ABSTRACT
We have developed a new method for synthesizing chiral isotwistane and homoisotwistane skeletons as well as aminocyclitols in a highly stereoselective manner. These results were achieved through the use of a common intermediate, which was derived from the ytterbium-catalyzed asymmetric Diels-Alder reaction of Danishefsky diene.
Subject(s)
Alkanes/chemical synthesis , Bridged-Ring Compounds/chemical synthesis , Cyclitols/chemical synthesis , Cyclohexenes/chemistry , Alkanes/chemistry , Bridged-Ring Compounds/chemistry , Catalysis , Cyclitols/chemistry , Cycloaddition Reaction , Molecular Structure , Stereoisomerism , Ytterbium/chemistryABSTRACT
Inhibition of amyloid-ß (Aß) aggregation could be a drug development target for treating Alzheimer disease. Insufficient activity to inhibit aggregation, however, remains a key issue. Here, we report a covalent modifier-type aggregation inhibitor of Aß, diazirine-equipped cyclo-KLVF(ß-Ph)F (2). Due to the affinity of the cyclo-KLVFF motif for Aß, 2 selectively reacted with Aß1-42 under UV-light irradiation to form an irreversible covalent bond. The Tyr-10 residue of Aß1-42 was identified as the covalent modification site with 2. The extent of cross-ß-sheet structure, characteristics of amyloid aggregation, and toxicity of Aß1-42 were strongly attenuated by this chemical modification.
