Manzamines antimicrobial activity

The expedient total synthesis of tetracyclic core of the enantiomer of (-)-nakadomarin A (77) was reported by Zhai and co-workers recently. This marine natural product, related to manzamine, was found to be toxic to murine lymphoma LI210 cells and displayed antimicrobial activity. The fimctionalized tetracycle 78 contained a trisubstituted alkene moeity which could not be hydrogenated selectively due to the presence of the more reactive furan ring. This alkene was unresponsive to treatment with TFA/EtaSiH, and hydroboration followed by protonation (using HBr or HOAc) was also unsuccessful. This quandary was resolved by conversion to the secondary alcohol 79 (using a hydroboration/oxidation procedure) which was then converted to xanthate 80, which could be readily deoxygenated in good yield to 81. 

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. 

Manzamines comprise a new group of /3-carboline alkaloids having polycyclic ring systems, the provenance of which is problematical as there appears to be no obvious biogenetic path. Manzamine A (180) was isolated from an Okinawan sponge (Haliclona sp.) and shown to exhibit antitumor activity. Its structure and absolute configuration were determined by X-ray analysis (150). From an Okinawan sponge (Pellina sp.) keramamines A (180) and B (181) were isolated as antimicrobial substances (151), and keramamine A was found to be identical with manzamine A. 

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