Studies On The Synthesis Of Polyunsaturated Acid-Heterocycle Derivatives

Polyunsaturated fatty acid is a type of compound with long-chain hydrophobic structure containing one or more separated double bonds. Most of them have significant bioactivity that is relative to man's physiological function, such as antineoplastic agents, lower blood pressure and blood fat, anti-inflammatory, anti-oxidant, immunoregulation and so on. Up to date, some of the polyunsaturated fatty acids derived products have been applied to the aspect of medicine, supplementary and health-care food. The purpose of this thesis is to design and synthesize a series of saturated and polyunsaturated long chain fatty acids derived heterocyclic conjugates and screen out prodrug molecules with potential applied value, by the modification of the known capecitabine and sugar-thiourea substituted indazole derivatives, respectively. The specific work are as follows:1. The mono-long chain carbonyl substituted capecitabine la-6a and double-long chain carbonyl substituted capecitabine lb-6b were synthesized via condensation of the relative fatty acid and the capecitabine molecule at low tempreture. The structures of the synthesized new molecules were characterized by IR, NMR and HRMS and the effects of the ratio of fatty acid and capecitabine on the substitution degree, the loading of catalyst and condensation agents were studied. 2. In the second part of the thesis,2,3,4,6-tetra-acetyl-β-D-glucopyranosyl isothiocyanate was firstly synthesized from D-glucose in a three-step procedure including acetylation, bromination, NCS-substitution. Then,2,3,4,6-tetra-acetyl-β-D-glucopyranosyl thioureas 7 was prepared using 5-amino indazole and the above product at room temperature. Finally, a series of novel conjugates 8a-12a and 8b-12b were synthesized by the condensation of thiourea 7 and the relative fatty acid. Furthermore, the condition for the deacetylation of the product were also studied.