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Synthesis of 1,2,4-trioxepanes via application of thiol-olefin co-oxygenation methodology.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2006 Dec 01; Vol. 16 (23), pp. 6124-30. Date of Electronic Publication: 2006 Sep 15. - Publication Year :
- 2006
-
Abstract
- Thiol-olefin co-oxygenation (TOCO) of substituted allylic alcohols generates beta-hydroxy peroxides that can be condensed in situ with various ketones, to afford a series of functionalised 1,2,4-trioxepanes in good yields. Manipulation of the phenylsulfenyl group in 8a-8c allows for convenient modification to the spiro-trioxepane substituents. Surprisingly, and in contrast to the 1,2,4-trioxanes examined, 1,2,4-trioxepanes are inactive as antimalarials up to 1000 nM and we rationalize this observation based on the inherent stability of these systems to ferrous mediated degradation. FMO calculations clearly show that the sigma* orbital of the peroxide moiety of 1,2,4-trioxane derivatives 4a and 14b are lower in energy and more accessible to attack by Fe(II) compared to their trioxepane analogues 8b and 9b.
- Subjects :
- Animals
Antimalarials chemistry
Iron chemistry
Models, Molecular
Molecular Structure
Oxepins chemical synthesis
Oxepins pharmacology
Plasmodium falciparum drug effects
Structure-Activity Relationship
Alkenes chemistry
Antimalarials chemical synthesis
Antimalarials pharmacology
Oxepins chemistry
Oxygen chemistry
Sulfhydryl Compounds chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0960-894X
- Volume :
- 16
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 16978862
- Full Text :
- https://doi.org/10.1016/j.bmcl.2006.08.098