Microwave-Assisted Solid-Phase Synthesis of 5-Carboxamido-N-acetyltryptamine Derivatives

Abstract

[reaction: see text] The synthesis of the indole skeleton of new melatoninergic analogues was realized using solid-phase methodology in association with microwave irradiation. This combination speeds up the solid-phase drug discovery process in rigorously established conditions.

Highlights in the solid-phase organic synthesis of natural products and analogues

“…Finaru et al 16 reported the solid-phase synthesis of the indole core of melatonin analogues under microwave irradiation. The acid-labile Rink linker was chosen for connection of aromatic iodide 58 to polystyrene.…”

The Palladium‐Catalyzed Synthesis of Aromatic Heterocycles

“…This includes work on solid supports [62], the use of heteroaryl spacers [63], the construction of polycyclic products [64], and, more recently, moving from aryl iodides to less expensive aryl bromides and aryl chlorides [65]. The latter was demonstrated by Senanayke and coworkers with the use of the now common bulky electron-rich phosphines to activate the aryl-chloride bond for cyclization (Scheme 6.48).…”

Heterocyclic Chemistry Using Microwave‐Assisted Approaches

“…It is interesting to note that fixed microwave power input provided improved yields over constant temperature conditions (variable microwave power input). This chemistry was successfully extended to a solid-phase format (Rink amide resin) 10 An interesting modification of the Gewald thiophene synthesis combined a onepot, multi-component coupling on solid-phase, with microwave-assisted synthesis 12 . Cyanoacetic acid bound Wang resin was treated with elemental sulphur and a range of aldehydes or ketones under microwave heating (see Chapter 5, Section 5.2.5).…”