2 research outputs found
Kinetically Controlled One-Pot Formation of DEFGH-Rings of Type B Physalins through Domino-Type Transformations
The characteristic DEFGH-ring system of type B physalins has been synthesized by means of a one-pot procedure incorporating domino-type ring transformations. Unexpectedly, we found that introduction of an α-hydroxyester functionality at C17 in ring E allowed the key 7-<i>endo</i> oxy-Michael reaction to proceed. Originally this was thought to be an unfavored process. This afforded the desired caged ring system to be formed in a kinetically controlled manner. Consecutive treatment with AcOH at 100 °C furnished the DEFGH-ring system in one pot
Contribution of Cage-Shaped Structure of Physalins to Their Mode of Action in Inhibition of NF-κB Activation
A library
of oxygenated natural steroids, including physalins,
withanolides, and perulactones, coupled with the synthetic cage-shaped
right-side structure of type B physalins, was constructed. SAR studies
for inhibition of NF-κB activation showed the importance of
both the B-ring and the oxygenated right-side partial structure. The
5β,6β-epoxy derivatives of both physalins and withanolides
showed similar profiles of inhibition of NF-κB activation and
appeared to act on NF-κB signaling via inhibition of phosphorylation
and degradation of IκBα. In contrast, type B physalins
with C5–C6 olefin functionality inhibited nuclear translocation
and DNA binding of RelA/p50 protein dimer, which lie downstream of
IκBα degradation, although withanolides having the same
AB-ring functionality did not. These results indicated that the right-side
partial structure of these steroids influences their mode of action