The Synthesis of Complex and Diverse Compounds from Natural Products
The majority of commercially available compound screening collections consist of simple, planar compounds that lack significant stereochemistry. While such compounds are suitable to modulate certain biological targets, they are generally not effective against more complex targets (e.g., protein-protein interactions, protein-DNA interactions). In addition, the majority of FDA approved anticancer and antibacterial agents are complex natural products, compound with physiochemical properties vastly different from those in compound screening collections. We have initiated a program whose goal is to create complex and diverse compounds. To do this, we take readily available natural products, and in ~5 or fewer chemical steps change them to compounds that are complex, but diverse from the parent natural product and from each other.
Gibberellic acid was rapidly converted into six highly diverse and complex scaffolds.
Ring distortion afforded many complex structures starting from Adrenosterone.
Ring distortion afforded many complex structures starting from Quinine.
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