ja981928i_si_002.pdf (777.16 kB)
Thermal Atropisomerism of Aglucovancomycin Derivatives: Preparation of (M,M,M)- and (P,M,M)-Aglucovancomycins
journal contribution
posted on 1998-08-22, 00:00 authored by Dale L. Boger, Susumu Miyazaki, Olivier Loiseleur, Richard T. Beresis, Steven L. Castle, Jason H. Wu, Qing JinThe degradation of vancomycin to a series of aglucovancomycin derivatives containing modifications
in key functional groups and a study of their thermal atropisomerism are detailed. In all of the cases, selective
isomerism of the DE ring system atropisomers was observed under conditions where the CD and AB
stereochemistries were unaffected. Competitive retro aldol ring cleavage of the CD and DE ring systems (CD
> DE) was observed but could be minimized by the choice of solvent and thermal conditions (DE ring system)
or precluded by alcohol protection (CD ring system). Similarly, competitive main chain succinimide formation
through the loss of ammonia from the Asn residue could be minimized by the choice of thermal conditions or
prevented by carboxamide protection. Resynthesis of natural aglucovancomycin, (M,M,M)-2, and its unnatural
DE atropisomer (P,M,M)-2 from 6 are described. The comparative antimicrobial activity of the key derivatives
and their unnatural DE ring system P-diastereomers are disclosed.