Total Synthesis of Chondramide C and Its Binding Mode to F‐Actin

Abstract

Actin glue: An E‐selective ring‐closing metathesis as the key step allowed the solid‐phase‐based total synthesis of the F‐actin stabilizer chondramide C as well as the establishment of its hitherto unknown stereochemistry. A strong influence of the polyketide configuration was revealed in cellular assays. Docking studies on the F‐actin filament structure led to a detailed model of the binding site.

Myxobacterial secondary metabolites: bioactivities and modes-of-action

“…117,118 Two other mixed metabolites, rhizopodin 30 and chivosazol 26, cause the opposite effect, actin depolymerization. Rhizopodin has a particularly dramatic impact on cells, provoking the formation of long, branching and reticular runners, which resemble the rhizopodia of certain protozoa (hence the compound's name).…”

Asymmetric Friedel–Crafts alkylation of indoles with 2-nitro-3-arylacrylates catalyzed by a metal-templated hydrogen bonding catalyst

“…A crystal structure of the major diastereomer of product 3h confirmed the assigned absolute and relative configurations Due to the presence of indole in many natural products and pharmaceutically active compounds, chiral indole-containing compounds constitute potentially useful synthetic building blocks. [19][20][21] We therefore investigated further conversions of this class of Friedel-Crafts alkylation products and used the product 3c as our model system. 22 Importantly, as can be seen from the results in Scheme 2, the enantioselectivities were only reduced slightly in the course of the developed transformations.…”

Chapter 2. Chondramides and Chivosazoles – Two Metabolites Which Interfere with the Actin Cytoskeleton

“…Compound 18 was constructed using solid-phase synthesis and all four diastereomers were accessed by esterification of 18 with the four diastereomers of homoallyl alcohol 19a-d to form 20a-d. 9,10 The key step involved the synthesis of an a-branched trisubstituted double bond. Remarkably, the double bond geometry established during the metathesis reaction depended significantly on the configuration of the C6 and C7 stereocentres.…”