ABSTRACT
In the tricyclic title compound, C11H12N2OS, the 2,3,4,5-tetra-hydro-pyridine ring adopts a half-chair conformation. This ring makes dihedral angles of 27.72â (7) and 45.17â (7)°, respectively, with the isoxazole and the cyclo-hexa-1,3-diene rings while the isoxazole ring is oriented at an acute angle of 63.46â (7)° with respect to the cyclo-hexa-1,3-diene ring. In the crystal, mol-ecules associate via C-Hâ¯N hydrogen bonds and C-Hâ¯π inter-actions, forming a three-dimensional network.
ABSTRACT
The natural product dodoneine (a dihydropyranone phenolic compound), extracted from African mistletoe Agelanthus dodoneifolius, has been investigated as inhibitor of several human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms. By using superacid chemistry, analogues of the lactone phenolic hybrid lead compound have been synthesized and tested as CA inhibitors. Small chemical modifications of the basic scaffold revealed strong changes in the selectivity profile against different CA isoforms. These new compounds selectively inhibited isoforms CA I (K(I)s in the range of 0.13-0.76 µM), III (K(I)s in the range of 5.13-10.80 µM), XIII (K(I)s in the range of 0.34-0.96 µM) and XIV (K(I)s in the range of 2.44-7.24 µM), and can be considered as new leads, probably acting as non-zinc-binders, similar to other phenols/lactones investigated earlier.
Subject(s)
Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrases/metabolism , Loranthaceae/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Humans , Phenols/chemistry , Phenols/isolation & purification , Phenols/pharmacology , Plant Extracts/isolation & purification , Protein Isoforms/metabolismABSTRACT
Detailed investigations on one of the key steps of the superacidic fluorination of Vinca alkaloids that is the origin of C20' activation are reported. While two different pathways can be envisioned for the emergence of the transient secondary carbocationic intermediate, isotopic labeling experiments unambiguously revealed the involvement of a 1,2-hydride shift mechanism.
Subject(s)
Vinca Alkaloids/chemistry , Acids/chemistry , Dimerization , Halogenation , Hydrogen-Ion Concentration , Molecular StructureABSTRACT
A new dihydropyranone, ( R)-6-[( S)-2-hydroxy-4-(4-hydroxyphenyl)butyl]-5,6-dihydropyran-2-one ( 1), was isolated from Tapinanthus dodoneifolius. The structure was determined from spectroscopic and X-ray crystallographic analysis. Compound 1 (named dodoneine) showed a relaxing effect on preconstricted rat aortic rings (IC 50 of 81.4 +/- 0.9 microM).
