Atropisomeric Properties of the Dibenzo[b,d]azepin-6-one Nucleus

Abstract

Dibenzo[b,d]azepin-6-ones (2a,b) were separated by chiral HPLC into the aR- and aS-atropisomers with high stereochemical stability, and methylation at C7 of 2a stereoselectively gave the (aR*,7R*) isomer (4a), which converted to the thermodynamically stable (aS*,7R*) atropisomer (5a) after heating.

Synthesis and axial chirality of an enantiopure aminodibenzazepinone

“…The findings are illustrated in Figure 2 and indicate that the barrier for rotation about the biaryl bond 10 to be 22.34 kcal/mol, which is in good agreement 11 with the recently found value of 23.4 kcal/mol. 3 The discrepancy may point toward some solvent effect, as Natsugari's results were obtained in toluene, and ours in i-PrOH/heptane. While we were not surprised that the rotational barrier for the system was low, an explanation for the chiral stability of amine 7 was still lacking.…”

“…The cell volume of crystal structure was 1526.79(4) Å. 3 The calculated density of the structure is 1.398 g/ cm 3 at 100 K. The structure was solved by direct methods. 16 All atomic parameters were independently refined.…”

Atropisomerie als Herausforderung in der Medikamentenentwicklung

“…Das Vorliegen von Atropisomerie ist nicht immer sofort offensichtlich: Während BMS-207940 (11) [15] und LY-411575 (12) [16] gehinderte Biaryle sind, die sich nicht überraschend unter bestimmten Bedingungen atropisomer verhalten, fallen ähnliche Strukturmotive bei dem Chinoxalindion 13, [17] dem HIV-Integrase-Inhibitor 14 [18] und dem Bcl-2-Liganden 15 [19] nicht sofort ins Auge (Schema 7). Neben Biarylen werden auch gehinderte Arylamide häufig dadurch charakterisiert, dass sich ihre Konformere langsam ineinander umwandeln.…”

The Application of Molecular Tethers in Controlling Axial Chirality

“…[1] Axially chiral structures are also found in nature and often possess interesting biological properties. [2][3][4][5] Atropisomers of the same natural product may display radically different activities. [6][7][8] For example, the dibenzocyclooctadiene steganacin (1) was found to be an especially potent antitumor agent with significant in vivo activity against P388 leukaemia cells and in vitro activity against human throat cancer cells (Figure 2).…”