3-Alkylpiperidine alkaloids

Sponges in the order Elaplosclerida have been the source of a family of more than 100 3-alkylpiperidine alkaloids (see Figure 9) that all appear to have been formed via a common biosynthetic pathway which is unique to marine... 

Figure 9 3-Alkylpiperidine alkaloids isolated from sponges in the order Haplosclerida...

Alkylpiperidine alkaloids from marine sponges of Haploselerida order 96MI4. 

Andersen RJ, van Soest RWM, Kong F (1996) 3-Alkylpiperidine alkaloids isolated from marine sponges in the order Haplosclerida. In Alkaloids chemical and biological perspectives. Pergamon, New York, p 301... 

The motuporamines are considered as manzamine-related alkaloids owing to their structural relationship with manzamine C (57), the simplest alkaloid of this family of compounds. Baldwin and Whitehead have proposed a plausible biogenesis for these 3-alkylpiperidine alkaloids, suggesting that they could be formed from three basic building blocks ammonia, a C3 unit, and a Cio unit [54]. The motuporamines, which contain a spermidine-like side chain instead of the alkylated p-carboline substructure of manzamine C, appear to be biogenetically derived from the same precursors, ammonia, acrolein, and a long-chain dialdehyde involved in the Baldwin-Whitehead pathway (Scheme 9.2). 

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). 

Alkylpiperidine Alkaloids Isolated from Marine Sponges in the Order Haplosclerida... 

The monomeric structural unit of the 3-alkylpiperidine alkaloids is readily apparent in a number of simple 3-alkylpyridines isolated from marine sponges. In all known examples, the 3-alkyl component of the monomeric unit is attached to a primary amine, methyl amine, methoxy amine, methoxy methyl amine, imine oxide or oxime methyl ether functionality at the distal terminus. 

Two groups of complex polycyclic 3-alkylpiperidine alkaloids have tricyclic or tetracyclic core structures resulting from the formation of two or three transannular bonds between the two piperidine rings of a bis-3-alkylpiperidine macrocycle. Saraine A (72), the... 

The biogenetic origins of three groups of 3-alkylpiperidine alkaloids from bis-3-alkylpiperidine macrocyclic precursors is obscured by rearrangements in the carbon skeletons and hydrolytic cleavages of C-N bonds that are required to convert the macrocyclic precursors to the natural products. As a consequence, it is only possible to find one clearly defined 3-alkylpiperidine residue in the skeletons of these compounds. 

Cimino and co-worker s biogenetic proposal for the formation 3-alkylpiperidine alkaloids... 

A proposed biogenesis for the formation of monomeric, dimeric and oligomeric 3-alkylpiperidine alkaloids. The proposal is based on Baldwin and Whitehead s proposed biogenesis for the manzamines [58]. 

Rearrangement of the ingenamine-type intermediate 126, as shown in Figure 3.10, can lead to the madangamine skeleton [69], The madangamines are the only examples to date of 3-alkylpiperidine alkaloids with rearranged carbon skeletons. 

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