A 4-nitro-3-arylpyrrole Platform for the Divergent Synthesis of Marine Natural Products: Ningalins and Lamellarins

Abstract

Pyrrole is a key structural motif found in numerous bioactive molecules and natural products. Herein, we report an efficient and scalable synthesis of polysubstituted 3-arylpyrroles via a Barton-Zard reaction between chloronitroolefins and isocyanoacetates. The reaction was promoted by tetramethylguanidine in ethanol, tolerating a wide range of aryl and heteroaryl substituents, as well as sterically demanding groups. Mechanistic studies revealed a unique in situ transesterification pathway for specific isocyanoacetate derivatives. The synthetic utility of this methodology is further demonstrated through a concise, gram-scale total synthesis of marine natural products Ningalin B and Lamellarin L, underscoring its potential to accelerate the development of structurally related bioactive compounds.