10.1021/ja981928i.s002 Dale L. Boger Dale L. Boger Susumu Miyazaki Susumu Miyazaki Olivier Loiseleur Olivier Loiseleur Richard T. Beresis Richard T. Beresis Steven L. Castle Steven L. Castle Jason H. Wu Jason H. Wu Qing Jin Qing Jin Thermal Atropisomerism of Aglucovancomycin Derivatives:  Preparation of (<i>M</i>,<i>M</i>,<i>M</i>)- and (<i>P</i>,<i>M</i>,<i>M</i>)-Aglucovancomycins American Chemical Society 1998 chain succinimide formation aldol ring cleavage Asn residue DE ring system atropisomers carboxamide protection CD ring system AB stereochemistries DE ring system aglucovancomycin derivatives DE ring system P DE atropisomer alcohol protection DE ring systems Thermal Atropisomerism antimicrobial activity 1998-08-22 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Thermal_Atropisomerism_of_Aglucovancomycin_Derivatives_Preparation_of_i_M_i_i_M_i_i_M_i_-_and_i_P_i_i_M_i_i_M_i_-Aglucovancomycins/3671355 The 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, (<i>M</i>,<i>M</i>,<i>M</i>)-<b>2</b>, and its unnatural DE atropisomer (<i>P</i>,<i>M</i>,<i>M</i>)-<b>2</b> from <b>6</b> are described. The comparative antimicrobial activity of the key derivatives and their unnatural DE ring system <i>P</i>-diastereomers are disclosed.