Manzamines marine sponges

Structures of marine sponge alkaloids manzamines and related compounds 97H(46)765. 

Marine sponges are a source of an array of polycyclic diamine alkaloids of common biogenetic origin. This class of secondary metabolites has been the subject of four previous reviews [4-7]. Therefore, the present review will include literature reports previously not discussed, dealing with the isolation, structure determination, biological activities, and total synthesis of polycycUc diamine alkaloids isolated from marine sponges. This review will not include guanidine alkaloids [8,9] or the manzamine alkaloids [10,11], since these compounds have been recently reviewed elsewhere. Only polycycUc... 

The basic alkaloid in Pilocarpus jaborandi (Rutaceae) is pilocarpine, a molecule of which contains an imidazole nucleus and is also used as a clinical drug. During alkaloid synthesis, L-histidine can produce the manzamine nucleus (Figure 27). These alkaloids are quite widespread, though they were first isolated in the late 1980s in marine sponges. They have an unusual polycyclic system and a very broad range of bioactivities. Common alkaloids with this nucleus include manzamine A, manzamine B, manzamine X, manzamine Y, sextomanzamine A and so on. 

Manzamine alkaloids can be isolated from marine sponges. They often contain /3-carboline. This group has a diverse range of bioactivities. It also has its own way of establishing its structures. An intramolecular Diels-Adler reaction for manzamines has been proposed. The a is bisdihydropyridine (derived probably from amonia), and the (3 is intramolecular cycloaddition in a pentacyclic... 

Ohtani, I. Ichiba, T. Isobe, M. Kelly-Borges, M. ScheuCT, P.J. (1995) Kauluamine an unprecedented manzamine dimer from an Indonesian marine sponge, Prianos sp. J. Am. Chem. Soc., 117, 10743-4. 

The manzamines are novel polycyclic p-carbolinealkaloids reported first by Higa and coworkers in 1986,73 from the Okinawan marine sponge Haliclona. Manzamines have been shown to have a diverse and interesting range of bioactivity including cytotoxicity and antimicrobial and insecticidal activities.74 75 Isolation ( 0.85% dry weight) and structure elucidation, aided by 15N-NMR spectroscopy, of the known manzamine A (59), and the... 

Fused tetracyclic and pentacyclic alkaloids constitute a relatively new class of natural products isolated mostly from ascidians and sponges. Cytotoxic, antimicrobial and antiviral activities have been reported for many of these compounds. The manzamine alkaloids, Fig. (33) are characterized by a complex pentacyclic diamine linked to C-l of P-carboline moiety. Manzamine have been isolated mainly from six different genera of marine sponges Haliclona, Pellina, Xestospongia, Ircinia, Pachypellin and Amphimedon. 

Manzamine-type alkaloids were also reported in another samples of marine sponges, eg., the Okinawan Amphimedon sp. [252-254], Pachypellina sp. [255], and a novel alkaloid called hyrtiomanzamine from Hyrtios erecta, with interesting immunosuppressive activity [256]. From... 

For the structurally more complex molecule 18, only the Schrock conditions worked. Compound 18 has been synthesized as a synthetic precursor of the marine alkaloid nakado-marin A (19 [14]) from the marine sponge Amphimedon sp. Nakadomarin A (19) belongs to the manzamine alkaloids, which are also targets of biomimetic syntheses [15], For both strategies, there is still some distance to go. 

Manzamine A and epothilone A are two natural products with promising antitumor activities. Manzamine A is isolated from marine sponges, whereas epothilone A is isolated from myxo-bacteria. 

Hydroxymanzamine A was isolated from the Indonesian sponge PachypeUina sp. with moderate antitumor and anti-HSV-II activity, in 1994 ]39]. It was named as manzamine Gin some literature ]20]. 6-Hydroxymanzamine A (called manzamine Y in some references [20,41]) and 3,4-dihydromanzamine A were isolated from the Okinawan marine sponge Amphimedon sp. The Philippine sponge Xestospongia (=Acanthostrongylophora) ashmorica Hooper yielded manzamine A N-oxide, 3,4-dihydromanzamine A N-oxide, and 6-deoxymanzamine X ]10]. 

