Synthesis and Antimalarial Activity of Novel Medium-Sized 1,2,4,5-Tetraoxacycloalkanes

• Published in: Journal of medicinal chemistry Vol. 44; no. 14; pp. 2357 - 2361
• Main Authors: Kim, Hye-Sook, Nagai, Yukiko, Ono, Kanako, Begum, Khurshida, Wataya, Yusuke, Hamada, Yoshiaki, Tsuchiya, Kaoru, Masuyama, Araki, Nojima, Masatomo, McCullough, Kevin J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 05-07-2001
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Antiparasitic agents; Biological and medical sciences; Cesium; Cyclization; Drug Evaluation, Preclinical; Heterocyclic Compounds, 2-Ring - chemical synthesis; Heterocyclic Compounds, 2-Ring - chemistry; Heterocyclic Compounds, 2-Ring - pharmacology; Hydroxides; Malaria - drug therapy; Malaria - parasitology; Medical sciences; Mice; Oxides; Pharmacology. Drug treatments; Plasmodium berghei; Plasmodium falciparum - drug effects; Silver Compounds; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Spiro Compounds - pharmacology; Structure-Activity Relationship; Antimalarial; Intraperitoneal administration; Oxygen heterocycle; Peracetal; Plasmodium falciparum; Plasmodium berghei; Structure activity relation; Parasiticid; Bicyclic compound; Chemical synthesis; Protozoa; Apicomplexa; Rodentia; Oral administration; Parasitosis; In vitro; Spiran; Infection; In vivo; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Mouse; Animal; Organic peroxide
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm010026g

CsOH- or Ag2O-mediated cycloalkylation of (alkylidene)bisperoxides 3 and 1,n-dihaloalkanes (n = 3−8) provided the corresponding medium-sized 1,2,4,5-tetraoxacycloalkanes 4−8 in moderate yields. Subsequent evaluation of the antimalarial activity of the cyclic peroxides 4−8 in vitro and in vivo revealed that 1,2,6,7-tetraoxaspiro[7.11]nonadecane 4a has considerable potential as a new, inexpensive, and potent antimalarial drug.