ABSTRACT
Quassinoids are highly oxygenated triterpenes, which were isolated as bitter principles from the plants of Simaroubaceae family. Their synthesis has attracted much attention because of the wide spectrum of their biological properties. The most prevalent quassinoids have C-20 picrasane skeleton, some known as bruceolides as they were isolated from the genus Brucea, which showed marked antileukemic and antimalarial activities.
Subject(s)
Drug Design , Plants, Medicinal/chemistry , Quassins , Animals , Antimalarials/chemistry , Antimalarials/isolation & purification , Antimalarials/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Brucea/chemistry , Quantitative Structure-Activity Relationship , Quassins/chemistry , Quassins/isolation & purification , Quassins/pharmacology , Triterpenes/chemistry , Triterpenes/isolation & purification , Triterpenes/pharmacologyABSTRACT
Bruceantin (1), a classical quassinoid with the highest reported antimalarial activity among the quassinoids examined thus far, was selected as a natural product lead for the design of a series of A/B-ring analogs. A viable strategy for the synthesis of the series was developed. The functionalized A-ring and the C-15 ester moiety in bruceantin are incorporated in all designed compounds. The preliminary bioassay results will be discussed in detail.
Subject(s)
Antimalarials/chemistry , Antimalarials/pharmacology , Drug Design , Quassins/chemistry , Quassins/pharmacology , Animals , Antimalarials/chemical synthesis , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Parasitic Sensitivity Tests , Plasmodium falciparum/drug effects , Quassins/chemical synthesis , Structure-Activity RelationshipABSTRACT
Regiospecific synthesis of 2,3-disubstituted-L-histidines and 2,3-disubstituted histamines starting from L-histidine methyl ester and histamine is reported. The key step involves homolytic free radical alkylation via silver catalyzed oxidative decarboxylation of alkylcarboxylic acids with ammonium persulfate.