In a continued search for new manzamine alkaloids, 1,2,3,4-tetrahydromanza-mine B (35) and ma eganedin A (36) has been isolated from the same species of the Okinawan marine sponge Amphimedon sp. [45,51]. Ma eganedin A has a unique methylene carbon bridge between N-2 and N-27. Their stmctures, including the absolute configuration, were elucidated from spectroscopic data. 

Dihydromanzamine J (37) was isolated from the Okinawan marine sponge Amphimedon sp. along with manzamine M and 3,4-dihydro-6-hydroxymanzamine A [40]. Manzamine J N-oxide was obtained from the Philippine sponge Xestospongia... 

Manzamine C (40) is characterized by a 2-ethyl-N-azacycloundec-6-ene connected to C-1 of a p-carboline. To date, only two analogs of this type of manzamine have been reported. Manzamine C was obtained from the same species Haliclona sp. that yields manzamine A [37a[. Keramamine C (41) was isolated from an Okinawan marine sponge Amphimedon sp. [18[. 

Xestomanzamine A (46) and B (47) were isolated from the Okinawan marine sponge Xestospongia sp. with manzamine X [41], des-N-Methylxestomanzamine A... 

Tab. 8.1 Marine sponges yielding manzamines and related alkaloids. ...

Polycyclic amine alkaloids (3-alkylpiperidine alkaloids) containing a complex skeleton with several macrocyclic rings have been isolated from marine sponges. They include manzamines, sarains, haliclamine A and ingenamines. Their structures, synthesis and biochemical aspects have been recently reviewed [35]. Our focus, therefore, is on the biogenetic origin of the bis-pyridinium macrocycle and on the role of precursors in their biosynthesis, as summarized in the retrosynthetic analysis for manzamines demonstrated schematically in Fig.(23). 

ABSTRACT Marine sponges have frequently afforded a wide variety of alkaloids. Polycyclic amines (3-alkylpiperidine alkaloids) are secondary metabolites that are profusely found in Indo-Pacific sponges. These compounds contain complicated skeletons with several macrocyclic rings. One of the first members of these exclusively sponge-derived alkaloids is manzamine A, which was described independently by Riga in 1986 and by Nakamura in 1987. This compound possesses an unusual pentacyclic diamine fused ring joined to Cl of a )S-carboline moiety. 

Pentacyclic manzamine alkaloids from marine sponges... 

Four new bioactive manzamines have been obtained from the Philippine Marine Sponge Xestospongia ashmorica [67]. Compoimd 82 is the iV-oxide derivative of manzamine A, while 84 is the 7V-oxide of 3,4-dihydromanzamine. Among these secondary metabolites, the isolation of 85 was reported, which was found to be the 6-deoxy derivative of manzamine X. 

An unprecedented manzamine dimer, kauluamine (90), was isolated from the Indonesian marine sponge Prianos sp. 90 is an unsymmetrical dimer composed of tetracyclic and pentacyclic ring systems. Efforts to obtain a crystalline structure or to run an INADEQUATE experiment were unsuccessful. Thus the structure was elucidated by NMR methods, mainly on the basis of extensive 2D-NMR experiments, DQFCOSY, HOHAHA, HMQC, HMBC, and HMQC-HOHAHA [102,103]. 

Keramaphidin C and Keramamine C, Plausible Biogenetic Precursors of Manzamine C from an Okinawan Marine Sponge. Tsuda, M Kawasaki, N. and Kobayashi, J. Tetrahedron Lett. 1994, 35, 4387. 

Ircinals A and B from the Okinawan Marine Sponge Ircinia sp. Plausible Biogenetic Precursors of Manzamine Alkaloids. Kondo, K. Shigemori, H. Kikuchi, Y. Ishibashi, M. Sasaki, T. and Kobayashi, J. J. Org. Chem. 1992, 57, 2480. 

Four New Bioactive Manzamine-Type Alkaloids from a Philippine Marine Sponge Xestospongia ashmorica. Edrada, R. A. Proksch, P. Wray, V. Witte,... 

Kauluamine An unprecedented Manzamine Dimer from an Indonesian Marine Sponge, Prianos sp. Ohtani L L Icchiba, T. Isdbe M. Kelly-Borges, M. and Scheuer P. Tennen Yuki Kagobutsu Toronkai 1995, 37, 236. 

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