Ritterazines isolation

Moser, B. (2008) Review of cytotoxic cephalostatins and ritterazines isolation and synthesis./. Nat. Prod., 71, 487—491. 

Fukuzawa, S., Matsunaga, S., and Fusetani, N., Isolation and structure elucidation of ritterazines B and C, highly cytotoxic dimeric steroidal alkaloids, from the tunicate Ritterella tokioka, J. Org. Chem., 60, 608, 1995. 

Ritterella tokioka Kott, a tunicate of the family Polyclinidae, collected from the Izu Peninsula 100 km southwest of Tokyo, on extraction and partitioning between a number of solvent systems followed by repeated chromatography, afforded another series of bis-steroidal pyrazine alkaloids, ritterazines A-M (26-38). Structures of these alkaloids were found to be related to the cephalostatins isolated from the hemichordate Cephalo-discus gilchristii. 

Ritterazine J (35), [a]D 66° (CH3OH), was the most highly oxygenated isolate, as revealed by the molecular formula C54H76N2On. The eastern hemisphere had an identical structure to that of the western hemisphere, except for C-7, which bore no hydroxyl group. 

The biosynthesis of these compounds seems to occur in two phases (1) coupling of two steroids via a pyrazine linker, and (2) relatively unselective oxidation at various positions. Some of these compounds are related to others by simple processes the hydration of cephalostatin 1 to its hemiketal form cephalostatin 9 the dehydration of cephalostatin 2 to an enone, which in turn may be an intermediate to cephalostatin 6 the skeletal rearrangement of ritterazine B to ritterazine A, which may be acid catalyzed and the pairs of ritterazines epimeric at C-22. One can speculate whether such reactions are non-enzymatic transformations occurring in the organism or even during the isolation procedure. 

In 1994, a steroid-pyrazine dimer was reported [5] from an unexpected source. Fuse-tani s group isolated ritterazine A, with an ED50 of 10 pg mL against P388, from the tunicate Ritterella tokioka collected off Japan. Twelve other ritterazines have since been described [6] (Fig. 2), including one homodimer, ritterazine K. A possible mecha-... 

The ritterazines are highly ox ygenated dimeric steroidal alkaloids isolated by Fusetani and co-workers from 1994 to 1997 from the colonial tunicate Ritterella tokioka (family Policlinidae) [107, 108],... 

The 45 members of the cephalostatin/ritterazine family isolated to date, together with a growing number of analogues and related monosteroidal antineoplastics provide the basis for elueidating some structure -activity relationships (SAR) of these potent cytotoxins and for diseovering the minimum pharmacophore required to maintain potent cancer cell growth inhibitory behavior. 

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