Marine manzamines

The asyrrunetric total synthesis of nakadomarin A, a marine manzamine alkaloid 05Y200. 

Nakagawa, M., Nagata, T., Ono, K., and Nishida, A. (2005) The asymmetric total synthesis of nakadomarin A, a marine manzamine alkaloid. J. Synth. Org. Chem. Japan, 63, 200-210. 

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

Biogenesis of manzamine alkaloids ((3-carboline marine alkaloids) 97H(46)765, 97YGK1114. 

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... 

The central five-membered ring of Manzamine A (315), a member of a family of antileukimic and antibacterial marine polycyclic alkaloids, has been constructed using intramolecular azomethine ylide technology (88). Model studies on the construction of the central ABC rings, by condensation of the aldehyde 316 prepared by standard chemistry with sarcosine ethyl ester, furnished the desired ABC ring system as a single diastereoisomer in 45% yield (Scheme 3.105). 

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). 

The Ramberg-Backlund rearrangement was the key step in the total synthesis of the marine alkaloid manzamine C by D.l. MaGee and E.J. Beck. The azacycloundecene ring was stereoselectively formed by exposing the a-chloro sulfone to a strong base. The use of weaker bases either resulted in no reaction or gave rise to mixtures of ( )- and (Z)-alkenes. 

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