Synthesis domoic acid

The synthesis of kalnlc acid, acromehc acid, and related compounds such as domoic acid has been the subject of considerable investigation A simple and direct toiue to neurophysi-ologically active kalnlc acid analogs has been reported, as shovm in Scheme 10 31 ... 

Ohfune Y, Tomita M (1982) Total Synthesis of (—)-Domoic acid. A Revision of the Original Structure. J Am Chem Soc 104 3511... 

Domoic acid 4 (Figure 3) was isolated in 1958 from another Japanese marine alga, Chondria armata.4 Determination of the stereochemistry at C-5 proved problematic until it was confirmed as R by Ohfune in a total synthesis achieved in 1982.5 Structurally related derivatives, isodomoic acids A-F and domoilactones A and B have subsequently been isolated from Chondria armata. 

In a similar manner, these researchers have also synthesized [48] a C-8 side-chain analog 60 of domoic acid using a cobalt-mediated cyclization-elimination sequence on the iodide 59 (Scheme 22). They extended this methodology to an enantiospecific total synthesis of acromelic acid A 64, a potent neurotoxin obtained from poisonous mushrooms [46]. The cornerstone of their synthetic strategy was a cobalt-mediated radical cyclization of the substrate 61 which was prepared from the epoxy alcohol in optically pure form. Treatment of 61 with cobalt(I) afforded 62, which was converted to the natural product 64 via pyridone 63 using routine functional group manipulation (Scheme 23). 

Scheme 22. Cobalt-mediated synthesis of C-8 side-chain analog of domoic acid...

A revised structure for the unsaturated triacid natural product (—)-domoic acid has been established by A"-ray crystallographic analysis during a total synthesis of the molecule. ... 

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