Using the presently synthesized amide analogue of chlorogenic acid as a starting material, it will be possible to synthesize more stable derivatives. hepatic glucose-6-phosphate translocase [9,10,11]. This enzyme catalyzes the final step in glycogenolytic and gluconeogenic pathways to liberate free glucose into the circulation, and inhibitors of this enzyme are potentially good for diabetic patients. Introducing a lipophilic chain and an amino acid residue to position 7 of chlorogenic acid led to potent anti-fungal compounds [12]. Adding lipophilic chains through acetal/ketal bonds to chlorogenic acid resulted in potent Cglucosidase dMCL1-2 inhibitors [13]. -Glucosidase inhibitors could slow down the digestion and absorption of carbohydrates and thus are beneficial to type II diabetes patients. Because of the important roles of this compound in human health, scientists have been making much effort to find and improve the synthesis method of chlorogenic acid. dMCL1-2 However, as there are several hydroxyl groups, a carboxyl, and an ester group in the structure, the task is quite difficult. In 2001, Sefkow reported the synthesis in higher yield of a quinic acid bisacetonide (1, structure shown in Scheme 1), in which the 1-OH, 1-COOH and 4,5-OH were protected and only 3-OH was free, and efficiently synthesized chlorogenic acid by reacting 1 with acetylcaffeoyl chloride followed by de-protection [14]. It was observed that, although a small a part of chlorogenic acid could be assimilated quickly, a large part of this compound was hydrolyzed through breakage of the ester bond between the caffeic and dMCL1-2 quinic acid moieties [15,16,17]. It is known that some bioactivity of chlorogenic Rabbit polyclonal to Wee1 acid could be lost if the ester bond was broken, such as in the case for the inhibition of hepatic glucose-6-phosphate translocase, chlorogenic acid showing good activity while neither caffeic acid nor quinic acid was active [9]. It is well documented that amides are more stable to esterase hydrolysis than esters, and if the ester bond of a compound was replaced by an amide bond, the stability would improve significantly [17,18]. Oxidative stress caused by reactive species of oxygen (ROS) damages cellular components and is recognized as one of the causes of chronic disease [19,20]. Human hepatoma cell line HepG2 is a reliable model dMCL1-2 for biochemical studies of intracellular antioxidant [21]. The present study aimed to synthesize and test the intracellular antioxidant activity of a chlorogenic acid analogue with an amide bond instead of the ester bond. In addition, the stability, anti-HCV activity, and toxicity on brine shrimps of this compound are described and compared with chlorogenic acid. 2. Results and Discussion 2.1. Synthesis of 5-Caffeoylquinic Acid Amide The first step was to synthesize 3-amino-3-deoxy-quinic acid. Due to the multiple hydroxyl groups in the structure of quinic acid, it is difficult to pressure the reaction to occur in the desired position. The authors of [14] solved this problem by synthesis of compound 1. The present research investigated the method to convert the hydroxyl group to amino group as described in detail in the following passage. The desired product was obtained by acylation of the amino intermediate and finally de-protection. As both acid sensitive (4,5-ketal) and alkaline sensitive (7-ester) groups exist in the structure of 1 1, reactions were carried out in conditions as dMCL1-2 mild as you possibly can. The synthesis route for the chlorogenic acid analogue from compound 1 [14] was depicted in Scheme 1. Compound 1 was firstly oxidized with pyridinium dichromate to give the ketone compound (2), which was then converted to the hydroxyimino compound (3) through reaction with NH2OHHCl..