Advances in polycyclization cascades in natural product synthesis

Abstract

Cascade reactions are among the most powerful means to achieve the construction of multiple ring systems in a single step. This tutorial review describes recent advances in the use of polycyclization cascades in natural product synthesis.

Gold(I)-Catalyzed Cyclization–3-Aza-Cope–Mannich Cascade and Its Application to the Synthesis of Cephalotaxine

“…Cascade reactions are useful and interesting to organic chemists as they furnish complex compounds from simple molecules in single experimental operations. Natural and pharmaceutical compounds are more efficiently synthesized using cascade reactions because fewer synthetic steps are involved . For example, many natural alkaloids have been synthesized using 2-aza-Cope–Mannich cascades, in which the [3,3]-sigmatropic rearrangement of an iminium 1 and subsequent Mannich cyclization of an enol-iminium intermediate 2 affords a 3-acylpyrrolidine 3 as a common product skeleton (Scheme ).…”

Visible Light-Induced Pericyclic Cascade Reaction for the Synthesis of Quinolinone Derivatives with an Oxabicyclo[4.2.0]octene Skeleton

“…P ericyclic cascade reactions have a wide range of applications in the synthesis of natural products and biological molecules. 1 For example, the tandem cyclization strategy comprised of pericyclic reactions was adopted in the syntheses of hirsutellone, 2 artochamins, 3 pleocarpenone, 4 valparicine, 5 parvineostemonine, 6 and daphnilactone 7 (Figure 1), reducing the synthesis steps. Pericyclic reactions mainly include electrocyclic reactions, cycloadditions, and sigmatropic rearrangements.…”

“…A second energy transfer leads to retro-4π-electrocyclization of 5a, forming eight-membered ring product 2a. Then, 2a undergoes [1,5]-H shift to form intermediate 6a. 19 Considering that the hydrogen atoms attached to C1 and C2 of 3a adopt a cis-conformation, a photoinduced disrotatory 4π-electrocyclization is likely to occur in the transformation of 6a to 3a, which is consistent with the Woodward−Hoffmann rules.…”

“…20 In summary, a visible light-induced pericyclic cascade reaction has been developed. This reaction proceeds through [2 + 2]-photocycloaddition, base-promoted elimination, retro-4π-electrocyclization, [1,5]-H shift, and 4π-electrocyclization, affording quinolinone derivatives with an oxabicyclo[4.2.0]-Table 2. Substrate Scope Investigations a a A solution of 1 (0.2 mmol), thioxanthone (10 mol %), and t BuONa (1 equiv) in anhydrous MeCN (20 mL) was irradiated by violet LED (410−420 nm) at rt under argon atmosphere for 12 h. b 1.108 g of 1a was applied.…”

Synthesis of tetracyclic spiroindolines by an interrupted Bischler–Napieralski reaction: total synthesis of akuammicine

“…These exceptional advantages over traditional stepwise procedures make them particularly suited to efficiently access complex molecules such as natural products. 1 Consequently, the use of cascade reactions in total synthesis is a well-established and prolific field that is constantly expanding in both methodology and scope, covering polyketides, 2 alkaloids, 3 terpenes, 4 and steroids. 5 Owing to their abundance, structural variety, and diverse biological activities, indole alkaloids occupy a prominent position among natural products ( Fig.…”