甘草酸(glycyrrhizin)(GZ)，是由甘草次酸(glycyrrhetic acid)(GA)與兩分子的葡萄糖酸所組成的，為甘草屬植物(Glycyrriza sp.)主要成分及生物活性化合物，其藥理活性包括：抗發炎，抗潰瘍，抗氧化，抗腫瘤，抗病毒及做為解毒劑。
　　甘草次酸(GA)，是天然藥物資源的先導藥物，用於病毒性肝炎及HIV病毒的治療。而甘草酸的monoammonium salt(glycyram, tussilinar) 已是醫療用藥，主要用於治療發炎及抗過敏藥。
　　基於甘草酸擁有多項的生物活性，於本研究將利用當做半合成的起始物且以簡單的取代反應於C-3位置上的官能基修飾，來合成甘草次酸衍生物，並將所得的衍生物做為抗病毒及抗腫瘤活性測試。到目前已完成29個衍生物。
　　首先是利用甲醇在硫酸存在下將GZ水解並甲酯化得到甲基甘草次酸酯GLY，再利用Jones reagent氧化C-3位置上二級醇形成酮基GLY-A，然後與NH2OH縮合成肟(oxime) GLY-B，GLY-B與NaH和二溴長直碳鏈(n=4,5,6)形成GLY-Cn，利用GLY-Cn與雜環的試劑做取代反應，如：morpholine，thiomorphline，piperazine，得到GLY-Fn，GLY-Gn，GLY-Hn(n=4,5,6)；及利用核酸如：腺嘌呤(adenine)，尿嘧啶(uracil)，胸腺嘧啶(thymine)等雜環取代GLY-Cn長直鏈的另一端，得到GLY-Dn，GLY-In，GLY-Jn(n=4,5,6)。最後利用GLY-B與GLY-Cn縮合形成GLY-En(n=4,5,6)。
　　所合成的甘草次酸衍生物，皆已送測藥理活性中。

　Glycyrrhizin(GZ), a diglycoside of glycyrrhetic acid(GA) is a major and active constituent of the root of Glycyrriza sp.(licorice) which is the most commonly used herb in traditional Chinese medicine. GZ possesses a broad spectrum of
Pharmacological effects including anti-flammatory, anti-ulcer, anti-dote, anti-oxidant, anti-tumor, anti-viral and so on.
　GA is one of the leading natural compounds for clinical trials of chronic active viral, hepatitis and HIV infections. Its monoammonium salt(glycyram, tussilinar) is used as an anti-inflammatory and anti-allergic remedy.
　Due to multiple protective actions of GZ, the present study is aimed to prepare its semisynthetic derivatives via functional group modifications at C-3 site followed by synthesis of dimers for studies of antiviral and anti-tumor activities. As a result, synthesis of 29 analogues has been accomplished.
　Glycyrrhetic acid methyl ester (GLY) is prepared from GZ on hydrolysis and esterifcation with and methanol in the presence of H2SO4. The hydroxyl group at C-3 is oxidized into carbonyl group (GLY-A) with CrO3 in the presence of CH3COOH(Jones reagent) and THF. In the next step GLY-A is converted into its oxime (GLY-B) with NH2OH in THF. The long chains with n=4, 5, and 6 are introduced on C-3 oxime by NaH and THF to give GLY-Cn. Substitution of heterocyclic compounds like morpholine , thiomorpholine and piperazin on the other end of long chain derivatives (GLY-Cn) in the presence of NaH and THF is given GLY-Fn, GLY-Gn and GLY-Hn(n=4, 5, 6). Similary, nucleotides like adenine, uracil, thymine are attached on the other end of long cheain derivatives by the condensation between GLY-Cn in the presence of K2CO3 and DMF to afford GLY-Dn, GLY-In, GLY-Jn(n=4, 5, 6). In the last part, synthesis of dimer composed of GLY-Cn and GLY-B in the presence of NaH and THF to give GLY-En(n=4, 5, 6).
　Currently, the bioactivity studies of these synthesized analogues are in progress.

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