The relationship between the CD Cotton effect and the absolute configuration of FD-838 and its seven stereoisomers.
Three new metabolites having a spiro-heterocyclic gamma-lactam core, cephalimysins B-D (1-3), as well as FD-838 (4) were isolated from a culture broth of Aspergillus fumigatus that was originally separated from the marine fish Mugil cephalus. Compounds 1-3 are the diastereomers of 4. Compounds 2 and 3 exhibit an opposite absolute configuration at a spiro carbon to that of other known naturally occurring spiro-heterocyclic gamma-lactams. In addition, we succeeded in the chemical transformation of the four natural products (1-4) into their epimers (1'-4') at C-8 to afford all the stereoisomers of FD-838 (4) with three stereogenic centers. Consequently, the relationship between the absolute configuration at stereogenic centers and the CD Cotton effects for these compounds could be unambiguously established. All of the compounds except 1 moderately inhibited the growth of cultured P388 and HL-60 cell lines.
Yamada
Takeshi
T
Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan. yamada@gly.oups.ac.jp
Kitada
Hiroki
H
Kajimoto
Tetsuya
T
Numata
Atsushi
A
Tanaka
Reiko
R
D000818:Animals; D001232:Aspergillus fumigatus / Q000737:chemistry*; D005663:Furans / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D023701:Smegmamorpha; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification*; D013237:Stereoisomerism
C529961:FD 838; D005663:Furans; D007093:Imidazoles; D007769:Lactams; D013141:Spiro Compounds; C552154:cephalimysin B; C552156:cephalimysin C; C552155:cephalimysin D