ABSTRACT
Various derivatives of reveromycin A, an inhibitor of eukaryotic cell growth, and spirofungin A, focusing on the 5S hydroxyl group and C18 hemisuccinyl group, were synthesized and their inhibitory effects on both the isoleucyl-tRNA synthetase activity and the survival of osteoclasts, and activities on the morphological reversion of src(ts)-NRK cells were examined. It was found that 2,3-dihydroreveromycin A is the promising derivative of reveromycin A based on the activity and stability.
Subject(s)
Anti-Bacterial Agents/chemistry , Osteoclasts/metabolism , Pyrans/chemical synthesis , Spiro Compounds/chemical synthesis , Animals , Cell Cycle , Chemistry, Pharmaceutical/methods , Inhibitory Concentration 50 , Isoleucine-tRNA Ligase/chemistry , Kidney/cytology , Microbial Sensitivity Tests , Models, Chemical , Pyrans/chemistry , Rats , Spiro Compounds/chemistry , Streptomyces/metabolism , Succinates/chemistryABSTRACT
[chemical reaction: see text]. The stereocontrolled total synthesis of (-)-spirofungin A (1) and (+)-spirofungin B (2a), polyketide-type antibiotics having various antifungal activities, has been achieved employing the Weinreb amide 8, the alkyne 9, and the vinyl boronate 5 readily available from the common intermediate 10. The first synthesis proceeded with a longest linear sequence of 31 steps, affording (-)-1 and (+)-2a in 7.9% and 5.2% overall yields, respectively.
Subject(s)
Antifungal Agents/chemical synthesis , Pyrans/chemical synthesis , Spiro Compounds/chemical synthesis , Antifungal Agents/chemistry , Catalysis , Cyclization , Molecular Structure , Pyrans/chemistry , Spiro Compounds/chemistry , Stereoisomerism , Streptomyces/chemistryABSTRACT
A familial amyotrophic lateral sclerosis (FALS) patient with G37R mutation of superoxide dismutase 1 (SOD1) gene revealed an early onset and relatively slow progression. Neuropathological examination of this patient showed widespread neuronal degeneration extending to overall length of the spinal cord and the brainstem with extremely rare Lewy body-like inclusions (LBI), while there were no vacuoles in neurons, a characteristic feature in transgenic mice expressing G37R SOD1 mutation.
