| 3-Palmityloxy Shikimic acid, 3-PSA is a new chemical entity; it is a lipid-soluble derivative of shikimic acid. Shikimic acid, Shikimic acid, is a natural product with bioactivity extracted from the fruit of lllicium verum Hook. f (Magnoliaceae). It is the material to synthesis of Tamiflu which is the only effective medicine against H5N1 avian influenza while it is also has anti-thrombosis activity and can relieve brain damage after ischemia-reperfusion, Comparing with shikimic acid. 3-PSA maintains chirality of three hydroxyl wholly and selectively protect 3-hydroxyl, which is essential to shikimic acid usage in chiral drug synthesis. For example, drug against H5N1 avian influenza influences on neuraminidase. Its natural substrate sialic acid (2-deoxy-N-acetylneuraminic acid) maintains spatial configuration of 3-hydroxyl and convert spatial configuration of 4-hydroxyl and 5-hydroxyl. The product of selectively acylation of shikimic acid 3-hydroxyl with a series of fatty acid can be material to synthesize Tamiflu analogue. As a method, it also offers an one-step synthesis to protect shikimic acid which helps Shikimic acid as material to synthesize other bioactive substance.3-PSA may have similar activity to shikimic acid while acylation of shikimic acid optimize the lipid/water partition. Above all, selectively protection 3-hydroxyl is important to its usage in chiral drug synthesis and shikimic acid activity improves.In this paper, firstly, a new TLC system, including mobile phase system and coloration method, is setteled up to analyze shikimic acid and its acylating derivatives due to the help of HPLC-MS.With this analusis method,the investigation researches on enzyme catalyzed acylation of shikimic acid, confirming that Novozym 435 can selectively acylated hydroxyl of shikimic acid without influence on carboxyl. Contrast to chemical catalyst sulfuric acid which leads to polymerization of shikimic acid and dichloral sulfide which lead to racemization, Novozym 435 will not induce these side reaction. Considering two acylation reagent, acetic anhydride and vinyl acetate have too strong acylating activity to show the activity of Novozym 435. In the investigation of Novozym 435 activity to shikimic acid, enzyme shows the activity of selectively acylated 3-hydroxyl which only one kind of monoacylating product is synthesized. We purify the product by silica gel column and identify its structure to be 3-Palmityloxy Shikimic acid. This also validate Novozym 435 can selectively acylated 3-hydroxyl. Because though this method, water produced by the reaction can not be removed limits percent conversion and burdened the purification, so a new technics which can remove the water produced is developed and synthesis scale is improved to 10 gram level. The solvent Tert-amyl alcohol mixed with water can form minimum boiling point azeotrope, reduced pressure distillation and adding Tert-amyl alcohol though the reaction procedure can move the water from reaction system consistently and raise shikimic acid percent conversion to 95% if shikimic acid react and palmitic acid in the proportion of 1:1.24. According to this synthetical method, a new purification way is developed to avoid silica gel column which has limited quantity and serious pollution.At last, we expand the usage of this kind of reaction. Saturated fatty acid, including lauric acid, myristic acid, stearic acid and arachic acid; unsaturated fatty acid, including oleic acid, linoleic acid, zoomaric acid, all these can react like palmitic acid catalyzed by Novozym 435. Besides, methyl palmitate can replace palmitic acid in reaction.
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