. A. J. Org. Chem. 1994, 59, 7588-7590.
12. 3b sultam products with dilute trifluoroacetic acid.
13. 1H NMR and HPLC analysis of cleaved products in most cases did reveal presence of impurities with exception of clean transformations with alanine. In part, this might be accounted for by a two-step cycloaddition mechanism of the β-sultam formation commencing from the sulfonylation of imines with a reactive sulfonyl halide to generate hydrolytically unstable sulfonyliminium intermediates (cf. ref 3d). The latter may cyclize into β-sultams (in presence of bases) or produce sulfonylated amino acids upon workup (as detected by ESI MS in a crude product of this reaction with benzylidenevaline-functionalized Sasrin resin). In all cases (see Scheme 1, Table 1), β-sultams were detected as principal products and separated by HPLC.
14. Detection at 220 nm. See Experimental Section for details of the HPLC analysis.
15. Holmes, C. P. J. Org. Chem. 1997, 62, 2370.
16. 9 we observed overall cleaner results using 2-propanol that can be easily removed in vacuo prior to HPLC purifications.
17. For a review of early works, see: Pillai, V. N. R. Synthesis 1980, 1-26.
18. (a) Oldenburg, K. R.; Vo, K. T.; Ruhland, B.; Schatz, P. J.; Yuan, Z J. Biomol. Screen. 1996, 1, 123.
19. (b) Schullek, J. R.; Butler, J. H.; Ni, Z.-J.; Chen, D.; Yuan, Z. Anal. Biochem. 1997, in press.
20. 1H NMR spectra of the compounds thus obtained (cf. also refs 3c and 5d). Diastereomeric ratios for most products was in a range of 1:1 to 2.5:1 (see Supporting Information), with the exception of compounds obtained from L-tyrosine tert-butyl ester (Table 1, compound 4f; isomeric ratio of 15:1) and L-serine tert-butyl ether (Table 1, compound 4h; single diastereomer). The reaction with racemic DL-aminocaprylic acid was also diastereoselective, as only two trans diastereomers were obtained. Absolute stereochemistry of major and minor trans diastereomers is not known.
21. Prepared from (chlorosulfonyl)acetyl chloride and (9-fluorenyl)-methyl alcohol (see Experimental Section).
22. 13C NMR (see Experimental Section).
23. Green, J.; Bradley, K. Tetrahedron 1993, 49, 4141-4146.
24. Carpino, L. A.; Han, G. Y. J. Org. Chem. 1972, 37, 3404-3409.