Diazona chinensis

Lindquist N, Fenical W, Van Duyne GD, Clardy J (1991) Isolation and structure determination of diazonamides A and B, unusual cytotoxic metabolites from the marine Ascidian Diazona chinensis. J Am Chem Soc 113 2303-2304... 

DiazonamidM. The halogenated cyclopeptides D. A and B with unusual CC bridges are isolated from the tunicate Diazona chinensis they have strong in vitro cytotoxic activities against the colon tumor HCT-16... 

Diazonamide A (136), a marine secondary metabolite from a colonial ascidian Diazona chinensis, has been synthesized more than once (2008NPR227) Indeed, the original and incorrect structure was also synthesized. Schemes 20 and 21 give some of Nicolaou s incredible route that led to the correct structure, thus securing it—it starts simply from a 7-bromoi-satin (128) (2004JA12888) It is ironic that with all the powerful physical... 

One interesting example that pertains to the use of the Davis variation is the synthesis of analogues of diazonamide A, cytotoxic ingredients of Diazona chinensis—and analogs of phorbazole A (a marine natural product) as reported by Liebscher et al. This report adds to the variation the ability to place non-aromatic substituents at C-1 (position 2) of the oxazole. The cyclization proceeds in the presence of 1.2 mol of Bp3 Et20, possibly used for the activation of the nitrile group to form the acylimidoyl chloride intermediate. 

The name azonazine was deduced from the fact that the structure contains both a part of diazonamide A, an alkaloid from the ascidiati Diazona chinensis (see Chapter 28) and a diketopierazine. 

The species Diazona chinensis, harvested in the Philippines in the upper part of an underwater cave, yielded diazonamides A and B, which are original bicyclic pep-tides with two isoxazoles, a chloroindole, and a fused indole/benzofuran system. X-ray analysis of diazonamide B p-bromobenzamide led to the exact structures, which were confirmed by total synthesis a decade later (Lindquist et al, 1991b Li et al, 2001). Diazonamide A is strongly cytotoxic in vitro to HCT-116 human colon cancer cells with an IC50 of 15 ngml . Diazonamide B is less active. Subsequently, diazonamides C-E were characterized in an imdetermined species of Diazona from Indonesia (Fernandez et al, 2008). 

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