Synthesis of (+/-) - oxohexahydrofuro[3,2-b]pyrroles (pyrrolidine-trans-lactones) using acyl-iminium chemistry

Synlett

Volumn , Issue 12, 1998, Pages 1375-1377

  Macdonald, Simon J F ^a   Spooner, Julie E ^a   Dowle, Michael D ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0042331242     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-1998-1965     Document Type: Article

References (28)

1. Vender, R.L. J. Invest. Med. 1996, 44, 531
2. Ripka, W.C. Curr. Opin. Chem. Biol. 1997, 1, 242.
3. The IUPAC name for pyrrolidine trans-lactones is 5-oxo-hexahydrofuro[3,2-6]pyrroles.
4. (a) Macdonald, S.J.F., Belton, D.J., Buckley, D.M., Spooner, J.E., Anson, M.S., Harrison, L.A., Mills, K., Upton, R.J., Dowle, M.D., Smith, R.A., Risley, C., Molloy, C.J. J. Med. Chem., in press,
5. (b) Dowle, M.D.; Finch, H.; Harrison, L.A.; Inglis, G.G.A.; Johnson, M.R.; Macdonald, S.J.F.; Shah, P.; Smith, R.A. WO 9736903 A1 971009.
6. (a) Thaning, M.; Wistrand, L-G. J. Org. Chem. 1990, 55, 1406.
7. (b) Thaning, M.; Wistrand, L-G. Acta Chem. Scand. 1989, 43, 290.
8. (c) Thaning, M.; Wistrand, L-G. Acta Chem. Scand. 1992, 46, 194.
9. (a) Sunose, M.; Anderson, K.M.; Gallagher, T.; Macdonald, S.J.F. Tetrahedron. Lett. in press.
10. (b) Sugisaka, C.H.; Carroll, P.J.; Correia, C.R.D. Tetrahedron Lett. 1998, 39, 3413.
11. Burgess, L.E.; Gross, E.K.M.; Jurka, J. Tetrahedron Lett. 1996, 37, 3255.
12. 2HCH); assignments were supported by decoupling experiments and warming to 55°C coalesced the signals at δ 5.67 and 5.61, the OH's. The other signals simplify.
13. 2'S of the malonate. Spectroscopic correlation with 20, and the fact that cis-hydroxyester affords spontaneously cis-lactone, supports the trans assignment.
14. 2HCH); assignments supported by decoupling and HMQC experiments.
15. On pyrrolidones: (a) Dai, W-M.; Nagao, Y.; Fujita, E. Heterocycles 1990, 30, 1231 and references therein.
16. (b) Bernadi, A.; Micheli, F.; Potenza, D.; Scolastic, C.; Villa, R. Tetrahedron Lett. 1990, 31, 4949.
17. (c) Koot, W-J.; Ginkel, R.; Kranenburg, M.; Hiemstra, H.; Louwrier, S.; Moolenaar, M.J.; Speckamp, W.N. Tetrahedron Lett. 1991, 32, 401;
18. (d) Pilli, R.A,; Russowsky, D. J. Org.Chem. 1996, 61, 3187. On carbamates of pyrrolidines:
19. (f) Kraus, G.A.; Neueschwander, K. J. Chem. Soc., Chem. Commun., 1982, 134.
20. (g) Asada, S.; Kato, M.; Asai, K.; Ineyama, T.; Nishi, S.; Izawa, K.; Shono, T. J. Chem. Soc., Chem. Commun. 1989, 486;
21. (h) David, M.; Dhimane, H.; Vanucci-Bacque, C.; Llommet, G. Synlett 1998, 206.
22. The mixture of cis and trans diols may indicate the facile formation of an acyl-iminium ion from the cis diol which reacts with water from the less hindered face to give the trans diol, or ring opening of the cyclic aminal and reclosing.
23. The yield was dependent on the mode of work-up and/or the stability of the product to chromatography on silica gel.
24. 4) O to 100% B over 40min with a flow rate of 1mL/min. The α-isomer of 17 and 18 retained at 31.61min and the β-isomer at 31.94min.
25. 3, 55°C) δ 7.40-7.28 (m, 5H), 5.15 (s, 2H), 4.46-4.37 (m, 1H), 4.18-4.05 (m, 2H), 3.99-3.90 (m, 1H), 3.83-3.63 (m, 1H), 3.43-3.30 (m, 1H), 3.15-2.97 (bm, 0.6H), 2.84-2.62 (bm, 0.4H), 2.28-1.13 (m, 10H), 0.85 (t, J = 7Hz, 3H).
26. Inanaga, J.; Katsuki, S.; Takimoto, S.; Ouchida, S.; Inone, K.; Nakano, A.; Okukuda, N.; Yamaguchi, M. Chem. Lett. 1979, 1021.
27. -1.
28. -1.