| Cytochrome P-450 metabolites, including the epoxyeicosatrienoic acids (EETs) which play an important role in the system of heart vein. In the recent years, a 14,15-EET analogue, (14,15)-epoxyeicosa-5(Z)-enoic acid (14,15-EE-5-ZE) was synthesized and identified as an EET-specific antagonist. In our work, we designed and researched the synthesis route of a key intermediate (5,14)-eicosadiyne-1-tetrahydropyran and synthesized it.1,7-heptadiol, the starting material, reacted with hydrobromic acid to produce 7-bromheptane-1-ol, which hydroxy was protected by 2,3-dihydropyran . Then, it coupled with the heptaalkyne. The coupling product was taken off the 2,3-dihydropyran at the extremity, and the alcohol we obtained was brominated with CBr4 and PPh3, furnishing a new bromide (a). Next, the hydroxy of 5-hexyne-1-ol was protected by 2,3-dihydropyran with the catalytic reaction of PPTs. Alkylation of the protected alkyne, using bromide (a), produced the bis-acetylene. The total yield was 14.5%.Some innovations we did as following: firstly, we designed a new synthesis route of (5,14)-eicosadiyne-1-tetrahydropyran; secondly, we studied the bromination reaction influence factors of 1,7-heptadiol in detail, including reaction time,reaction temperature,solvent dosage,reagent mole ratio; thirdly, we discussed the mechanism of 1-alkyne coupled with mono-bromide, and optimized the reaction condition.We utilized silica gel column chromatography to separate and purify product, and applied infrared spectrum,1H NMR and mass spectrum to testify product structure. The final result indicated that our synthesis route was feasible.
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