ABSTRACT
A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells. Using an efficient synthetic route, the agricultural and medicinal activity was explored.
Subject(s)
Antineoplastic Agents/pharmacology , Fungicides, Industrial/pharmacology , Pyrazines/pharmacology , Tubulin Modulators/chemistry , Tubulin Modulators/pharmacology , Tubulin/metabolism , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Fungicides, Industrial/chemistry , Humans , Microbial Sensitivity Tests , Molecular Structure , Pyrazines/chemistry , Structure-Activity RelationshipABSTRACT
An enantioselective synthesis of (+)-coronafacic acid has been achieved. Rhodium-catalyzed cyclization of an alpha-diazoester provided the intermediate cyclopentanone in high enantiomeric purity. Subsequent Fe-mediated cyclocarbonylation of a derived alkenyl cyclopropane gave a bicyclic enone that then was hydrogenated and carried on to the natural product.
Subject(s)
Indenes/chemical synthesis , Biological Products/chemical synthesis , Catalysis , Cyclization , Cyclopentanes , Hydrogenation , Rhodium , StereoisomerismABSTRACT
2-Alkyl cyclohexenones are useful intermediates for organic synthesis. The Wittig reaction of a series of aldehydes with (cyclopropylmethyl)triphenylphosphonium bromide delivered the corresponding alkenyl cyclopropanes. UV irradiation in the presence of Fe(CO)5 converted the alkenyl cyclopropanes to the 2-substituted cyclohexenones. This approach enabled a three-step synthesis of the tricyclic core of estrone methyl ether.
Subject(s)
Steroids/chemical synthesis , Aldehydes/chemistry , Catalysis , Cyclization , Cyclopropanes/chemistry , Iron Compounds/chemistry , Ketones/chemistry , Steroids/chemistryABSTRACT
[reaction: see text] The TiCl4-mediated reaction of an ester with benzoyl chloride results in high yields of the alpha-benzoylated ester. Diazo transfer of the benzoylated ester utilizing p-acetoamidobenzenesulfonyl azide affords the alpha-diazo ester in good yield. Using this simplified procedure, it is easy to prepare gram quantities of alpha-diazo esters.
