A biosynthetically inspired synthesis of (-)-berkelic acid and analogs
Christopher F Bender1, Christopher L Paradise1, Vincent M Lynch2
1Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9038, USA.
Abstract:
We describe a complete account of our total synthesis and biological evaluation of (-)-berkelic acid and analogs. We delineate a synthetic strategy inspired by a potentially biomimetic union between the natural products spicifernin and pulvilloric acid. After defining optimal parameters, we executed a one-pot silver-mediated in situ dehydration of an isochroman lactol to methyl pulvillorate, the cycloisomerization of a spicifernin-like alkynol to the corresponding exocyclic enol ether, and a subsequent cycloaddition to deliver the tetracyclic core of berkelic acid. Our studies confirm that the original assigned berkelic acid structure is not stable and equilibrates into a mixture of 4 diastereomers, fully characterized by X-ray crystallography. In addition to berkelic acid, C22-epi-berkelic acid, and nor-berkelic acids, we synthesized C26-oxoberkelic acid analogs that were evaluated against human cancer cell lines. In contrast to data reported for natural berkelic acid, our synthetic material and analogs were found to be devoid of activity.
Related Concept Videos
01:29Amino Acid Biosynthetic Pathways
01:30Mechanism of Breathing I: Inspiration
The respiratory system, an essential network for breathing, comprises the conducting and respiratory zones, each playing a crucial role in the overall process of respiration. Let us explore the detailed mechanism of inspiration, or inhalation, which is the first phase of the respiratory cycle.
Pathway of Air during Inspiration
During inspiration, air enters our body through the nose or mouth and moves through the conducting zone,...
02:17Synthesis and Decomposition Reactions
03:42Amino acids
02:36Transfer RNA Synthesis
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
01:15Dehydration Synthesis
Dehydration synthesis (also called a condensation reaction) is the chemical process in which two molecules covalently link together to form a new molecule, along with the release of a water molecule. Many physiologically important compounds form by dehydration synthesis reactions, such as complex carbohydrates, proteins, DNA, and RNA.
Synthesis of carbohydrates
Sugar molecules are covalently linked together by dehydration synthesis. During the reaction, the hydroxyl (-OH) group from...