Enantioselective syntheses and biological studies of aeruginosin 298-A and its analogs: application of catalytic asymmetric phase-transfer reaction.
Aeruginosin 298-A was isolated from the freshwater cyanobacterium Microcystis aeruginosa (NIES-298) and is an equipotent thrombin and trypsin inhibitor. A variety of analogs were synthesized to gain insight into the structure-activity relations. We developed a versatile synthetic process for aeruginosin 298-A as well as several attractive analogs, in which all stereocenters were controlled by catalytic asymmetric phase-transfer reaction promoted by two-center asymmetric catalysts and catalytic asymmetric epoxidation promoted by a lanthanide-BINOL complex. Furthermore, serine protease inhibitory activities of aeruginosin 298-A and its analogs were examined.
Fukuta
Yuhei
Y
Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Ohshima
Takashi
T
Gnanadesikan
Vijay
V
Shibuguchi
Tomoyuki
T
Nemoto
Tetsuhiro
T
Kisugi
Takaya
T
Okino
Tatsufumi
T
Shibasaki
Masakatsu
M
D000478:Alkylation; D002384:Catalysis; D004852:Epoxy Compounds / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009284:Naphthols / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014361:Trypsin Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
C406944:BINOL, naphthol; D004852:Epoxy Compounds; D009284:Naphthols; D014361:Trypsin Inhibitors; C419325:aeruginosin 298-A; D007930:Leucine