Absolute configuration of stegane lignans by vibrational circular dichroism

Novel steganes (−)-(P,8R,8′R)-5′-desmethoxystegane 4, (−)-(P,7R,8R,8′R)-5′-desmethoxysteganol 5, (−)-(P,7R,8R,8′R)-5′-desmethoxysteganacin 6, and (−)-(P,8R,8′R)-5′-desmethoxysteganone 7 were synthesized from (+)-(M,8R,8′R)-5′-desmethoxyisostegane 2, which in turn was obtained from natural (−)-(8R,8′R)-5′-desmethoxyyatein 1 together with the novel (+)-(M,8R,8′R)-3,4-dihydroxy-3′,4′-dimethoxyisosteganolide 3. Their stereostructures were determined by 1D and 2D NMR spectroscopy, while their absolute configuration was assigned by vibrational circular dichroism (VCD) measurements in combination with density functional theory calculations. Thus, the VCD spectrum of 2 was contrasted with that of its atropisomeric derivative 4 obtained by thermal inversion of the chiral axis. These compounds exhibited numerous opposite VCD transitions due to the predominance of the biaryl core, thus allowing the identification of bands arising from local (8R,8′R) and non-local (M/P) chirality. The conformational analysis of these compounds revealed that the eight-membered ring of 2 adopts a single twist-boat–chair conformation, while in 4 it exists in an equilibrium between two different twist-boat conformations. The introduction of an acetyl group at C-7 in 4 to give 6 shifted the conformational equilibrium toward a single twist-boat conformation which was verified by VCD spectroscopy.

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(M,8R,8′R)-5′-DesmethoxyisosteganeC21H20O6100% ee[α]D20 = +145.0 (c 1.63, CH3OH)Source of chirality: (−)-5′-desmethoxyyateinAbsolute configuration: (M,8R,8′R)

(M,8R,8′R)-3,4-Dihydroxy-3′,4′-dimethoxyisosteganolideC20H20O6100% ee[α]D20 = +150.8 (c 1.0, CHCl3)Source of chirality: (−)-5′-desmethoxyyateinAbsolute configuration: (M,8R,8′R)

(P,8R,8′R)-5′-DesmethoxysteganeC21H20O6100% ee[α]D20 = −83.8 (c 0.24, CH3OH)Source of chirality: (−)-5′-desmethoxyyateinAbsolute configuration: (P,8R,8′R)

(P,7R,8R,8′R)-5′-DesmethoxysteganolC21H20O7100% ee[α]D20 = −141.7 (c 0.93, CHCl3)Source of chirality: (−)-5′-desmethoxyyateinAbsolute configuration: (P,7R,8R,8′R)

(P,7R,8R,8′R)-5′-DesmethoxysteganacinC23H22O8100% ee[α]D20 = −113.5 (c 1.1, CHCl3)Source of chirality: (−)-5′-desmethoxyyateinAbsolute configuration: (P,7R,8R,8′R)

(P,8R,8′R)-5′-DesmethoxysteganoneC21H18O7100% ee[α]D20 = −136.0 (c 0.35, CHCl3)Source of chirality: (−)-5′-desmethoxyyateinAbsolute configuration: (P,8R,8′R)