Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties including anti-inflammatory, antiviral, and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures but also their promising therapeutic applications as well as the new general synthetic routes developed during the last years.

Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties, including anti-inflammatory, antiviral and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures, but also new synthetic routes developed during the last years as well as promising therapeutic applications.

The functionalization of aryl alkyl ketones in the alkyl group via enolate chemistry is well-known. Pd-catalyzed cross-coupling reactions of these substrates usually lead to C(sp3)–C bonds via coupling of an enolate and an organic halide (α-arylation). In contrast to this expected reactivity, we report here the selective Pd-catalyzed direct arylation of aryl alkyl ketones on the aromatic ring via C(sp2)–H activation. A variety of acetophenones and alkyl aryl ketones can be functionalized in this way, leaving the methyl(alkyl) group untouched. The key to this selectivity is the use of a cooperating bipyridone ligand that lowers the barrier for C–H activation and the use of a set of reaction conditions that keeps a low concentration of the ionic enolate species in the catalytic cycle. This is supported by a combination of experimental and computational studies, including microkinetic simulations, and analysis of primary and equilibrium kinetic isotope effects (KIEs).