Total Synthesis of Dictyodendrins B and E, and Formal Synthesis of Dictyodendrin C

Abstract

A full account of the concise total syntheses of dictyodendrins B and E, and the formal synthesis of dictyodendrin C are described. A palladium‐catalysed Larock indole synthesis was used to form the highly substituted indole core, and a palladium‐mediated one‐pot consecutive Buchwald–Hartwig amination/C–H activation reaction was used to construct the key pyrrolo[2,3‐c]carbazole core. Unsuccessful synthetic strategies are also discussed.

A Concise and Scalable Strategy for the Total Synthesis of Dictyodendrin B Based on Sequential CH Functionalization

“…The dictyodendrins are a collection of pyrrolo[2,3‐ c ]‐carbazole‐derived natural products, first isolated in 2003,1 that display interesting inhibitory activities towards telomerases2 and β‐site APP cleaving enzyme 1 (BACE1; APP=amyloid precursor protein) and have received significant interest within the scientific community owing their potential as chemotherapy agents and neurodegenerative probes 3. Furthermore, their complex poly(hetero)aromatic architecture has inspired a number of elegant total syntheses from the groups of Fürstner,4a–c Iwoa and Ishibashi,4d–e Tokuyama,4f–g and Jia 4h–i. We envisaged a possible strategy to the dictyodendrins that involves sequential direct functionalizations of a simple, readily available heteroaromatic building block that would constitute the core of the natural product framework.…”

Synthesis and Applications of Dihydropyrrolocarbazoles

“…The formation of the C cycle to build the pyrrolo[2,3‐ c ]carbazole scaffold was also the strategy applied by the group of Jia for the synthesis of dictyodendrins B, C and E , . The key step was a one‐pot consecutive Buchwald‐Hartwig amination/C–H activation reaction of bromoindoles 141 – 144 (Scheme ).…”

“…The formation of the C cycle to build the pyrrolo[2,3-c]carbazole scaffold was also the strategy applied by the group of Jia for the synthesis of dictyodendrins B, C and E. [43,44] The key step was a one-pot consecutive Buchwald-Hartwig amination/C-H activation reaction of bromoindoles 141-144 (Scheme 25). After debenzylation, compounds 145, 146 and 148 afforded known intermediates 113a-c (Scheme 19, Scheme 23) for the synthesis of dictyodendrins C, B and E, respectively.…”

Total Synthesis of Dictyodendrins A–F by the Gold‐Catalyzed Cascade Cyclization of Conjugated Diyne with Pyrrole

“…[5] In 2005, the Fürstner group disclosed the first total syntheses of dictyodendrins B, C, E, and Ft hrough ac arefully designed stepwise constructiono ft he fused carbazole core (Scheme 1). [6,7] Subsequently,s everal total syntheses of dictyodendrinsh ave been established by the research groupso f Ishibashi (dictyodendrin B), [8,9] Tokuyama( A-E), [10,11] Jia (B, C, and E), [12,13] Gaunt (B), [14] Yamaguchi/Itami/Davies (A and F), [15] Ready (F,H ,a nd I), [3] andH e( F, G, H, and I). [16] Most reported syntheses used strategies based on introducing the requisite substituents prior to construction of the pyrrolo[2,3-c]carbazole core.…”