A concise synthesis of the tricyclic skeleton of pleuromutilin and a new approach to cycloheptenes

Organic Letters

Volumn 5, Issue 3, 2003, Pages 325-328

  Bacqué, Eric ^b   Pautrat, François ^a   Zard, Samir Z ^a  

^a LABORATOIRE DE SYNTHÈSE ORGANIQUE   (France)

^b SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOHEPTENE; PLEUROMUTILIN; XANTHIC ACID DERIVATIVE; CYCLOHEPTANE DERIVATIVE; DITERPENE;

ARTICLE; CHEMICAL REACTION; CYCLIZATION; DRUG SYNTHESIS; REACTION ANALYSIS; CHEMICAL STRUCTURE; CHEMISTRY; SYNTHESIS;

CYCLOHEPTANES; DITERPENES; MOLECULAR STRUCTURE;

EID: 0038518309     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol027312m     Document Type: Article

References (19)

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3. For previous studies concerning the total synthesis of pleuromutilin, see: (a) Kahn, M. Tetrahedron Lett. 1980, 21, 4547. (b) Gibbons, E. G. J. Am. Chem. Soc. 1982, 104, 1767 and references cited therein. (c) Patten, A. H.; Trost, B. M. Diss. Abstr. Int. 1987, 47, 3361-B; Chem. Abstr. 106, 156709. (d) Paquette, L. A.; Pansegrau, P. D.; Wiedeman, P. E.; Springer, J. P. J. Org. Chem. 1988, 53, 1461 and references cited therein. (e) Boeckman R. K., Jr.; Springer, D. M.; Alessi, T. R. J. Am. Chem. Soc. 1989, 111, 8284.
4. For previous studies concerning the total synthesis of pleuromutilin, see: (a) Kahn, M. Tetrahedron Lett. 1980, 21, 4547. (b) Gibbons, E. G. J. Am. Chem. Soc. 1982, 104, 1767 and references cited therein. (c) Patten, A. H.; Trost, B. M. Diss. Abstr. Int. 1987, 47, 3361-B; Chem. Abstr. 106, 156709. (d) Paquette, L. A.; Pansegrau, P. D.; Wiedeman, P. E.; Springer, J. P. J. Org. Chem. 1988, 53, 1461 and references cited therein. (e) Boeckman R. K., Jr.; Springer, D. M.; Alessi, T. R. J. Am. Chem. Soc. 1989, 111, 8284.
5. For previous studies concerning the total synthesis of pleuromutilin, see: (a) Kahn, M. Tetrahedron Lett. 1980, 21, 4547. (b) Gibbons, E. G. J. Am. Chem. Soc. 1982, 104, 1767 and references cited therein. (c) Patten, A. H.; Trost, B. M. Diss. Abstr. Int. 1987, 47, 3361-B; Chem. Abstr. 106, 156709. (d) Paquette, L. A.; Pansegrau, P. D.; Wiedeman, P. E.; Springer, J. P. J. Org. Chem. 1988, 53, 1461 and references cited therein. (e) Boeckman R. K., Jr.; Springer, D. M.; Alessi, T. R. J. Am. Chem. Soc. 1989, 111, 8284.
6. For previous studies concerning the total synthesis of pleuromutilin, see: (a) Kahn, M. Tetrahedron Lett. 1980, 21, 4547. (b) Gibbons, E. G. J. Am. Chem. Soc. 1982, 104, 1767 and references cited therein. (c) Patten, A. H.; Trost, B. M. Diss. Abstr. Int. 1987, 47, 3361-B; Chem. Abstr. 106, 156709. (d) Paquette, L. A.; Pansegrau, P. D.; Wiedeman, P. E.; Springer, J. P. J. Org. Chem. 1988, 53, 1461 and references cited therein. (e) Boeckman R. K., Jr.; Springer, D. M.; Alessi, T. R. J. Am. Chem. Soc. 1989, 111, 8284.
