Synthesis of new 6-alkylvinyl/arylalkylvinyl substituted 1,2,4-trioxanes active against multidrug-resistant malaria in mice.
3-Alkyl/arylalkyl substituted 2-butenols 9, 10, 23a-d undergo regiospecific photooxygenation to furnish beta-hydroxyhydroperoxides 11, 12, 24a-d, respectively, in reasonable yields. Acid catalyzed condensation of 11, 12, 24a-d with various ketones furnish new 1,2,4-trioxanes 13-18, 25a-d, 26a-d, 27a-d in good yields. Several of these trioxanes show promising antimalarial activity against multidrug-resistant Plasmodium yoelii in mice by oral and intramuscular routes.
Singh
Chandan
C
Division of Medicinal & Process Chemistry, Central Drug Research Institute, Lucknow 226001, India. chandancdri@yahoo.com
Gupta
Nitin
N
Puri
Sunil K
SK
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000502:physiology; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000502:physiology; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use
D000962:Antimalarials; D012717:Sesquiterpenes