Chromone-Thiocoumarin Transmutation Enabled by Lawesson's Reagent.

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Selective modification of molecular skeletons is crucial for discovering new drug leads.
• Chromone derivatives are common starting materials, but their transformation into other biologically relevant scaffolds can be challenging.

Purpose of the Study:

• To develop an efficient protocol for the skeletal transmutation of chromone derivatives into thiocoumarins.
• To explore the synthetic utility of this transformation in medicinal chemistry.

Main Methods:

• Chromone derivatives were reacted with Lawesson's reagent under heating in toluene.
• The reaction proceeds via a cascade of ring opening, rearrangement, and cyclization.
• Mechanistic studies utilized 18O-labeled substrates to trace atom origins.

Main Results:

• A series of thiocoumarins were successfully synthesized from chromone precursors.
• The protocol demonstrated synthetic utility through gram-scale synthesis and late-stage modification of estrone.
• Mechanistic studies confirmed the origin of the silicon-bound oxygen atom.

Conclusions:

• This study presents an efficient method for converting chromones to thiocoumarins, a biologically privileged scaffold.
• The developed skeletal remodeling strategy is valuable for lead compound discovery and modification in medicinal chemistry.