Indole alkaloids bearing the tetracyclic indoline scaffolds of 1H-pyrrolo[2,3-d]carbazole have shown fascinating chemical diversity and significant biological activities. The development of efficient synthetic methodologies for such a tetracyclic scaffold remains highly desirable in both synthetic chemistry and medicinal chemistry. This review outlines key strategies for the construction of the tetracyclic indoline scaffolds in total syntheses of many indole alkaloids. The key strategies include nucleophilic additions, Diels-Alder reactions, radical cyclizations, and palladium-catalyzed coupling reactions. The representative examples and their applications in the total syntheses are described here and discussed in depth.
N-Fluorobenzenesulfonimide was identified for the first time as a unique Ag(i)-catalyst attenuator in the annulation of a tryptamine-derived ynesulfonamide to an azepino[4,5-b]indole.
Spiro[indoline-3,4′-piperidine]
is a significant structural
scaffold in numerous polycyclic indole alkaloids with a variety of
bioactivities. In this study, a synthetic strategy was developed to
access spiro[indoline-3,4′-pyridin]-2-yl carbamate via an AgOTf/PPh3-catalyzed tandem cyclization of tryptamine-ynesulfonamides.
The unique feature of this strategy is the efficient intermolecular
capturing of the in situ generated spiroindoleninium intermediates
with carbamates, leading to the diastereoselective syntheses of spiro[indoline-3,4′-pyridin]-2-yl
carbamate derivatives. A broad scope of this cyclization was demonstrated
by a variety of tryptamine-ynesulfonamide substrates and several carbamates.
A plausible mechanism of this reaction was proposed.
A common strategy was developed to access both indolizino[8,7-b]indole and indolo[2,3-a]quinolizine derivatives from tryptamine-N-ethynylpropiolamide substrates in a switchable fashion via tuning both the electronic effects and steric effects.
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