Of shermilamine

An examination of the composition of polyaromatic alkaloids of the mollusk Chelynotus semperi and an unidentified tunicate, both collected from Mante channel, Pohnpei, resulted in the identification of shermilamine B [129] and kuanoniamines A-D [130-133] (105). Shermilamine was originally found as a metabolite of a tunicate of the genus TruUdanmon (106). 

Dehydrokuanoniamine B (127) and shermilamine C (128) were isolated from a Cystodytes sp. from Fiji. Their structures were determined by analysis of spectroscopic data. These compounds displayed dose-dependent inhibition of proliferation in human colon tumour cells in vitro [142]. Shermilamines D (129) and E (130) were... 

Since the discovery of amphimedine by Schmitz and co-workers in 1983 [36], the polycyclic alkaloids based on the pyrido[, /]acridine skeleton have emerged as a well-defined class of marine metabolites, with significant biological activities, isolated from sponges and tunicates [37]. The less common group of sulfide pyridoacridines were only obtained from tunicates and they include the shermilamines, the varamines-lissoclins-diplamine group, and tintamine, another polycyclic alkaloid closely related to them. 

The shermilamines constitute a group of alkaloids characterized by a thiazinone ring attached to the pyridoacridine ring system. Shermilamine A (36) was the first known compound of this series and was isolated by Scheuer et al. from the tunicate Trididemnum sp. [38]. The complete... 

Shermilamines B (37) and C (38) (and also diplamine 46) showed dose-dependent inhibition of proliferation in HCT cells in vitro and inhibited the topoisomerase (TOPO) II-mediated decatenation of kinetoplast DNA (kDNA) in a dose-dependent manner [41]. These results suggest a possible cytotoxicity mechanism for these compounds. Furthermore, shermilamine B also displayed cytotoxicity against KB cells [43] and was reported as a potent regulator of cellular growth and differentiation, affecting cAMP-mediated processes [44]. 

Thiazole-containing pyridoacridines are a group of fused ring alkaloids having a pyrido[4,3,2-w, ]thiazolo[3,2-6]acridinium skeleton related to shermilamines, varamines and diplamine, which were discussed in the sulfide section [37]. The pyridoacridines have a characteristic UV absorption pattern [A.max(MeOH) 245, 307, and 361 nm], which is highly sensitive to the pH of the medium. 

Tunicates are the only marine invertebrates in which alkaloid biosynthesis has been extensively investigated (189). In addition to the eudistomins, described below, the tripeptide tunichromes have been investigated, by Nakanishi and coworkers at Columbia University, in the solitary tunicate Ascidia nigra (191) and shermilamine, a benzo-3,6-phenanthroline alkaloid, has been studied in Cystodytes dellechiajei, by Steffan and coworkers at the University of Munich (192). The origin of the (3-carboline ring system of the eudistomins has been studied, by Baker s group at Florida Tech, in Eudistoma olivaceum (193, 194). 

Thiazine containing alkaloids are relatively rare in Nature, but they range in structural complexity from simple monocyclic derivatives such as chondrine and benzothiazines such as the aplidinones, to more complex tri- and polycyclic compounds exemplified by ansafhiazin and the shermilamines. On the other hand, the simplest N,S-heterocycle - the 5-membered thiazole - is relatively common in Nature, and, for example, plays a vital role in the function of thiamine (vitamin Bi). Thiazole rings also occur in important biologically active natural products such as the epothilones (Figure 1). 

The shermilamines are a group of pentacyclic alkaloids based on the well-known p5uido[4,3,2-m ]acridine framework (Figure 16) (03M104). The... 

Figure 16 Structures of the shermilamines, thiazinone pyrido[4,3,2-mn]acridine alkaloids.

Shermilamine A-B. The first of the acridine-derived alkaloids to be reported were shermilamine A and B (32) (Carroll et al. 1989). Using long-range... 

Nordercitin, Dercitamine, Dercitamide, and Cyclodercitin. A series of three pyridoacridine alkaloids related to the shermilamines were reported by Gunawardana et al. (1989). In assigning the structures of nordercitin (R = NMe2) dercitamine (R = NHMe), and dercitamide (R = NHCOEt) (33), isolated from two deep-water marine sponges of the family Pachastrellidae, the authors used a combination of COLOC and HMBC spectra. The report did not compare results of the two experiments nor unfortunately did it... 

Eudistones A and B were obtained from an undetermined species of Eudistoma from the Seychelles Islands. Tintamine, shermilamine E and cydoshermil-amine D are three sulfur-containing pyridoacridines. These new alkaloids were extracted from Cystodytes viola-tinctus, whose specific name refers to the animal s color and whose origin is the lagoon of Mayotte. Tintamine is the first example of a pyridoacridine associated with a tropolone and shermilamine E is a rare example of an N-oxide derivative isolated from a marine organism. 

The species Cystodytes deUechiajei exists in the Western Mediterranean (Spain) as four chemotypes of different colors that are due in large part to distinct compositions of different pyridoacridines. The purple chemotype contains mainly shermilamine B, kuanoniamine D and their deace-tylated derivatives, the blue and green chemotypes contain ascididemin and 11-hydroxyasddidemin, and the brown chemotype contains only ascididemin (Lopez-Legentil et al., 2005 Bontemps et al., 2010). 

Ciufolini, M.A. and Shen, Y.C. (1995) Total synthesis of cystodytin J, diplamine and shermilamine B. Tetrahedron Lett., 36, 4709-4712. 

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