HETEs

Detailed accounts of the biosynthesis of the prostanoids have been pubUshed (14—17). Under normal circumstances arachidonic acid (AA) is the most abundant C-20 fatty acid m vivo (18—21) which accounts for the predominance of the prostanoids containing two double bonds eg, PGE2 (see Fig. 1). Prostanoids of the one and three series are biosynthesized from dihomo-S-linolenic and eicosapentaenoic acids, respectively. Concentrations ia human tissue of the one-series precursor, dihomo-S-linolenic acid, are about one-fourth those of AA (22) and the presence of PGE has been noted ia a variety of tissues (23). The biosynthesis of the two-series prostaglandins from AA is shown ia Eigure 1. These reactions make up a portion of what is known as the arachidonic acid cascade. Other Hpid products of the cascade iaclude the leukotrienes, lipoxins, and the hydroxyeicosatetraenoic acids (HETEs). Collectively, these substances are termed eicosanoids. 

Lipoxygenation is the major pathway of dioxygenation of arachidonic acid in blood platelets and leads to the 12-5-hydroperoxy acid 12-HPETE and the corresponding 12-hydroxy acid 12-HETE. Several pathways for the synthesis of 12-HETE have been developed. However, despite the availability of this substance, its biological role remains undetermined. 

HETE was also obtained together with ( )-ll-HETE via the epoxide opening reaction of 11,12-epoxyarachidonic acid (Ref. 4). 

Synthesis of 5-, 11-, and 15-HETE s. Conversion of HETE s into the Corresponding HPETE s... 

The first step in the biosynthesis of eicosanoids from arachidonic acid is generally a lipoxygenation reaction. The resulting hydroperoxides (HPETE s) can undergo reduction to the corresponding alcohols (HETE s). Preparative routes to the 5-, 11-, and 15-HETE s and HPETE s have been developed as oudine below. 

Optically pure 5-HETE can be made in quantity by resolution of racemic 5-HETE (Ref. 2). 

Each HETE can be converted into the corresponding HPETE as shown in the following example. 

J Hete ootomct p otes 0 M i a-Hete Ootomolkylct p Otes... 

W j J Hete OotO -ncfAp Otei onrf a-Hete DatomolkyhiAp Otes O O VC iy thesls R OAc... 

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