Chemistry of β‐Carbolines as Synthetic Intermediates

Abstract

Abstractβ‐Carbolines are present in a wide variety of indole alkaloids that display important biological activities. Here we review the most recent aspects of the chemistry of β‐carbolines with a focus on functionalization of the β‐carboline system and transformations into other interesting compounds. Aromatizations, reductions and alkylations of the heterocyclic system are thus summarized first, followed by methodologies directed towards the formation of additional fused rings. Finally, rearrangements that transform β‐carbolines into other heterocyclic systems are covered.

Recent advances in organocatalytic methods for the synthesis of disubstituted 2- and 3-indolinones

“…However, 9-amino(9-deoxy)epi-hydroquinine (11), a chiral primary amine derived in a single step from the cinchona alkaloid hydroquinine, was proved to be a general and selective catalyst for ketone activations. 57,58 With this catalyst the reaction between alkylidene oxindoles (1a) and a,b-unsaturated ketones (62) afforded the desired product 66 (Scheme 1) in moderate to good yield (24-82%) but excellent selectivity (dr 4 : 1 -4 19 : 1, 89-98% ee).…”

“…For this reason, substituted indoles have been referred to as ''privileged structures'' owing to their excellent binding ability for many receptors with high affinity and a number of approved drugs have this core in their structures. [1][2][3][4][5][6][7][8][9][10][11] The potential clinical significance of enantiomerically pure indole derivatives has led to a demand for efficient asymmetric synthetic methods with the aim to prepare sufficient quantities of the desired natural products and related analogues for biological evaluation and studies on structure-activity relationships. 12 Recently, we reviewed the organocatalytic strategies for the asymmetric functionalization of indoles.…”

Recent Advances in the Synthesis of β-Carboline Alkaloids

“…Numerous representatives of this family show various biological activities [ 3 , 4 , 5 ]. The fascinating diversity of structures and medicinal potential [ 6 ] inherent in them encourage several researchers to deal with the synthesis of β-carboline containing natural products and their synthetic derivatives [ 2 , 4 , 7 , 8 , 9 ]. Several commercial drugs or drug candidates such as vinpocetine, brovincamine, abecarnil, cipargamin, tadalafil, reserpine and lurbinectedin contain this unique framework ( Figure 1 ).…”

One-pot reaction of pyranoindolones with phenylisocyanates: a simple and regioselective approach to β-carbolines

“…[12][13][14][15] The above-mentioned importance of this scaffold requires efficient synthetic methodologies, both for construction of the b-carboline system and for its functionalization. 26,27 Diels-Alder reactions of pyranoindolones with dienophiles are often employed as a key reaction for the synthesis of fused carbazoles 28,29 e.g., access to the alkaloids carbazomycins A and B. 30 Previously, we described synthetic methodologies towards the synthesis of b-carbolinones based on the reactions of pyranoindolones with phenylhydrazine or benzoylhydrazine 31 or utilizing N,N 0 -disubstituted ureas (PhBr, reflux) 32 (Scheme 1).…”