RESUMO
Mitochonic acid-5 ameliorates the pathophysiology of human mitochondrial-disease fibroblasts and Caenorhabditis elegans Duchenne muscular dystrophy and Parkinson's disease models. Here, we found that 10 µM MA-5 attenuates the age-related decline in motor performance, loss of muscle mitochondria, and degeneration of dopaminergic neurons associated with mitochondrial Ca2+ overload in C. elegans. These findings suggest that MA-5 may act as an anti-aging agent against a wide range of neuromuscular dysfunctions in metazoans.
RESUMO
Convergent and scalable synthesis of the ABCDE-ring fragment of Caribbean ciguatoxin C-CTX-1, the major causative toxin for ciguatera poisoning in the Caribbean Sea and the Northeast Atlantic areas, is described in detail. The key features of the synthesis include an iterative use of 2,2,6,6-tetramethyl piperidine 1-oxyl (TEMPO)/PhI(OAc)2-mediated oxidative lactonization and Suzuki-Miyaura coupling en route to the DE-ring system and a convergent fragment coupling to form the ABCDE-ring skeleton via the Suzuki-Miyaura coupling strategy.