First synthesis of an ABCE ring substructure of daphnicyclidin A

Abstract

The ABCE tetracyclic ring system of daphnicyclidin A was prepared using an intramolecular (4+3) cycloaddition of an oxidopyridinium ion as the key step. This route consists of a 10-step synthesis...

Daphnicyclidin Alkaloids 2001–2023

“…The even more elaborated 3-hydroxypyridinium cation 154 was also qualified for the intramolecular (4 + 3) cycloaddition (Scheme 15). [30] In the event, the fragile 1,3-diene moiety was masked as 3-sulfolene. Using high temperature conditions, cycloelimination of sulfur dioxide exposed the corresponding 1,3-diene and enabled formation of the ABCE-tricyclic building block 155 for daphnicyclidin A by intramolecular ( 4 In 2023, She et al [31] published the synthesis of the ABCtricyclic platform molecule 164 prepared from Li's established building block 163 [32] (Scheme 16), and its elaboration to the advanced building block 175 for daphnicyclidin A (Scheme 17).…”

“…The even more elaborated 3‐hydroxypyridinium cation 154 was also qualified for the intramolecular (4+3) cycloaddition (Scheme 15). [30] In the event, the fragile 1,3‐diene moiety was masked as 3‐sulfolene. Using high temperature conditions, cycloelimination of sulfur dioxide exposed the corresponding 1,3‐diene and enabled formation of the ABCE‐tricyclic building block 155 for daphnicyclidin A by intramolecular (4+3) cycloaddition.…”

Synthesis of the 5–6–7 Tricyclic Core of Daphnicyclidin-Type Alkaloids via a Tiffeneau–Demjanov Ring Enlargement Strategy

“…Three years later, the same group developed an intramolecular photocatalytic decarboxylation conjugate addition to prepare the requisite cycloheptanone C ring, and a 5–7–5 (ACE) tricyclic intermediate of daphnicyclidin A and 2-deoxymacropodumine A was produced . In 2022, the Harmata group reported a concise synthesis of the 5–6–7 (ABC) tricyclic skeleton of daphnicyclidin A and its unique cycloheptanone C ring was efficiently assembled by an intramolecular (4+3) cycloaddition of the oxidopyridinium ion . More recently, the A. Li group and the C. Li group independently reported the total syntheses of daphnicyclidine-type alkaloids.…”

“…They share a unique 5–6–7–5–7 pentacyclic framework with a central compact polysubstituted cyclohept-2-enone C ring, and this ring is deduced to be derived from the corresponding cyclohexanone ring of calyciphylline A-type DAs based on biogenesis analysis (Figure ). Due to the great challenges encountered in the construction of its functionally dense cyclohept-2-enone C ring, the syntheses of daphnicyclidin-type DAs have rarely been explored, and only a few works on the synthesis of their partial ring system were reported − before 2022. In 2009, the Overman group reported an elegant construction of the 5–6–7–7 (A–D) tetracyclic skeleton of daphnicyclidin-type DAs in which the cycloheptanone C ring was assembled via an aza-Cope–Mannich reaction .…”

“…8b In 2022, the Harmata group reported a concise synthesis of the 5−6−7 (ABC) tricyclic skeleton of daphnicyclidin A and its unique cycloheptanone C ring was efficiently assembled by an intramolecular (4+3) cycloaddition of the oxidopyridinium ion. 9 More recently, the A. Li group 10 and the C. Li group 11 independently reported the total syntheses of daphnicyclidinetype alkaloids. In both works, biomimetic ring expansion strategies were employed at a late stage to transform the 6−5 spirocyclic subunit of calyciphylline A-type DAs (colored blue in Figure 1) into the required 7−5 fused ring system of daphnicyclidin-type DAs (colored red in Figure 1).…”