First Total Synthesis of the Cytotoxic Carbazole Alkaloid Excavatine‐A and Regioselective Annulation to Pyrano[2,3‐a]carbazoles and [1,4]Oxazepino[2,3,4‐jk]carbazoles

Abstract

We describe the first total synthesis of the cytotoxic carbazole alkaloid excavatine‐A. The carbazole framework was constructed through double C–H bond activation of a diarylamine by using our palladium(II)‐catalyzed oxidative cyclization. Treatment of the intermediate 8‐hydroxycarbazoles with prenal and different additives led either to pyrano[2,3‐a]carbazoles or to [1,4]oxazepino[2,3,4‐jk]carbazoles. The pyran annulation was investigated to determine the influence of substitution pattern, additives, and reaction time on the selectivity.

Trends in carbazole synthesis – an update (2013–2023)

“…the Knölker group being a main contributor in this field. [194][195][196][197][198][199][200][201][202][203][204][205][206][207][208][209][210]211,212 Mechanistically, the carbon-carbon bond formation is initiated by two sequential electrophilic attacks of the palladium catalyst on diarylamine 82, generating six-membered palladacycle 84. Reductive elimination generates the desired carbazole 83, and a palladium(0)-species, which is reoxidised in situ by a co-catalyst (e.g., copper(II) acetate, oxygen, air, tert-butyl hydroperoxide etc.).…”

“…A representative selection of successfully completed total synthesis is shown in Scheme 26, 188–193 with the Knölker group being a main contributor in this field. 194–210,211,212 Mechanistically, the carbon–carbon bond formation is initiated by two sequential electrophilic attacks of the palladium catalyst on diarylamine 82 , generating six-membered palladacycle 84 . Reductive elimination generates the desired carbazole 83 , and a palladium(0)-species, which is re-oxidised in situ by a co-catalyst ( e.g.…”

Total Synthesis of Aqabamycin G, a Nitrophenyl Indolylmaleimide Marine Alkaloid from Vibrio sp. WMBA

“…Hence, joining of 6 and 18 was attempted under Pd­(OAc) 2 catalysis, with NaOAc as base. This provided O -benzyloxy-aqabamycin G ( 19 ) in 18% yield, along with the proto-dediazonated byproduct 20 , , and recovered 6 (49% yield). Instead of a hydrogenolysis, , 19 was submitted to a more specific thiol-mediated debenzylation with PhSH in (CF 3 CO) 2 O, giving aqabamycin G (58% yield).…”

Site-Specific Synthesis of Carbazole Derivatives through Aryl Homocoupling and Amination

“…Carbazoles are a distinctive class of compounds that have formidable impact due to diverse biological activities [1][2][3] including anticancer [4][5][6][7] and antiparasitic roles. 8,9 There have been numerous studies on carbazoles and their synthetic routes due to their excellent material properties for use as optoelectronic devices, 10 solar cells, 11,12 photo-initiator catalysts, 13,14 chemical and biosensors, 15 luminogens, 16,17 and organic light-emitting diodes [18][19][20][21] (Figure 1).…”