Solid-phase synthesis and biological activity of malformin C and its derivatives.
We accomplished the solid-phase total synthesis of malformin C, which is adaptable for the easy preparation of various derivatives. A solid-phase total synthesis of malformin C was achieved by on-resin macrolactamization and disulfide bond formation, with concurrent cleavage from the resin. Antimalarial and antitrypanosomal activities were examined, which helped elucidate partial structure-activity relationships. Results indicate that the disulfide bond is essential and branched amino acids are also crucial components if the compound is to exhibit potent antimalarial and antitrypanosomal properties.
Kojima
Yasuhiro
Y
Kitasato Institute, Kitasato Institute for Life Science and Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
Sunazuka
Toshiaki
T
Nagai
Kenichiro
K
Hirose
Tomoyasu
T
Namatame
Miyuki
M
Ishiyama
Aki
A
Otoguro
Kazuhiko
K
Omura
Satoshi
S
D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D010456:Peptides, Cyclic; C001675:malformins