Synthesis N-Perfluoroalkylethyl-substituted Oxadiazole, Triazole And Its Application Of Quasiracemic Synthesis

Recently, fluorinated functional compounds have been gained to chemist's attentions since it was found that the introduction of fluorine atoms or fluorous alkyl into organic molecules could lead to significant changes in biological activities. It has been reported that 1,3,4-oxadiazole and 1,2,4-triazole derivatives having substituted aryl group, such as the 5-substituted phenyl group or a 3,5-disubstituted aryl group, exhibit bactericidal, antiinflammatory, tuberculostatic, anticonvulsion, and fungicidal activities. There a few papers reported the reactivity of the hydrogen of NH group in heterocycle, for example, Mannich base reaction. However, the same hydrogen substituted by perfluoroalkyl is not reported in the literature. Compound 3 was synthesized by reaction of acid chloride with amino acid ester in the presence of Et3N and DMF. After several steps synthesizing, the 1,3,4-oxadiazole-2-thiones(2-5) and 1,2,4-triazole-5-thiones(2-8) were obtained. Combining the oxadiazole and triazole with good activities, two series of N-2-perfluoroalkylethyl-substituted 1,3,4-oxadiazole-2-thiones(2-6a ~ 2-6l) and 1,2,4-triazole-5-thiones(2-9a ~ 2-9l) were synthesized in the second chapter this paper and their structures were confirmed by 1H-NMR, 19F-NMR, IR, mass spectra and elemental analysis. The experimental results and the calculation showed that the hydrogen of NH group in heterocycle was more active than the hydrogen on CONH to finish alkyl-substitution reaction on nitrogen through the computing module Dmol3 of Materials Studio 3.0. Some compounds biological activities are testing.Chiral compounds abound in organic, medicinal, and natural products chemistry. Today, there are two ways to make enantiopure (or enantioenriched) organic molecules: racemic synthesis followed by resolution, or asymmetric synthesis. The third chapter in this paper introduces herein a third method, quasiracemic synthesis.Classical racemic synthesis makes both enantiomers of a target compound in a single synthesis, but separation (resolution) and identification of the final enantiomers pose large hurdles. Asymmetric synthesis employs enantiopure compounds, but two separate syntheses are needed if both enantiomers are desired. quasiracemic synthesis unites some of the key advantages of racemic and asymmetric synthesis. However, given two enantiomers with high application, especially, the R- and S- configuration products must studied their biological, chemical properties respectively. Therefore, two series assymetrically synthesis are carried out in order to obtain R- and S- configuration products. It is obviously that the method for original research is a very complicated and difficult when only relying on asymmetric synthesis. Like asymmetric synthesis, quasiracemic synthesis starts and finishes with enantiopure compounds, but like racemic synthesis it provides both enantiomers in a single synthesis."Quasienantiomers"are used in place of enantiomers, and the separation and identification of the final quasienantiomers is ensured by a tagging strategy.The third chapter in the present paper using 4-iodine benzoic acid as starting material, two N-perfluoroalkyl-4-phenyl-3-(4-iodinephenyl)-1,2,4-triazole-5-thione are synthesized, the fluorous tagging is C6F13 and C8F17, respectively. The amide are obtained reacts D, L-configuration of the alanine ester with 4-iodinebenzoyl chloride. Two 4-acetylene alaninemethylesters are synthesized after deprotection compounds 3-9 which using the iodine atom on the benzene ring coupled with trimethyl silicon alkyl acetylene. Again Sonogashira coupling are happened between L-configuration 4-acetylene benzamidoalanine methylesters with N-perfluoroalkyl 1,2,4-triazole- 5-thione which the fluorous tagging is C6F13. In similarly, the D-configuration is coupled with triazole which the fluorous tagging is C8F17. Both two products are equal to mix and gain Quasienantiomers. After hydrazide and cyclization, the 2-methly-4-(4-N-perfluoroalkyl-4-phenyl-1,2,4-triazole-5-thione-phenyl)acetylenebenzamido-1,3,4-oxadiazoline-thione are synthesized. Lastely, two enantiopure are obtained after demix.The forth chapter in the present paper focuses on the synthesis of Schiff-base, in other words, the research is the continuation of the second and third research works. The different biological activity functional group to gather in the identical molecule can realize the active superimposition and develop newly highly-efficient heterocyclic compounds with broad-spectrum activity. Accordingly, the 1,2,4-triazole-5-thione Schiff bases are synthesized by some different substituted aromatic aldehydes react with 1,2,4-triazole. Then, the hydrogen of NH group in heterocycle is substituted by perfluoroalkyl and tetraethyl acyl-glucose, respectively. Based on the activity superposition principle, the compounds with more potential biological activities are hoped to obtain.Sugar modification can decrease the toxicity and increase absorption of some nature drugs. Nowadays, synthesis of sugar compounds to modify nature drugs has become an important field of pharmaceutical chemistry. Retinoids play an essential role in vertebrate growth and development, supporting cell differentiation; embryonic development, vision, the immune response and reproduction. Retinoids has been found to be too toxic at high dosage levels to be of practical value for cancer prevention in higher mammals. In order to enhance pharmacal effects and gain the relative derivatives with better curing effect and selectivity, structures of retinoic acids were modified by inducing glycosyl groups in this paper. Nine glucuronide conjugates of 13-cis-retinoic acid acid were synthesized in two ways and not reported in literatures until now. A new retinoylation method using of DCC as reagent under catalysis DMAP was developed after evaluated various reaction conditions. The O-glycosylation method was investigated using of DMAP as phase-transfer catalyst. Furthermore, deacetylation of glycosyl retinoates was studied using catalytic amount of dibutyltin oxide as catalyst in methanol. Finally all compounds were determined in vitro by MTT assay using human cancer lines including A549 cells lines etc. Results showed that glucoside derivatives exhibited interesting cytotoxic activities and were stronger than glycosyl esters. Deactylation of 5-3 and 5-11 also improved their bioactivities than those 5-2a and 5-9a, respectively.