Study On Synthesis Of (5Z, 14Z)-gadoleyl-1-ol

In this paper, we overviewed the epoxyeicosatrienoic acid(EETs) and its analogue-14, 15-epoxyeicosa-5(Z)-enoic acid(14,15-EE-5-ZE) recent status. The total synthesis of 14, 15-EE-5-ZE was primarily explored. A new stereoselective synthesis route of the key intermediate -(5Z,14Z)-gadoleyl-1-ol was designed and researched.In this work , 1,8-octodiol, the starting material, reacted with 40% hydrobromic acid to produce 8-bromooctan-1-ol, with the catalytic action of PPTs, its hydroxyl group was protected by 2,3-dihydropyran. Then it coupled with 1-heptaalkyne, by means of P-2 nickel as catalyst, stereoselectivity catalysis hydrogenated, with the catalytic action of acid to take off extremital 2, 3-dihydropyran which protected hydroxy group, then used PCC to oxidize alcohol into corresponding aldehyde(a). 1,5-Pentanediol reacted with phosphorus tribromide to make it mono-bromination, under the catalytic action of PPTs it reacted with 2,3-dihydropyran to protect another hydroxy group, then to react with triphosphine, produced quarterphossal(b). (a) with (b) under strong base butyl Lithium, Wittig reaction was carried out, after cast off extremital 2,3-dihydropyran which protected hydroxy group, then 5(Z),14(Z)-gadoleyl-1-ol was obtained. Total yield was 3.4%.The main work we did on synthesis: We studied bromination reaction influence factor in detail, such as reaction time,reaction temperature,solvent dosage,reagent mole ratio, and optimized the reaction condition, discussed reaction mechanism rudimentally. We optimized reaction condition and discussed the mechanism of 1-heptaalkyne coupled with mono-bromide. We improved on the technique of preparation P-2 nickel catalyst. We explored and discussed the reaction condition of other reactions. During experiment we applied thin-layer chromatography to grope the separating condition of product, utilized silica gel column chromatography to separate and purify product, and applied infrared spectrum, 13C NMR, mass spectrum to testify product structure. Result indicated this route of synthesis possess mild reaction conditions, a higher stereoselectivity. Synthetic route was feasible.