167832-31-7Relevant articles and documents
Divergent Synthesis of Novel Cylindrocyclophanes that Inhibit Methicillin-Resistant Staphylococcus aureus (MRSA)
Freudenreich, Julien J.,Bartlett, Sean,Robertson, Naomi S.,Kidd, Sarah L.,Forrest, Suzie,Sore, Hannah F.,Galloway, Warren R. J. D.,Welch, Martin,Spring, David R.
, p. 1289 - 1293 (2020)
The cylindrocyclophanes are a family of macrocyclic natural products reported to exhibit antibacterial activity. Little is known about the structural basis of this activity due to the challenges associated with their synthesis or isolation. We hypothesised that structural modification of the cylindrocyclophane scaffold could streamline their synthesis without significant loss of activity. Herein, we report a divergent synthesis of the cylindrocyclophane core enabling access to symmetrical macrocycles by means of a catalytic, domino cross-metathesis-ring-closing metathesis cascade, followed by late-stage diversification. Phenotypic screening identified several novel inhibitors of methicillin-resistant Staphylococcus aureus. The most potent inhibitor has a unique tetrabrominated [7,7]paracyclophane core with no known counterpart in nature. Together these illustrate the potential of divergent synthesis using catalysis and unbiased screening methods in modern antibacterial discovery.
Synthesis of a Coumarin-Based Analogue of Schweinfurthin F
Beutler, John A.,Dey, Patrick N.,Schroeder, Chloe M.,Wiemer, David F.
, p. 16824 - 16833 (2021/11/16)
The natural schweinfurthins are stilbenes with significant antiproliferative activity and an uncertain mechanism of action. To obtain a fluorescent analogue with minimal deviation from the natural structure, a coumarin ring system was annulated to the D-ring, creating a new analogue of schweinfurthin F. This stilbene was prepared through a convergent synthesis, with a Horner-Wadsworth-Emmons condensation employed to form the central stilbene olefin. After preparation of a tricyclic phosphonate via a recent and more efficient modification of the classic Arbuzov reaction, condensation was attempted with an appropriately substituted bicyclic aldehyde but the coumarin system did not survive the reaction conditions. When olefin formation preceded generation of the coumarin, the stilbene formation proceeded smoothly and ultimately allowed access to the targeted coumarin-based schweinfurthin analogue. This analogue displayed the desired fluorescence properties along with significant biological activity in the National Cancer Institute’s 60-cell line bioassay, and the pattern of this biological activity mirrored that of the natural product schweinfurthin F. This approach gives facile access to new fluorescent analogues of the natural schweinfurthins and should be applicable to other natural stilbenes as well.
SYNTHETIC EPIGALLOCATECHIN GALLATE (EGCG) ANALOGS
-
Page/Page column 47; 54, (2013/02/28)
Synthetic polyphenolic compounds of formula (I), their modes of synthesis, and pharmaceutical compositions thereof are provided herein. Use of the compounds and compositions described herein for treating cancer and for treating metabolic disorders is also provided.
