Covalent Tethering and Residues with Bulky Hydrophobic Side Chains Enable Self-Assembly of Distinct Amyloid Structures.

Polymorphism is a common property of amyloid fibers that complicates their detailed structural and functional studies. Here we report experiments illustrating the chemical principles that enable the formation of amyloid polymorphs with distinct stoichiometric composition. Using appropriate covalent tethering we programmed self-assembly of a model peptide corresponding to the [20-41] fragment of human β2-microglobulin into fibers with either trimeric or dimeric amyloid cores.

Chiral recognition in amyloid fiber growth.

Insoluble amyloid fibers represent a pathological signature of many human diseases. To treat such diseases, inhibition of amyloid formation has been proposed as a possible therapeutic strategy. d-Peptides, which possess high proteolytic stability and lessened immunogenicity, are attractive candidates in this context.

Antimalarial bicyclic peroxides belonging to the G-factor family: mechanistic aspects of their formation and iron (II) induced reduction.

Artemisinin and its derivatives are peroxide-containing compounds targeting P. falciparum. We review here structural analogues of bicyclic peroxides belonging to the G factors family presenting antimalarial properties.

Design, synthesis and evaluation of new tricyclic endoperoxides as potential antiplasmodial agents.

Diastereoselective autoxidation allowed preparation of new tricyclic endoperoxides. These compounds and their methylated analogs were evaluated against the in vitro growth of Plasmodium falciparum, the malaria-causing parasite, showing moderate activities. However, hybrid molecules composed of the tricyclic peroxide moiety and 7-chloro-4-aminoquinoline were synthesized and displayed a marked increase in antiplasmodial activity.

Concise enantioselective total syntheses of (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine and (+)-norchelidonine by a Pd II-catalyzed ring-opening strategy.

New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine, and (+)-norchelidonine are described. Our rapid and convergent route to this class of natural products involved the development and application of a Pd II-catalyzed asymmetric ring-opening reaction of a meso-azabicyclic alkene with an aryl boronic acid as the key step. By screening a variety of functionalized ortho-substituted aryl boronic acids, chiral ligands and reaction conditions we were able to prepare the requisite cis-1-amino-2-aryldihydronaphthalenes in high yield and in up to 90 % ee.