Biological Activities of Manzamines

Together with eudistomins, also manzamine alkaloids have received special attention due to their biological activities [2]. Manzamine alkaloids, mostly isolated from sponges, are characterized by a unique polycyclic ring system, which may biogenetically derive from ammonia, Cio and C3 units, and tryptamine [307]. In the majority of the manzamine alkaloids, the multicyclic units are condensed with tryptamine to form P-carboline. The first representative of this class of alkaloids, manzamine A (71), was isolated as hydrochloride salt from an Okinawan sponge ETfl/zc/oun sp. [308]. 

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... 

Evaluation of the biological properties of these compounds in the literature demonstrates a wide range of activities. For example, the manzamines and ircinals have been shown to possess antileukemic and antibacterial activity xestocyclamine A shows inhibition against the enzyme Protein Kinase C, but compounds with cytotoxicity or other activities can also be found. 

The singular structure of manzamine has also attracted enormous attention from a synthetic point of view. The formidable synthetic challenge coupled with the significant biological activity has stimulated many synthetic studies, culminating in the synthesis of several fragments and subunits of this alkaloid. 

At least one thousand publications have described the isolation or synthesis of the natural products of indole in the last decade, including many complex indole alkaloids, especially those with novel skeletons, potent biological activities, or posing synthetic challenges. Manzamine A (1) (for recent isolations see [1-8] for recent syntheses see [9-11]) and vinblastine (2) (for recent isolations see [12-17] for recent syntheses see [18-22]) (Fig. 1) are two recent typical examples of great interest for both their syntheses and biological applications. 

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