Methyl 12 -HETE

Corey has developed a method to resolve the ( )-5-HETE methyl ester enantiomers using the isocyanate of dehydroabietylamine 32 to form diastereomeric carbamates 33a-33b (Scheme 2.13). Separation of the diastereomers was achieved by column chromatography and the free alcohol was regenerated using trichlorosilane. The two examples given above constitute chemical resolution using external agents. 

The naturally occurring isomer of 5-HETE has the (S)-configuration at C-5. Corey and Hashimoto have reported the chemical resolution of ( )-5-HETE methyl ester as discussed in Section 2, Scheme 2.13... 

Unfortunately, attempts to synthesize the optically active 5-HPETEs by displacement of the mesylates of (5S)- or (57 )-HETE methyl ester with hydrogen peroxide resulted in racemization and formation of ( )-5-HPETE. 

The 6-lactone (359) was prepared by iodo1 act onization of arachidonic acid and converted into ( )-5-HETE methyl ester (360) (Scheme 52). Mesylation of this ester followed by reaction with... 

In these experiments I5S-HETE methyl ester was used os a substrate. 

The method was used for attachment of the cis enyne side chain in a synthesis of gephyrotoxin, and for the preparation of (Z)-non-3-en- 1-yne, a building block in the synthesis of prostaglandins and of 11-HETE methyl ester. ... 

Good Z-selectivities were observed for the reaction of aldehydes with carboxy ylides prepared from the corresponding phosphonium salt and LHMDS. This strategy has been extensively used in the total synthesis of prostaglandins, monohydroxy-eicosatetraenoic acids (HETE), and leukotrienes. Eor instance, the Wittig condensation between aldehyde 5 and car-boxy phosphonium salt 6 in the presence of LHMDS provided 49% yield of the TBDPS-protected 10(5)-HETE methyl ester 7 (eq42). ... 

Acyclic ( 7 -pentadienyl)iron cations have been used to stereochemically control G-G bond formation in the syntheses of numerous types of products. This methodology has been used in the synthesis of (i )-5-HETE methyl... 

A number of natural products or fragments of them have become available by nucleophilic additions to the aldehyde group of tricarbonyl(T -dienal)iron complexes. This includes ( )-5-hydroxy-6 , 8Z,l lZ,14Z-icosatetraenoic acid (5-HETE) methyl ester,(-)-LTA4 methyl ester, halicholactone, racemic lipoic acid methyl ester,macrolactin A fragments, the as-indacene unit of ikarugamycin, 1 l-(Z)-retinal, and the C11-C17 segment of soraphen Asymmetric variations... 

These GC conditions are suitable for analyzing many prostaglandins, thromboxanes, leuko-trienes, and other metabolites of arachidonic acid, such as the hydroxyeicosatetraenoic (HETE) acids. However, the 5-, 12-, and 15-HETE isomers are difficult to separate using GC methods. Sometimes the methyl ester-TMS derivatives provide a better GC separation, or for ketoprostaglandins, the MO-methyl ester-TMS derivatives often give a better separation... 

Additional hypotheses concerning prostaglandin biosynthesis in P. homomalla resulted from isolation of 11R-HETE (76) from the polar lipid fraction [95]. Apparently, 11R-HETE (76) is also a minor product of incubations of arachidonic acid with acetone powder preparations of P. homomalla [95], In this alternate hypothesis (Scheme 8), an 11-hydroxy or 11-hydroperoxy-8,9-allene oxide intermediate is formed from a sequence of oxidations at C8 and Cll. Opening of the allene oxide to a transient C8 earboeation induces eycli-zation with a consequent addition of water to C15. This proposed pathway leads initially to formation of PGE2 (16 or 38), which following acetylation, elimination of acetic acid from Cl 1-12, and esterification, forms the observed major natural product in the coral, 15-acetoxy methyl PGA2 (36 or 54). Notably, if... 

Another barnacle species, Elminius modestus, was found to produce mono and trihydroxy fatty acids [146]. Analysis of the extract of whole animal homogenates by TLC provided two hatching factor active bands. The more polar band was tentatively identified as a trihydroxy fatty acid (THFA) band. The less polar band had an / r value similar to a 5-HETE standard. The compounds from this latter band were eluted from the TLC plate, methylated, and trimethylsilylated. GC-MS analysis detected several HEPE s and small amounts of monohydroxy derivatives of Ci8 1, C18 2, and C22 fatty acids. Hydrogenation and subsequent GC-MS analysis allowed identification of the major compound as 8-HEPE (ca. 70%). Five to ten percent of 9-, 11-, and 15-HEPE and minor amounts of 5-, 6-, 12-, and 13-HEPE were also detected. No stereochemical features of these oxylipins were determined. 

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