A formal total synthesis of the telomerase inhibitor dictyodendrin B

Abstract

Abstract-Formal synthesis of the telomerase inhibitory marine pyrrolocarbazole alkaloid dictyodendrin B is described. The key features are consecutive palladium-catalyzed cross-coupling reactions and intramolecular reductive coupling reaction to construct the pyrrolo[2,3-c]carbazole framework.

Synthesis and Applications of Dihydropyrrolocarbazoles

“…Synthesis of precursor 128 of dictyodendrin A from pentasubstituted pyrrole 126 . Construction of cycle B either by SmI 2 ‐promoted pinacol coupling of keto‐aldehyde 129 or by aldol condensation from 132 , …”

“…[37] Construction of cycle B either by SmI 2 -promoted pinacol coupling of keto-aldehyde 129 or by aldol condensation from 132. [40,41] core. [38,39] The strategy was based on the thermal formation of a nitrene intermediate from azides 135a-e prepared from the pinacolboronate synthesized from bromo intermediates 134ae (Scheme 23).…”

Synthetic Approach to Dictyodendrins: A Facile Synthesis of Pyrrolo[2,3‐c]carbazole, Pyrrolodibenzothiophene, and Benzo[e]indole

“…The solvent was removed followed by column chromatographic purification (hexane/EA, 8 Entry 2). Upon completion of the reaction (monitored by TLC), the mixture was poured into ice water (20 mL) and then was acidified with concentrated HCl (2 mL).…”

“…Fürstner and co-workers reported the synthesis of dictyodendrin-inspired natural product-like targets. The same group also reported [8] a formal total synthesis of dictyodendrin B by using a SmI 2 -mediated intramolecular cyclization of 3-(2-anisoylpyrrol-3-yl)indole-2-carbaldehyde followed by subsequent dehydration using acetic anhydride. Ishibashi and co-workers [7] achieved the synthesis of the pyrrolo[2, 3-c]carbazole core by an intramolecular condensation of a suitably substituted 3-(2-anisoylpyrrol-3-yl)-2-cyanomethyl-indole.…”

Total Synthesis of Dictyodendrins by the Gold‐Catalyzed Cascade Cyclization of Conjugated Diynes with Pyrroles

“…[1] These compounds belong to af amily of marine indole alkaloids and have been reported to inhibit the activity of telomerase,t hus making them potential anticancer agents.D ictyodendrins F-J were first isolated by Capon and co-workers in 2012 from the southern Australian marine sponge Ianthella sp.T hese compounds exhibited inhibitory activity towards b-site amyloidcleaving enzyme 1(BACE1), and are therefore recognized as potential targets for the treatment of Alzheimersd isease. [3] Subsequently, the research groups of Ishibashi, [4] Tokuyama, [5] Jia, [6] Gaunt, [7] Yamaguchi/Itami/Davies, [8] and Ready [9] disclosed total syntheses of these interesting natural products.A common feature of these strategies was the introduction of several optimally placed substituents prior to the construction of the pyrrolo[2,3-c]carbazole core.W ee nvisaged that the development of ad iversity-oriented synthesis for the construction of these natural products on the basis of the earlystage construction of the core structure,f ollowed by the introduction of the different substituents,w ould be more amenable to medicinal applications. [3] Subsequently, the research groups of Ishibashi, [4] Tokuyama, [5] Jia, [6] Gaunt, [7] Yamaguchi/Itami/Davies, [8] and Ready [9] disclosed total syntheses of these interesting natural products.A common feature of these strategies was the introduction of several optimally placed substituents prior to the construction of the pyrrolo[2,3-c]carbazole core.W ee nvisaged that the development of ad iversity-oriented synthesis for the construction of these natural products on the basis of the earlystage construction of the core structure,f ollowed by the introduction of the different substituents,w ould be more amenable to medicinal applications.…”