5-HETE methyl ester, synthesis

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). ... 

Resolution of alcohols (c/., l-(naphthyl)ethyl isocyanate, 8, 356-357). A practical synthesis of the methyl ester of (S)-5-HETE (1) from arachidonic acid involves chromatographic separation of the diastereomeric urethanes prepared" from the isocyanate derived from dehydroabietylamine (hydrogen chloride and phosgene).1 Urethanes from other chiral amines are less useful. The urethanes are cleaved with triethylamine and trichlorosilane to give the corresponding pure enantiomeric esters, which can be hydrolyzed by base. 

The (S)-isomer of the title compound has been used as a synthon in all but one of the reported syntheses of LTB4 as well as the synthesis of LTBx and a synthesis of (5/ )- and (5S)-HETE, as discussed above in Section 3.A.2. Corey s group has described two syntheses of the methyl ester (S) 21a, both starting from 2-deoxy-D-ribose. In path (Scheme 3.7), 2-deoxy-D-ribose was first protected as the acetonide, which was transformed to the epoxide 18. The latter was also obtained in a second synthesis (path B), which bypassed the initial protection of 2-deoxy-D-ribose as an acetonide. 

Just and Luthe have recently reported the synthesis of the racemic methyl ester of 11-HETE, starting from a derivative of glycidol (Scheme 4.5). Since optically active glycidol is available, they point out that their synthesis could also be applied to obtain the natural (7 )-isomer. They found that the ketal blocking... 

In the following years, epoxy ester 89a was used as a key starting material for the synthesis of a number of metabolites of arachidonic acid (8) and analogs. Of particular interest is Corey s synthesis of ( )-l 1-HETE (92), ( )-12-HETE (25), ( )-15-HETE (26), and their corresponding peroxides published in 1980 [76]. ( )-15-HETE (26) was obtained in 70% yield in one step by reaction of the corresponding acid 89b of epoxy methyl ester 89a with excess of isopropyl cyclo-hexylamine and ethylmagnesium bromide (Scheme 3.24). 

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