Synthesis of Natural Products by C−H Functionalization of Heterocycless

Abstract

Total synthesis is considered by many as the finest combination of art and science. During the last decades, several concepts were proposed for achieving the perfect vision of total synthesis, such as atom economy, step economy, or redox economy. In this context, C−H functionalization represents the most powerful platform that has emerged in the last years, empowering rapid synthesis of complex natural products and enabling diversification of bioactive scaffolds based on natural product architectures. In this review, we present an overview of the recent strategies towards the total synthesis of heterocyclic natural products enabled by C−H functionalization. Heterocycles represent the most common motifs in drug discovery and marketed drugs. The implementation of C−H functionalization of heterocycles enables novel tactics in the construction of core architectures, but also changes the logic design of retrosynthetic strategies and permits access to natural product scaffolds with novel and enhanced biological activities.

Direct use of hydroxyl ions as an oxygen source for oxidation of isoquinolinium salts to isoquinolinones in water solution

“…Moreover, the optimal temperature and reaction time were found to be 60 1C and 4 h, respectively (Table 1, entries [12][13][14][15][16].…”

“…Therefore, several methods for synthesizing isoquinolinones and quinolinones have been well investigated, including catalyzed annulative coupling, [8][9][10] C-H aminocarbonylation, 11 and C-H bond functionalization. [12][13][14][15][16][17][18][19][20] Although these are considered efficient methods for synthesizing N-heterocycle-based drug molecule skeletons, there are still challenges in controlling the reaction site. Recently, direct oxidation of iminium salts derived from isoquinoline and quinolone using oxidants, such as O 2 , t-BuOOH, and K 3 Fe(CN) 6 , has been proposed as an effective strategy for synthesizing isoquinolinones and quinolinones.…”

Transition metal-catalyzed regioselective functionalization of carbazoles and indolines with maleimides

“…7 In addition, they are widely used as key building blocks for synthesizing bioactive natural products and complex functional heterocycles. 8 Selected examples of naturally occurring and therapeutically active carbazole and indoline molecules are shown in Fig. 1.…”

Application of a transient directing strategy in cyclization reactionsviaC–H activation

“…Transformations involving C–H activation are usually considered an environmentally friendly, low-cost and short-route strategy, and many reactions via C–H activation have been developed in the past more than ten years. 1 However, directing groups need to be pre-installed on the substrates, and often removed after C–H functionalization. To avoid pre-installing and removing directing groups, transient directing groups have been developed.…”