Guanidinium Alkaloids

Hepatotoxins include microcystins, which are cyclic heptapeptides (Fig. 5.1a) and cylindrospermopsin, a sulfated guanidinium alkaloid (Fig. 5. lb). Microcystins bind to certain protein phosphatases responsible for regulating the distribution of cytoskeletal proteins (Zurawell et al. 2005 Leflaive and Ten-Hage 2007). Hepatocytes exposed to microcystins eventually undergo cellular deformation, resulting in intra-hepatic bleeding and, ultimately, death (Carmichael 2001 Batista et al. 2003). In contrast, cylindrospermopsin appears to have a different mode of activity, possibly involving inhibition of protein or nucleotide synthesis (Codd et al. 1999 Froscio et al. 2003 Reisner et al. 2004). Nevertheless, microcystins are the most common cyanotoxins isolated from cyanobacterial blooms (Sivonen and Jones 1999). 

The highly toxic guanidinium alkaloid tetrodotoxin was first isolated from the Japanese puffer fish, Fuga rubipes. In the early 1960s, a guanidinium alkaloid was isolated from eggs of the California newt Taricha torosa and named tarichatoxin (185). It proved identical with tetrodotoxin from puffer fish (186 see Ref. 5 for a historical review). Tetrodotoxin and other guanidinium toxins, namely, chiriquitoxin and the zetekitoxins, have been shown to occur in other amphibians. 

Gephyrotoxins, 242-245 Guanidinium alkaloids, 264-269 chiriquitoxin, 267-268 tetrodotoxin, 264-267 zetekitoxin, 268-269... 

Stellettadine A a new acylated bis-guanidinium alkaloid which induces larval metamorphosis in ascidians from a marine sponge Stelletta sp. Tetrahedron Lett., 37, 5555-5556. 

L. E. Overman, J. Am. Chem. Soc. 2005, 127, 15652-15658. Total synthesis of (-)-crambidine and definition of the relative configuration of its unique tetracyclic guanidinium core, (c) F. Cohen, L. E. Overman, /. Am. Chem. Soc. 2006, 128, 2594-2604. Evolution of a strategy for the synthesis of structurally complex batzeUadine alkaloids. Enantioselective total synthesis of the proposed structure of batzeUadine F and structural revision. 

Generally, the chiral quaternary ammonium salts, derived from cinchona alkaloids [26, 28, 29, 46, 56-60] and C2-symmetric chiral binaphthyl or biaryl structures [61-68, 71-73, 77], were demonstrated to be very enantioselective catalysts for the asymmetric alkylation of 65a, and provided the corresponding chiral a-amino acids in over 95% ee in most cases. The tartaric acid-derived catalysts 48a [81] and 52 [84] and chiral guanidinium salts 53 [85] and 54 [86] were also found to be suitable for this alkylation reaction. However, in terms of catalytic activity, only a... 

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