Email Discussion: Re: Poster 26 Donald Craig : Template-Directed Intramolecular Tom McCarthy
Email Discussion: Re: questions on poster 26 from Dr Tom McCarthy d.craig@ic.ac.uk

Template-Directed Intramolecular C-Glycosidation

Donald Craig,* Andrew H. Payne, Mark W. Pennington, Jason P. Tierney

Department of Chemistry, Imperial College of Science, Technology and Medicine

We have been developing strategies for the stereoselective synthesis of bicyclic and monocyclic C-glycosides by cationic cyclisation reactions. Thus, bicyclic ketooxetanes 2 and ketooxolanes 4 may be prepared by silver triflate-mediated closure of substrates 1 and 3.[1],2 We have successfully applied this chemistry to the enantioselective synthesis of the potent KDO inhibitor 2,3-deoxy-D-manno-2-octulopyranosate 5.[3]

We are now seeking to exploit this strategy to access stereochemically more complex bicyclo[4.4.0] systems, and to explore a range of derivatisation reactions of these materials. Thus, substrate 7 has been prepared, and we are looking at its silver (I)-induced cyclisation. Baeyer-Villiger (B-V) oxidation of the ring-closed product 11 is expected to yield acetals 10 and thence lactones 9. Subjection of 11 to reductive tether cleavage would give methyl ketones 12, from which carbinols 13 could be made by Baeyer-Villiger oxidation followed by hydrolysis. It is intended to apply these sequences to the synthesis of the antitumour agent goniofufurone 64 and the central sub-unit 8 of the antibiotic efrotomycin.[5]

The paper is presented as a collection of slides, click on the hyperlinks below to receive the pictures:

  1. Introduction
  2. Strategy
  3. Prototype substrates
  4. Sythesis of prototype substrates
  5. Cyclisation Reactions
  6. Cyclisation of a more substituted substrate
  7. Oxetanes are accessible using this strategy!
  8. Synthesis of 5-membered bicyclic C-glycosides
  9. The separate anomers of thioglycoside show different cyclisation selectivities
  10. Application to bioactive compound synthesis
  11. Retrosynthetic analysis of 2-deoxyKDO
  12. 2-DeoxyKDO synthesis: assembly of the pyran sigma-framework
  13. Pyran construction and adjustment of stereochemistry
  14. Glycal formation and attachment of a cinnamyl side-chain
  15. Cyclisation os the cinnamyl ether and elaboration of the dihydropyran
  16. Completion of the synthesis of 2-deoxyKDO
  17. Acknowledgements

References

[1] Craig, D.; Munasinghe, V. R. N. J. Chem. Soc., Chem. Commun. 1993, 901.

2 Craig, D.; Pennington, M. W.; Warner, P. Tetrahedron Lett. 1993, 34, 8539.

[3] Craig, D.; Pennington, M. W.; Warner, P., manuscript in preparation.

[4] See: Fang, X.-P.; Anderson, J. E.; Chang, C.-J.; Fanwick, P. E.; McLaughlin, J. L. J. Chem. Soc., Perkin Trans. 1, 1990, 1665.

[5] Dolle, R. E.; Nicolaou, K. C. J. Am. Chem. Soc. 1985, 107, 1691, 1695, and references therein.

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