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An efficient route for the preparation of a 21-fluoro progestin-16 alpha,17 alpha-dioxolane, a high-affinity ligand for PET imaging of the progesterone receptor.
- Source :
-
The Journal of organic chemistry [J Org Chem] 2002 Jul 12; Vol. 67 (14), pp. 4904-10. - Publication Year :
- 2002
-
Abstract
- Two different synthetic routes were explored for the synthesis of fluoro furanyl norprogesterone (FFNP) 1, a high-affinity ligand for the progesterone receptor (PgR) that is being developed as a PET imaging agent for PgR-positive breast cancer. Both approaches proceed through a key intermediate, triol 5. The first approach, starting from keto-ketal 2, employed a dioxenyl group as a synthon for installing a corticosteroid side chain in keto-alcohol 4. The second approach, starting from propargylic acetate 12b, involved the application of a two-step method, a Pd(II)-catalyzed oxidative rearrangement followed by a base-catalyzed acetate rearrangement of the intermediate unsaturated acetate 13b, to generate the requisite corticosteroid side chain in keto-acetate 14b. This intermediate was further elaborated to the final product 1 via efficient dihydroxylation with potassium permangnate, furan acetalization with scandium triflate, and mesylation and fluorination reactions. The palladium-catalyzed route is considerably more efficient than the dioxene approach for the synthesis of key intermediate triol 5, and the scandium triflate-catalyzed acetalization, in particular, led to a considerable improvement in the overall yield of the endo furan acetal alcohol 16a. This route provides a major improvement in the overall yield of the final progestin target, FFNP 1.
- Subjects :
- Catalysis
Female
Humans
Ligands
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Oxidation-Reduction
Palladium chemistry
Stereoisomerism
Tomography, Emission-Computed methods
Breast Neoplasms diagnostic imaging
Chemistry, Organic methods
Fluorine Radioisotopes
Norpregnenes chemical synthesis
Receptors, Progesterone metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3263
- Volume :
- 67
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- The Journal of organic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12098304
- Full Text :
- https://doi.org/10.1021/jo020190r