Home R & D Chem One-Step Synthesis of Pyrrolo-Coumarins Using Ethyl Isocyanoacetate

One-Step Synthesis of Pyrrolo-Coumarins Using Ethyl Isocyanoacetate

July 12, 2023

🔬 Researchers have developed a new methodology for the synthesis of pyrrolo-coumarins, a class of bioactive compounds found in marine natural products and synthetic compounds. The new method involves a one-step cycloaddition-lactonization reaction using ethyl isocyanoacetate as a key reagent. This approach provides a convenient and efficient route to access pyrrolo-coumarins with potential biological activities.

Summary

🔹 Pyrrolo-coumarins, including lamellarins and ningalin B, are a class of marine alkaloids with diverse biological activities.
🔹 Synthetic routes for pyrrolo-coumarin synthesis typically involve multistep processes, such as condensation, cyclization, and lactonization.
🔹 Previous methods utilized transition-metal-catalyzed dehydrogenative coupling or cyclization of prefunctionalized coumarins.
🔹 The new one-step strategy involves the use of ethyl isocyanoacetate as a four-atom synthon for the cycloaddition-lactonization reaction.
🔹 The optimized reaction conditions include the use of specific reagent ratios and temperature.
🔹 The method demonstrated good generality with various 2-hydroxychalcone substrates, delivering pyrrolo-coumarins in moderate to high yields.
🔹 The strategy can also be extended to the synthesis of chromenopyrrole-carboxylates and further functionalization of the obtained pyrrolo-coumarins.

The researchers developed a novel approach for the synthesis of pyrrolo-coumarins, a class of compounds with promising biological activities. Previous methods for pyrrolo-coumarin synthesis involved multiple steps, but the new strategy enables their construction in a single step. The key reagent in this method is ethyl isocyanoacetate, which acts as a four-atom synthon. The reaction conditions were optimized, resulting in good yields of the desired pyrrolo-coumarins.

The researchers tested the generality of their method by using various 2-hydroxychalcone substrates. These substrates contained different substituents at both the ketone and salicylaldehyde parts. The reaction successfully delivered pyrrolo-coumarins with moderate to high yields for a wide range of substrates. Notably, the method allowed for the scalability of the reaction in gram scale.

Furthermore, the researchers demonstrated the synthetic utility of the obtained pyrrolo-coumarins by subjecting them to Pd(II)-catalyzed cross-coupling reactions. These reactions provided access to fused pentacyclic pyrroles, expanding the structural diversity and potential applications of the synthesized compounds.

In conclusion, the developed one-step cycloaddition-lactonization strategy using ethyl isocyanoacetate represents an efficient and economical approach to synthesize pyrrolo-coumarins. The method is versatile and can be further used to make compounds that are practical and adaptable in pharmaceutical discovery and chemical biology studies.