Manzamine alkaloid

Manzamine alkaloids ((3-carboline derivatives from sponges), syntheses and synthetic approaches 98T6201. 

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

Scheme 25 Sequential formation of 13- and 8-membered azacycles in Martin s total synthesis of ircinal A (129) and related manzamine alkaloids [78]...

Clark and coworkers utilized enyne RCM for constructing the AB ring fragment of the manzamine alkaloids (Scheme 83) [177]. Exposing metathesis precursor 423 and ethylene gas to catalyst A provided bicycle 424 in near quantitative yield. Regioselective hydroboration of the vinyl group in 424, followed... 

For a total synthesis of ircinal A and related manzamine alkaloids via RCM, see Scheme 25... 

Magnier E., Langlois Y. Manzamine Alkaloids, Syntheses and Synthetic Approaches Tetrahedron 1998 54 6201-6258... 

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... 

Nishida A, Nagata T, Nakagawa M (2006) Strategies for the Synthesis of Manzamine Alkaloids. 5 255-280... 

We have been interested in the synthesis of nakadomarin A 1 [2], which belongs to manzamine alkaloids [3] by two different routes (Routes A and B). 

L-isoleucine L-leucine L-lysine Lysine-derived alkaloids Imidazole alkaloids Manzamine alkaloids True alkaloids... 

Figure 27. L-histidine and the nuclei of imidazole and manzamine alkaloids.

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... 

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. 

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. 

In the synthesis of manzamine alkaloids, the AA of 8 proceeded with remarkable selectivity, given the fact that the double bond is electronically not differentiated [12]. The formation of 9 as the exclusive product can be understood by a transfer of the nitrogen group via the least hindered trajectory to the alkene, i.e. the less-substituted position of the double and equatorial approach. 

Scheme 5. Application of the AA toward the synthesis of manzamine alkaloids.

For manzamine A, Martin et al. developed a strategy for the construction of the eight-membered ring E [15], Pandit et al. succeeded in the formation of the 13-membered ring D [18]. The efforts culminated recently in the total synthesis of manzamine A and related manzamine alkaloids, employing the ring-closing metathesis reaction as a key step [16]. Thus, 49 is converted into 50 with a yield of 67 % (Scheme 8). 

The unique structure and extraordinary bioactivity of manzamine alkaloids have attracted great interest from synthetic chemists as one of the most challenging natural product targets for total synthesis. Great efforts have been made to achieve total synthesis of manzamine A and related alkaloids. Methodological studies towards the synthesis of manzamine structural units have also been reported [31-33]. 

There are several reviews referring to manzamine alkaloids [7,31-35]. In this chapter, we will review the structure and source of manzamine alkaloids including the large-scale preparation of manzamine alkaloids for preclinical evaluation. We also discuss the detailed synthesis and bioactivities of manzamine alkaloids. 

Carboline-containing Manzamine Alkaloids 8.2.1.1 Manzamine A Type... 

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