ABSTRACT
The highly pyramidalized alkene, pentacyclo[4.3.0.0(2,4).0(3,8).0(5,7)]non-4-ene (9), has been generated via treatment of 4,5-diiodopentacyclo[4.3.0.0(2,4).0(3,8).0(5,7)]nonane (12) with n-butyllithium and tert-butyllithium. The title alkene has also been trapped as its Diels-Alder adduct with 1,3-diphenylisobenzofuran, 2,5-dimethylfuran, and spiro[2.4]hepta-4,6-diene. Products resulting from alkyllithium addition to the pyramidalized double bond of 9 have been isolated and fully characterized spectroscopically. The geometry, olefin strain energy, heat of hydrogenation, and relative HOMO/LUMO energies of 9 have been obtained by ab initio calculations at the MP2 and B3LYP levels using the 6-31G* basis set.
Subject(s)
Alkenes/chemistry , Alkenes/chemical synthesis , Heterocyclic Compounds/chemistry , Organometallic Compounds/chemistry , Heterocyclic Compounds/chemical synthesis , Isomerism , Models, Chemical , Models, Molecular , Molecular Structure , ThermodynamicsABSTRACT
We describe the development of cell-permeable beta-secretase inhibitors that demonstratively inhibit the production of the secreted amino terminal fragment of an artificial amyloid precursor protein in cell culture. In addition to potent inhibition in a cell-based assay (IC50 < 100 nM), these inhibitors display impressive selectivity against other biologically relevant aspartyl proteases.