7. For previous studies concerning the total synthesis of pleuromutilin, see: (a) Kahn, M. Tetrahedron Lett. 1980, 21, 4547. (b) Gibbons, E. G. J. Am. Chem. Soc. 1982, 104, 1767 and references cited therein. (c) Patten, A. H.; Trost, B. M. Diss. Abstr. Int. 1987, 47, 3361-B; Chem. Abstr. 106, 156709. (d) Paquette, L. A.; Pansegrau, P. D.; Wiedeman, P. E.; Springer, J. P. J. Org. Chem. 1988, 53, 1461 and references cited therein. (e) Boeckman R. K., Jr.; Springer, D. M.; Alessi, T. R. J. Am. Chem. Soc. 1989, 111, 8284.
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10. No selectivity in the reduction was observed with Pd/C; reduction with diimide was selective but the yield was poor.
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12. ACCN: 1,1′-azobis(cyclohexanecarbonitrile). CAS registry number: 2094-98-6.
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15. For reviews on the chemistry of xanthates, see: (a) Zard, S. Z. Angew. Chem., Int. Ed. Engl. 1997, 36, 672. (b) Quiclet-Sire, B.; Zard, S. Z. Phosph. Sulf. Silicon 1999, 153-154, 137. (c) Zard, S. Z. Radical in Organic Synthesis, 1st ed.; Renaud, P., Sibi, M., Eds.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2001, p 90. For other examples of 8-endotrig radical cyclizations mediated by a xanthates, see: (d) Udding, J. H.; Giesselink, J. P. M.; Hiemstra, H.; Speckamp, W. N. J. Org. Chem. 1994, 59, 6671
16. For reviews on the chemistry of xanthates, see: (a) Zard, S. Z. Angew. Chem., Int. Ed. Engl. 1997, 36, 672. (b) Quiclet-Sire, B.; Zard, S. Z. Phosph. Sulf. Silicon 1999, 153-154, 137. (c) Zard, S. Z. Radical in Organic Synthesis, 1st ed.; Renaud, P., Sibi, M., Eds.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2001, p 90. For other examples of 8-endotrig radical cyclizations mediated by a xanthates, see: (d) Udding, J. H.; Giesselink, J. P. M.; Hiemstra, H.; Speckamp, W. N. J. Org. Chem. 1994, 59, 6671
17. For reviews on the chemistry of xanthates, see: (a) Zard, S. Z. Angew. Chem., Int. Ed. Engl. 1997, 36, 672. (b) Quiclet-Sire, B.; Zard, S. Z. Phosph. Sulf. Silicon 1999, 153-154, 137. (c) Zard, S. Z. Radical in Organic Synthesis, 1st ed.; Renaud, P., Sibi, M., Eds.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2001, p 90. For other examples of 8-endotrig radical cyclizations mediated by a xanthates, see: (d) Udding, J. H.; Giesselink, J. P. M.; Hiemstra, H.; Speckamp, W. N. J. Org. Chem. 1994, 59, 6671
18. For reviews on the chemistry of xanthates, see: (a) Zard, S. Z. Angew. Chem., Int. Ed. Engl. 1997, 36, 672. (b) Quiclet-Sire, B.; Zard, S. Z. Phosph. Sulf. Silicon 1999, 153-154, 137. (c) Zard, S. Z. Radical in Organic Synthesis, 1st ed.; Renaud, P., Sibi, M., Eds.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2001, p 90. For other examples of 8-endotrig radical cyclizations mediated by a xanthates, see: (d) Udding, J. H.; Giesselink, J. P. M.; Hiemstra, H.; Speckamp, W. N. J. Org. Chem. 1994, 59, 6671
19. Interestingly, we have used xanthates to perform radical additions directly onto the vinyl group at C-12 of Pleuromutilin itself, without prior protection of any of the functional groups. See: Bacqué, E.; Pautrat, F. ; Zard, S. Z. Chem. Commun. 2002, 2312.