Green Construction Of Spiroheterocyclic Indolones And Their Application In The Synthesis Of Maremycin

Spirocyclic indolone building blocks are found to be widely present in natural products and pharmaceuticals and are key synthetic precursors for many biologically active oxidized indole natural products and drugs.How to construct spirocyclic indolone skeleton has attracted the attention of many research groups,and most of the traditional methods for constructing spiroheterocyclic indolone skeleton need to undergo substrate modification,complex reaction process and the use of organic oxidants and toxic metal residues,endangering people’s health and polluting the living environment,so that the application of spiroindole oxide compounds is limited.Therefore,there is an urgent need to develop a simple,green and efficient way to construct such skeleton structures.Based on the potassium persulfate complex salt-halide green chemical system developed in the early stage of our group,this paper mainly studies the methodology of oxone-halide green chemical system without transition metal participation to catalyze the green and efficient synthesis of spirocyclic indodone compounds by high chromatic alcohol and tryptamine derivatives,and successfully applies the new method to the synthesis of active natural products maremycin A and B.In the introduction,spirocyclic indolones and their skeleton structure,construction status and oxone-halide green chemical system were reviewed.The methodology of oxone-halide-catalyzed synthesis of spirocyclic indolone was carried out,and the optimal reaction conditions were determined by screening and optimizing the halogen source,feeding ratio and other conditions: 0.2 mmolol 1a or 1m,10 mol% KI,2.0 m L tert-butanol/water(v/v = 20: 1),0.44 mmol oxone,60 °C,reaction for 20 hours.Under optimal conditions,the universal range of substrates was investigated from the aspects of N-protection group and different substitutions on aromatic rings,and 33 spirocyclic indolone compounds were synthesized with the highest yield of 88%.Based on the previous research and the experimental results obtained,the possible mechanism of the reaction is proposed.In order to prove the effectiveness of the new method,derivatization synthesis such as sequential halogenation of hyperchromol derivatives was carried out,and the corresponding products were successfully obtained.In addition,the application of the new method in the synthesis of natural products maremycin A and B was also explored.The new method developed in this study was used to construct the core skeleton structure of natural product molecules maremycin A and B in one step12,and successfully realized the research work on the full synthesis of natural product molecules maremycin A and B.The results show that this study successfully reports a new method for efficient construction of spirocyclic indolone backbone using monopotassium persulfate composite salt-halogen anion green chemical system.The new method has the characteristics of mild reaction conditions,green catalytic system,simple operation,green,efficient and environmental protection.The catalytic reaction was used instead of the stoichiometric reaction,and the skeleton structure of spirocyclic indolone was constructed in one step by one-pot boiling,which improved the reaction efficiency and reduced the use of organic reagents.The use of non-toxic and harmless oxone-halide green system to participate in the reaction,green environmental protection,in line with the concept of green chemistry.In this project,the core skeleton structure of the natural product molecules maremycin A and B12 was successfully constructed by this method,simplifying the total synthesis steps of3-hydroxyindolone alkaloids maremycin A and B.This project provides a new strategy for researchers to construct the skeleton structure of spirocyclic indolone and realize the core skeleton of the synthesis of 3-hydroxyindolone alkaloid maremycins.