Synthesis and in vitro antimalarial activity of sulfone endoperoxides.
A series of 4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]+ ++nonanes, carrying a variety of substituents at position-8 (4) were prepared by a short and efficient method from R-(+)-limonene. Key reactions include thiol oxygen cooxidation, and alkylation and acylation of a sterically hindered tertiary alcohol compatible with the endoperoxy functionality. Some of compounds 4, which are structurally related to yingzhaosu A (2), were found to exhibit in vitro antimalarial activity comparable to that of artemisinin (1) and superior to that of arteflene (3).
Bachi
M D
MD
Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Korshin
E E
EE
Ploypradith
P
P
Cumming
J N
JN
Xie
S
S
Shapiro
T A
TA
Posner
G H
GH
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004365:Drugs, Chinese Herbal; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010545:Peroxides; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000737:chemistry; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000962:Antimalarials; D004365:Drugs, Chinese Herbal; D010545:Peroxides; D012717:Sesquiterpenes; D013450:Sulfones; D002738:Chloroquine