5,6-Dehydroarachidonic acid

Dehydroarachidonic acid analogs in which one Z-olefinic unit is replaced by a triple bond are irreversible inhibitors of the lipoxygenasses which normally deliver dioxygen to the corresponding site of arachidonic acid. The inactivation appears to be a consequence of dioxygenation at the acetylinic unit to from a vinyl hydroperoxide which undergoes rapid 0-0 homolysis. Synthetic routes to these interesting enzyme inhibitors are outlined below. 

A neat combination of some of the foregoing chemistiy is use of the cyclic stannane (48) as an equivalent of the 1,4-pentadienyl dianion (49). Thus, treatment of the stannane (48) with Bu"Li, copper(I) iodide-dimethyl sulfide complex and the iodoallene (50) smoothly leads to the dienyne (51) and thence, by a repetition of this sequence but using electrophile (52), to 3-dehydroarachidonic acid methyl ester (53). 

Fig. 39. Mechanism proposed for inactivation of IS-lipoxygenase by l4,IS-dehydroarachidonic acid.

Corey and Kang have developed the coupling of vinylcopper reagents with iodoallenes to enynes, providing useful syntheses of 5,6-, 11,12-, and 8,9-dehydroarachidonic acids.For example, addition of the cuprate that is generated from the vinylstannane (319) to the iodo-allene (320) furnishes 11,12-... 

A biomimetic route from arachidonic acid to leukotrienes C, D, and E is reported. During a short stereocontrolled synthesis of three dehydroarachidonic acids the metallocycle (53) undergoes lithium-tin transmetallation to give (54), which is converted into (55) with masterful control and simplicity (Scheme 26). ... 

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