The Synthesis of Novel Trans-Oxabicyclo[3,3,0]octane Systems as Potential Inhibitors of HIV Protease

Synlett

Volumn 1997, Issue 2, 1997, Pages 193-194

  Mahler, Mikael E ^a   Palmer, Michael J ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0141547128     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-1997-739     Document Type: Article

References (19)

1. See for example, Thaisrivongs, S. Ann. Rep. Med. Chem. 1994, 29, 133-144.
2. Lam, Y. S.; Jadhav, P. K.; Eyermann, C. J.; Hodge, C. N.; Ru, Y.; Bacheler, L. T.; Meek, J. L.; Otto, M. J.; Rayner, M. M.; Wong, N.; Chang, C-H.; Weber, P. C.; Jackson, D. A.; Sharpe, T. R.; Erickson-Viitanen, S. Science 1994, 293, 380-384.
3. Molecular modelling was carried out using Quanta™.
4. Kurosawa, K.; Obara, H. Bull. Chem. Soc. Jpn. 1966, 39, 525-530.
5. Bartlett, P. A.; Green, F. R. J. Amer. Chem. Soc. 1978, 100, 4858-4865.
6. (a) Evans, S. A.; Barry, C. N. J. Org. Chem. 1983, 48, 2825-2828.
7. (b) Evans, S. A.; Barry, C. N. J. Org. Chem. 1983, 46, 3361-3364.
8. (a) Picard, P.; Leclerq, D.; Bats, J.-P.; Moulines, J. Synthesis 1981, 550-551.
9. (b) Takano, T., Satoh, S., Ogasawara, K. Heterocycles 1985, 23, 41-44.
10. 4) and filtered, washing the resin with ethyl acetate. Evaporation of the filtrate in vacuo gave the trans oxabicyclo[3.3.0]octanone 7 as a white solid (0.74g 87%).
11. 13C correlation experiments (one bond and long range) were performed on the oxabicyclooctanol product, indicating the presence of either the trans-fused isomer or a 1:1 mixture of the two cis-fused alternatives with the two CH-OH resonances appearing at the same chemical shift. A NOE between the ring junction hydrogens at δ 2.08 and δ 2.41 proved that they are in the same molecule. A long mixing TOCSY experiment also indicated correlation between the ring junction hydrogens, again supporting their belonging to the same molecule. Thus, the ring junction has a trans configuration.
12. Conia, J. M.; Sandre, J. -P. Bull. Soc. Chim. Fra. 1963, 752-754.
13. (a) Mander, L. N.; Sethi, S. P. Tetrahedron Lett. 1983, 24, 5425-5428.
14. 11a followed by C-alkylation of sodium enolate with benzyl bromide. Attempts to hydrolyse the resulting α,α′-bisbenzylbismethylcarboxylate oxabicyclooctanone were unsuccessful.
15. (a) Yamashita, M.; Matsumiya, K.; Tanabe, M.; Suemitsu, R. Bull. Chem. Soc. Jpn. 1985, 58, 407-408.
16. (b) Corey, E. J.; Enders, D. Tetrahedron Lett. 1976, 1, 3-6.
17. (c) Octanone 7 was condensed with N,N-dimethylhydrazine. Monoalkylation of the resulting hydrazone as the lithium enamine with benzyl bromide was achieved. However, hydrazone acylation attempts with ethyl chloroformate were unsuccessful.
18. Conia, J. M.; Sandre, J. -P. Bull. Soc. Chim. Fra. 1963, 744-752.
19. 1H NMR and examination of the intense cross peaks between spatially close hydrogens in the 2D ROESY spectrum, then enabled assignment of 11 as a single trans diastereomer pair.