Synthesis Of 3-hydroxytetradecanoic Acid And Its S-enantiomer

3-hydroxytetradecanoic acid and its derivatives exist widely in the biological system. (R)-3-hydroxytetradecanoic acid is a natural component of lipid A which is the key component of endotoxin. Being incorporated into therapeutic agents featuring the structural motif of lipid A, its antipode (S)-3-hydroxytetradecanoic acid is reported to be able to enhance the immunoadjuvant activity inherent in lipid A. So the study of synthetic routes and technics of 3-hydroxytetradecanoic acid has both theoretical meaning and practice value.This research firstly studied the synthetic routes and technic of 3-hydroxytetradecanoic acid. Decyl chloride is used as starting material to prepare Grignard reagent. Region and chemoselective epoxide opening of epichlorohydrin with Grignard reagent gives 1-chloro-2-tridecanol which is used directly to react with sodium cyanide. Finally the product is hydrolyzed to give 3-hydroxytetradecanoic acid. During the Grignard reaction, decyl chloride is finally selected after comparing with 1-bromodecane because it could reduce the production of the byproduct eicosane significantly, also could be produced easier and cleaner. The mole ratio of epichlorohydrin and 1-decanol is finally determined to be 1:1 after optimization. In traditional techmics 1-chloro-2-tridecanol was reacted with sodium cyanide after epoxide formation which may generate virulent hydrocyanic acid. But in this research that step is omitted and more loss of product is also avoided. The overall yield of the product is 48.66%. The configuration of 3-hydroxytetradecanoic acid is identified by ~1H NMR and ESI mass spectrum, the melt point of the product is also measured.(S)-3-hydroxytetradecanoic acid is also prepared via asymmetric synthesis base on the similar route of the synthesis of 3-hydroxytetradecanoic acid. (S)-epichlorohydrin is used as the chiral pool. Since the reagent attacks in this route do not involve the chiral carbon atom, so the formation of S-enantiomer does not change theoretically. (S)-3-hydroxytetradecanoic acid is used to react with 2-chloro-4'-bromoacetophenone and 2-bromo-4'-chloroacetophenone separately togive derivatives which may could be detected by chiral column in HPLC. Butunfortunately the present equipments in the lab are not able to give the ee value of thederivatives. Further work is still needed.