34
B. Schmidt
Scheme 22 Enantioselective total syntheses of stagonolide E (88) and curvulide A (95); completion
of structure assignment for curvulide A
of synthetic curvulide A (95) confirmed the relative configuration of stereocenters
C-4 and C-6 shown in Scheme 22. Thus, 95 is (4R,5R,6R,9R)-configured.
3.3 Seimatopolides
Seimatopolides A (114) and B (115) are ten-membered lactones with a nonyl
substituent at C-9. They were isolated in 2012 by Hiep et al. via bioactivity-guided
fractionation from the culture broth of the fungus Seimatosporium discosioides [125].
This culture broth displayed notable activity in a reporter gene assay for the activation of the γ-subtype of peroxisome proliferator-activated receptors (PPAR-γ).
The PPARs contribute to the regulation of lipid and lipoprotein metabolism, glucose
and fatty acid homeostasis, and the inflammatory response [125]. Activators of these
receptors might therefore be lead structures for potential anti-inflammatory or antidiabetic drugs. The isolated seimatopolides A and B were evaluated for their activating
ability toward PPAR-γ, and half-maximal effective concentrations (EC 50 ) of 1.15 μM
for seimatopolide A (114) and 11.05 μM for seimatopolide B (115) were measured.
Troglitazone, an antidiabetic drug that acts as a PPAR-γ agonist but was discontinued
due to severe side effects, was used as positive control. Its EC 50 value was determined
as 0.44 μM and is therefore in the same potency range as that of seimatopolide A
[125].
B. Schmidt
Scheme 22 Enantioselective total syntheses of stagonolide E (88) and curvulide A (95); completion
of structure assignment for curvulide A
of synthetic curvulide A (95) confirmed the relative configuration of stereocenters
C-4 and C-6 shown in Scheme 22. Thus, 95 is (4R,5R,6R,9R)-configured.
3.3 Seimatopolides
Seimatopolides A (114) and B (115) are ten-membered lactones with a nonyl
substituent at C-9. They were isolated in 2012 by Hiep et al. via bioactivity-guided
fractionation from the culture broth of the fungus Seimatosporium discosioides [125].
This culture broth displayed notable activity in a reporter gene assay for the activation of the γ-subtype of peroxisome proliferator-activated receptors (PPAR-γ).
The PPARs contribute to the regulation of lipid and lipoprotein metabolism, glucose
and fatty acid homeostasis, and the inflammatory response [125]. Activators of these
receptors might therefore be lead structures for potential anti-inflammatory or antidiabetic drugs. The isolated seimatopolides A and B were evaluated for their activating
ability toward PPAR-γ, and half-maximal effective concentrations (EC 50 ) of 1.15 μM
for seimatopolide A (114) and 11.05 μM for seimatopolide B (115) were measured.
Troglitazone, an antidiabetic drug that acts as a PPAR-γ agonist but was discontinued
due to severe side effects, was used as positive control. Its EC 50 value was determined
as 0.44 μM and is therefore in the same potency range as that of seimatopolide A
[125].