3-Alkylpyridines alkaloids

Andersen, R.J., Van Soest, R.W.M., and Kong, F. (1996) 3-Alkylpyridine alkaloids isolated from marine sponges in the order Haplosclerida, in Alkaloids Chemical and Biological Perspectives, vol. 10 (ed. S.W. Pelletier), Pergamon Press, Amsterdam, Boston, London, pp. 301-355. 

Tsukamoto, S., Takahashi, M., Matsunaga, S., Fusetani, N., and Van Soest, RW.M. (2000) Hachijodines A-G seven new cytotoxic 3-alkylpyridine alkaloids from two marine sponges of the genera Xestospongia and Amphimedon. J. Nat. Prod., 63, 682-684. 

Cutignano, A., Tramice, A., De Caro, S., ViHani, G., Cimino, G., and Fontana, A. (2004b) Biogenesis of 3-alkylpyridine alkaloids in the marine mollusc Haminoea orbignyana. Angew. Chem. Ira. Ed., 42, 2633-2636. 

Teruya, T, Kobayashi, K., Suenaga, K., and Kigoshi, H. (2005) Phormidinines A and B, novel 2-alkylpyridine alkaloids from the cyanobacterium Phormidium sp. Tetrahedron Lett., 46,4001-4003. 

Arai, M., Ishida, A., Setiawan, A., and Kobayashi, M. (2009) Haliclonacyclamines, tetracyclic alkylpyridine alkaloids, as anti-... 

We present an overview of the structures for 3-alkylpyridine and 3-alkylpyridinium compounds that have been isolated, taking into account the structural characterization of alkylpyridinium compounds and discussing the central role played by mass spectrometry. Concerning their synthesis, both the natural pathways and organic synthesis of pyridinium alkaloids are reviewed. Synthetic aspects of 3-alkylpyridines have been taken into account only where relevant for structural modifications or for the assignment of absolute configurations. Finally, biological activities of both 3-alkylpyridine and 3-alkylpyridinium compounds and the potential use of the latter are discussed. 

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. 

The proposed biogenetic pathways (See Section 3) to 3-alkylpiperidine sponge alkaloids that have complex structures and nitrogen heterocycles at the piperidine or tetrahydropyridine oxidation states all proceed through a partially reduced Ws-3-alkylpyridine... 

Pyrinodemin A was reported in 1999 as a cytotoxic pyridine alkaloid isolated from the sponge Amfhimedon sp. collected in Okinawa. The planar structure of this alkaloid was composed of a unique cyclopent[r]isoxazo-lidine connected with a bis-3-alkylpyridine based on the MS and NMR data. Location of the Z olefin [5c 129.3 (2C), C-16 and C-17 ] was assigned from the chemical shift of the two vinyl carbons (C-15 and C-18, ... 

Since nicotine is the most abnndant and best known tobacco alkaloid, its pyrolysis has been thoronghly stndied [Woodward et al. (4275a), Jarboe and Rosene (1923a)]. More recent work [Kabnraki et al. (2006)] on the pyrolysis of nicotine and vari-ons alkylpyridines has resnlted in a proposed mechanism for the thermal degradation of nicotine. .. Schmeltz [Schmeltz et al. (3499)] also stndied nicotine and identified a nnmber of previonsly nnreported componnds in the nicotine pyrolysates. .. These inclnded pyrrole, acenaphthene, indole, skatole, and anthracene and/or phenanthrene. However, the presence of dibenzacridines and dibenzcarbazole, previonsly reported in nicotine and pyridine pyrolysates, conld not be confirmed [Van Duuren et al. (4027)]. 

The first tentative biogenetic hypothesis was suggested by Cimino et al. for the saraines, haliclamines, xestospongins, and petrosins. The origin of these alkaloids can be envisaged as coming from reduced bis-3-alkylpyridine macrocycles. 

Alkylated pyridines play an important role in chemical technology as well as in nature. Nicotine is a natural alkylpyridine derivative, found in the tobacco plant this alkaloid was used from the 17 th century until the 1950 s as a plant protection agent. 

Reviews of specific groups of these alkaloids, for instance, simple 3-alkylpyridine (or pyridinium) alkaloids or manzamine-related alka-loids, have also been published. 

Bracher, F. and Papke, T. (1996) Alkylpyridines. 111. Total synthesis of both enantiomers of the antineoplastic marine alkaloid niphatesine D. Monatsh. Chem., 127, 91-95. 

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