| The shikimate pathway is a common biosynthetic pathway utilized by plants and microorganisms. Three kinds of aromatic amino acids (L-phenylalanine, L-tyrosine and L-tryptophan) are synthesised along this biosynthetic sequence. The pathway’s intermediates and the analogues, which contain a multifunctional hexanoid ring and three chiral carbon centers, can be transformed to derivatives which possess great potential pharmacological activities. And they had been widely applied in pharmaceutical industry, such as antivirus, antitumor, antimicrobial, antifungal, anti-inflammation and antithrombus. Here, we describe the syntheses of3-epi,4-epi and5-epi-shikimic acid from readily available and inexpensive shikimic acid.(1) Shikimic acid was transformed into halide111. In the presence of Vilsmeier-Haauc salt, halogenation of compound111gave112, which was then converted to113via an epoxidation reaction. Hydroxyl group of113was protected by acetyl groupto afford114. Compound115was obtained by ring-opening reaction of114. Then hydrolysis of115afforded the desired8.3-Epi-shikimic acid was obtained via6steps in71%overall yield from shikimic acid.(2) Compound113was protected by Bz to provide116. In the presence of CF3CO2H and HO Ac in CH2Cl2, ring opening of116gave compound117, which was then transformed to the corresponding118. The next step was regioselective deprotection of acetyl group of118to give119, which was converted to120via an epoxide-formation by NaH.121was obtained by ring opening of120. Then hydrolysis of121afforded the desired38.4-Epi-shikimic acid was accomplished by9steps in57%overall yield from shikimic acid.(3) Compound111was protected by2,2-DMP to afford108, then108was converted by methylsulfonation to give122. Selective deprotection of2,2-DMP afforded125. In the presence of tunable complex of R3N-R’COOH in toluene, SN2reaction was performed to give124. Then hydrolysis of124afforded the desired99.5-Epi-shikimic acid was produced over6steps in65%overall yield from shikimic acid. |
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