A Submarine Journey: The Pyrrole-Imidazole Alkaloids

Abstract

In his most celebrated tale “The Picture of Dorian Gray”, Oscar Wilde stated that “those who go beneath the surface do so at their peril”. This sentence could be a prophetical warning for the practitioner who voluntarily challenges himself with trying to synthesize marine sponge-deriving pyrrole-imidazole alkaloids. This now nearly triple-digit membered community has been growing exponentially in the last 20 years, both in terms of new representatives and topological complexity – from simple, achiral oroidin to the breathtaking 12-ring stylissadines A and B, each possessing 16 stereocenters. While the biosynthesis and the role in the sponge economy of most of these alkaloids still lies in the realm of speculations, significant biological activities for some of them have clearly emerged. This review will account for the progress in achieving the total synthesis of the more biologically enticing members of this class of natural products.

Chemical defense against predators and bacterial fouling in the Mediterranean sponges Axinella polypoides and A. verrucosa

“…In other sponges of the genus Axinella and the related genus Agelas, these activities are frequently mediated by pyrrole-imidazoles, a metabolite class thus far isolated only from marine sponges (Forte et al 2009) including A. verrucosa (Cimino et al 1975, Aiello et al 2006, Haber et al 2010), but apparently absent in A. polypoides (Cimino et al 1975). Our results indicate that this chemical difference relates to distinct defensive strategies against microbial fouling and predator deterrence in these 2 sponges.…”

Total Synthesis of Palau’amine

“…1 palau amine (1) was originally isolated from a sponge, Stylotella agminata, in 1993 by Scheuer as a novel class of pyrrole imidazole alkaloids, 2 and its proposed structure was revised in 2007. 3 Since the initial structure elucidation and the later revision, palau amine (1) has been an attractive synthetic target due to its intriguing molecular architecture and signi cant biological properties including antifungal, antitumor, and immunosuppressive activities. The immunosuppressive activity has been of particular interest, and two studies on its mode of action have been reported.…”

C-N bond forming reactions in the synthesis of substituted 2-aminoimidazole derivatives

“…For example, Leucetta and Clathrina-derived alkaloids, which have been isolated from marine sponges during the last three decades, were reported to exhibit antibacterial, anti-inflammatory, anticancer, and antiviral activity. [1][2][3] Different types of substituted 2-aminoimidazoles, including the pyrrole-2-aminomidazoles of the oroidin family and their synthetic analogs 4,5 possess anti-biofilm activities, 6,7 while 2-arylamino or iminoimidazolidines (e.g. clonidine), known hypertensive agents, 8 have also been evaluated as α 2 -adrenoceptor antagonists for the treatment of depression ( Figure 1).…”