Total synthesis of (+)-chaetocin and its analogues: their histone methyltransferase G9a inhibitory activity.
The first total synthesis of (+)-chaetocin has been accomplished in nine steps starting from known N-Cbz-N-Me-serine using radical alpha-bromination reaction of diketopiperazine 10 and Co(I)-mediated reductive dimerization reaction of 12 as key reactions. The enantiomers show comparable inhibitory activity toward histone methyltransferase (HMT) G9a, but analogues without the sulfur functionality are inactive.
Iwasa
Eriko
E
RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Hamashima
Yoshitaka
Y
Fujishiro
Shinya
S
Higuchi
Eisuke
E
Ito
Akihiro
A
Yoshida
Minoru
M
Sodeoka
Mikiko
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D010879:Piperazines; C002511:chaetocin; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase