Benzosceptrins A and B with a Unique Benzocyclobutane Skeleton and Nagelamide S and T from Pacific Sponges

Abstract

Four new dimeric pyrrole-2-aminoimidazole alkaloids have been isolated from the Pacific marine sponges Agelas cf. mauritiana and Phakellia sp. They include the unusual C2 symmetrical benzosceptrins A (4) and B (5), which each possess a unique benzocyclobutane skeleton and nagelamides S (6) and T (7). Their structures and relative configuration were elucidated from spectroscopic data. Plausible biogenetic paths for these compounds are also proposed in this paper.

Biomimetic Synthesis of Marine Pyrrole‐2‐Aminoimidazole and Guanidinium Alkaloids

“…The synthesis of (+)-phakellin hydrochloride (90) was achieved in 18 steps. This synthesis provided the first example of the non-intuitive Overman [3,3] sigmatropic rearrangement applied to an enamide (87).…”

“…Several interesting and challenging molecules are currently under chemical and biological studies. Recent isolation of novel P-2-AI dimeric members, benzosceptrin A (10) [3] and stylissazole C (177) [70], demonstrates the incredible potential of P-2-AI metabolites to generate original molecules and rare organic architectures. While benzosceptrin A shows a highly strained benzocyclobutane, stylissazole C is one of the first example of dimerization involving exclusively N-C bond formations (Scheme 7.34).…”

“…The biogenesis of P-2-AIs can be studied at two levels of complexity: (i) from the pool of amino acids to clathrodin (1) and dispacamide (4,5) skeletons or (ii) from the latter to more complex structures via polycyclizations or dimerizations (Scheme 7.2). In 2001, our group postulated that the tautomeric equilibria of the aminopropenylimidazole portion of oroidin (3) were the key processes involved in the formation of both polycyclic monomers and cyclized dimers [1]. This is certainly a consequence of the corresponding ambivalent nucleophilic/electrophilic behavior of oroidin derivatives.…”

Assembly of the Bis(imidazolyl)propene Core of Nagelamides C and S by Double Grignard Reaction

“…[1,2] Important biological activities include fish feeding deterrency [3] and anti-biofilm activity. [4] A particular group is formed by pyrrole-imidazole alkaloids containing two C 11 N 5 subunits such as nagelamides C (2), [5] S (3) [6] and J (5) [7] or ageliferin (4, Figure 1), which continue to be challenging targets for total synthesis. [8] Bis(imidazolyl)-allyl-or -alkylamines of type 1 can be identified as core structures, which may function as strategic intermediates for total synthesis.…”

Pyrrole Aminoimidazole Alkaloid Metabiosynthesis with Marine Sponges Agelas conifera and Stylissa caribica

“…Detailed field experiments support the contention that oroidin ( 3b ) and related molecules, longamide and dispacamide, most likely serve as the primary chemical defenses of Stylissa and Agelas sponges. [8] Sceptrin ( 1a ) is formally derived by [2+2] cycloaddition of 3a , and benzosceptrins A-C ( 4a-c ) [9] are cyclized analogs of 1 . The potent antitumor agents, agelastatins A ( 2a ) and B ( 2b ) can be envisioned as a product of enzyme-mediated cyclization-oxidation of 3a,b .…”