Synthesis and antimalarial activity of novel medium-sized 1,2,4,5-tetraoxacycloalkanes.
CsOH- or Ag(2)O-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.
Kim
H S
HS
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.
Nagai
Y
Y
Ono
K
K
Begum
K
K
Wataya
Y
Y
Hamada
Y
Y
Tsuchiya
K
K
Masuyama
A
A
Nojima
M
M
McCullough
K J
KJ
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002586:Cesium; D003500:Cyclization; D004353:Drug Evaluation, Preclinical; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006878:Hydroxides; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D010087:Oxides; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D018030:Silver Compounds; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
C430901:1,2,6,7-tetraoxaspiro(7.11)nonadecane; D000962:Antimalarials; D006574:Heterocyclic Compounds, 2-Ring; D006878:Hydroxides; D010087:Oxides; D018030:Silver Compounds; D013141:Spiro Compounds; D002586:Cesium; C040225:disilver oxide