Novel Naamidine‐Type Alkaloids and Mixed‐Ligand Zinc(II) Complexes from a Calcareous Sponge, Leucetta sp., of the Coral Sea

Abstract

(1 6.111.95)As compounds from a calcareous sponge, Leucetta sp., of the Coral Sea, we isolated a series of novel naamidine-type alkaloids, 6-10, which are oxidized at a single benzylic position. We also report on the first marine, mixed-ligand metal complex 5 and on the first natural metal complexes 3 and 4 derived from classical naamidines, i.e.. 1 and 2. The latter are also present in free form in the sponge.

Total synthesis and cytotoxicity of Leucetta alkaloids

“…As initial targets, our attention was directed to naamidine G ( 4 ), 27 one of several molecules isolated by Pietra and coworkers. 28 The crude extract containing these molecules was described as being cytotoxic, but no details were described for the individual purified molecules and thus access to synthetic versions would help address the question of which of these several derivatives were responsible for the cytotoxicity. The synthesis commenced from the diiodoimidazole 14 which was subjected to transmetallation with EtMgBr.…”

“…= 195–196 °C (lit. 28 m.p. = 94 °C); 1 H NMR: δ = 10.04 (br, 1H), 7.10 (d, J = 8.7 Hz, 2H), 6.90 (d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.7 Hz, 2H), 6.77 (d, J = 8.7 Hz, 2H), 3.89 (s, 2H), 3.88 (s, 2H), 3.76 (s, 6H), 3.47 (s, 3H), 3.15 (s, 3H); 13 C NMR: δ = 162.3, 158.6, 158.3, 155.7, 146.5, 145.0, 135.7, 131.5, 129.4, 129.1, 129.0, 127.0, 114.3, 114.1, 55.4, 32.3, 30.0, 28.7, 24.7; IR (KBr, cm-1): = 3241, 2931, 2835, 1788, 1738, 1656, 1511, 1451, 1302, 1248, 1177, 1036, 744, 697; HR-ESIMS ( m/z ): Calcd.…”

The enantiomeric separation of 4,5-disubstituted imidazoles by HPLC and CE using cyclodextrin-based chiral selectors

“…Considering the potential pharmacological importance of natural products, researchers are continually searching for new, undiscovered molecules. Recognising that about 70% of the earth's surface is water, many of these researchers have intuitively turned to the seas and marine organisms in search of these compounds (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Currently, one group of organisms which has come under scrutiny is marine sponges (10 -18).…”

Two new imidazole alkaloids from Leucetta chagosensis sponge

“…A groups of imidazole alkaloids have been isolated from genus Leucetta (Carmely and Kashman, 1987;Carmely et al, 1989;Gross et al, 2002;Fu et al, 1997;Dunbar et al, 2000;Plubrukarn et al, 1997;Akee et al, 1990;Carroll et al, 1993;Mancini et al, 1995;Crews et al, 2003;Alvi et al, 1993;He et al, 1992) included among these are naamines (Carmely and Kashman, 1987;Carmely et al, 1989;Gross et al, 2002;Fu et al, 1997;Dunbar et al, 2000), isonaamines (Carmely and Kashman, 1987;Carmely et al, 1989), naamidines (Carmely and Kashman, 1987;Alvi et al, 1993;He et al, 1992) and isonaamidines Alvi et al, 1993). The compounds were named after the Bay of Naama where the sponge was first collected (Carmely et al, 1989), in addition to kealiiquinone (Fu et al, 1997;Akee et al, 1990), leucettamine (Carmely et al, 1989;Crews et al, 2003), preclathridine (Alvi et al, 1993;He et al, 1992), leucosolenamines A and B (Ralifo et al, 2007), (2E, 6Z, 9Z)-2-methyl-2, 6,9-icosatrienal (Watanabe et al, 2000), dorimidazole A, leucettamol , calcaridine A (Edrada et al, 2003), leucettamide , and halogenated natural products (Tsukamoto et al, 2008).…”

“…The compounds were named after the Bay of Naama where the sponge was first collected (Carmely et al, 1989), in addition to kealiiquinone (Fu et al, 1997;Akee et al, 1990), leucettamine (Carmely et al, 1989;Crews et al, 2003), preclathridine (Alvi et al, 1993;He et al, 1992), leucosolenamines A and B (Ralifo et al, 2007), (2E, 6Z, 9Z)-2-methyl-2, 6,9-icosatrienal (Watanabe et al, 2000), dorimidazole A, leucettamol , calcaridine A (Edrada et al, 2003), leucettamide , and halogenated natural products (Tsukamoto et al, 2008). Some of these alkaloids show very important biological activities as cytotoxic (Gross et al, 2002;Tsukamoto et al, 2007), antimicrobial (Carmely and Kashman, 1987;Carmely et al, 1989;Gross et al, 2002;Mancini et al, 1995), inhibition of Ubc13-Uev1A interaction and anticancer activities (Tsukamoto et al, 2008). Previous investigation of the current sample Leucetta chagosensis, has led to isolation of naamines F, and G in addition to series of kealiinine A, B and C compounds (Hassan et al, 2004).…”