Thermal Atropisomerism of Teicoplanin Aglycon Derivatives: Preparation of the P,P,P and M,P,P Atropisomers of the Teicoplanin Aglycon via Selective Equilibration of the DE Ring System

The degradation of teicoplanin to a series of key aglycon derivatives, including those containing a cleaved FG ring system, and a study of their thermal atropisomerism are detailed. In all cases, selective equilibration of the DE ring system was observed to provide a 1:1 mixture of P:M atropisomers under conditions in which the AB and CD atropisomer stereochemistry were unaffected. The DE atropisomer equilibration was found to occur with an Ea of 29.3 and 24.8−25.2 kcal/mol for 6a (FG ring system intact) and 10/12 (cleaved FG ring system), respectively, which is comparable to that of a vancomycin aglycon DE ring system (Ea = 23.6 kcal/mol) and more facile than the CD (Ea = 30.4 kcal/mol) or O-methylated AB ring system (Ea = 37.8 kcal/mol). Consistent with intuitive expectations, the intact teicoplanin FG ring system slowed the rate of isomerization, contributing ca. 4.0 kcal/mol to the Ea (6a vs 10), and the bulky C23 substituent on teicoplanin acyclo FG derivatives had a much less significant effect, con...