Withasteroids ofPhysalis. VII. 14α-Hydroxyixocarpanolide and 24,25-expoxywithanolide D

Natural withanolides, an update

“…Compounds 1–43 (ref. 25–52) are 5β,6β-epoxy withanolides with a 2-en-1-one unit. X-ray diffraction studies of withanolide D ( 1 ), isolated from Withania sonznifer in 1968, 33 revealed the connections and conformations of rings A–E: rings A/B are cis connected, and rings B/C and C/D are trans connected.…”

“…Withanolides 20-28 contain a 24,25-epoxy group in their side chain. 24,25-epoxywithanolide D (20) was rst isolated from Physalis angulate, 45 and its structure was recently conrmed by X-ray diffraction analysis of its acetyl derivative (21). 46 The structure of virginol A ( 22) 26 was elucidated on the basis of chemical and physicochemical evidence, and X-ray diffraction analysis.…”

Withanolide Structural Revisions by 13C NMR Spectroscopic Analysis Inclusive of the γ-Gauche Effect

“…However, differences caused by OH-14α or OH-14β include the following: (1) OH-14α shields C-12 (∼4−7 ppm decrease), whereas OH-14β does not; (2) the shielding effect on C-9 by OH-14α (∼7 ppm decrease) is greater than OH-14β (∼3−5 ppm decrease), and this is due to the axial−axial positions of H-9 and OH-14α. These empirical rules are consistent with the published data, as revealed by the 13 C NMR comparison of different types of steroids 43−64 (Figure 3 and Table S3, Supporting Information): androstanes [testosterone (43), 51 14α-hydroxytestosterone (44), 52,53 androst-4-ene-3,17dione (45), 51 and 14α-hydroxyandrost-4-ene-3,17-dione (46) 51 ]; pregnanes [3β-hydroxy-5β-pregnan-20-one (47), 54 5β-pregnane-3,20-dione (50), 54 and progesterone (53); 54 their corresponding 14α-hydroxy derivatives: 3β,14α-dihydroxy-5β-pregnan-20-one (48), 54 14α-hydroxy-5β-pregnane-3,20-dione (51), 54 and 14α-hydroxyprogesterone (54); 54 or 14β-hydroxy derivatives: 3β,14β-dihydroxy-5β-pregnan-20-one (49), 55 14β-hydroxy-5β-pregnane-3,20-dione (52), 55 and 14βhydroxyprogesterone (55) 56 ]; cholestane 56; 57 cardenolide 57; 58 and withanolides [withacoagulin E (14), 13 withanolide G (39), 16 withaferin A (58), 59 physapubenolide (59), 18 5,6deoxywithanolide D (60), 34 ixocarpanolide (61), 60 14αhydroxyixocarpanolide (62), 60 physalolactone B (63), 61 and 1-deacetyl-14α-hydroxyphysalolactone B (64) 62 ]. Therefore, the 14-hydroxy group affects the chemical shifts (C-7, C-9, and C-12), and the chemical shifts (C-9 and C-12) can be utilized to accurately determine the orientation of the 14-hydroxy group in steroids.…”