A. Jossang et al., 2 HIGHLY POPULATED CONFORMATIONS AT ROOM-TEMPERATURE OF MONTERINE ANDGRANJINE, ANTITUMOR BISBENZYLISOQUINOLINE ALKALOIDS - ORIGIN AND TRIDIMENSIONAL STRUCTURES, Journal of organic chemistry, 61(9), 1996, pp. 3023-3030
Monterine 1 as well as granjine 3, 1R,1'S configured biphenylic bisben
zylisoquinoline alkaloids, generate two highly populated conformers. T
he interconversion of two forms was detected by saturation tranfer in
H-1 NMR NOEs experiments. Tridimensional structure of the conformers w
as determined on the basis of 1H NMR analysis of anisotropic shielding
protons, by NOEs measurements and vicinal proton coupling constants o
f CH1-CH2 alpha and CH1'-CH2 alpha'. The structures established from N
MR data were further refined to observe the mobility of 3D conformatio
ns by molecular dynamics simulation in vacuo. The highly populated con
formers, monterine 1a and 1b, as well as granjine 3a and 3b, are inter
convertible by rotation about the C1'-C alpha', C alpha'-C9', and C11'
-C11 bonds and inversion of the benzyl D ring by reference to CH2 alph
a'. The slow exchange system was investigated by dynamic NMR spectrosc
opy: Delta G(c)(double dagger) 77.9 KJ/mol and k(c) 200 s(-1) for mont
erine 1; Delta G(c)(double dagger) 77.7 KJ/mol and k(c) 211 s(-1) for
granjine 3. Natural and synthetic biphenylic bisbenzylisoquinolines di
splayed, in vitro, cytotoxic activities against human prostate and bre
ast cancer cell lines.