Fluorine‐Containing Chiral Drugs
Fluorine‐Containing Chiral Drugs
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DOI：
10.1002/9781118075647.ch5
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
X. Qiu;Xuyi Yue;F. Qing
中科院分区：
文献类型：
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作者：
X. Qiu;Xuyi Yue;F. Qing
氟是地球上最丰富的元素之一。然而，它在生物化合物中的出现是极其罕见的。到目前为止，在自然界中只发现了十几种含有氟原子的有机化合物。应该注意的是，所有这些天然存在的氟化化合物都只有一个氟原子（图5.1），其中两个[杀核素，（2 R，3R）-2-氟柠檬酸]含有一个直接连接到手性碳中心的氟原子[1]。尽管如此稀缺，有机化学家，药物化学家和药物化学家已经合成并广泛使用了大量的含氟化合物，因为将氟原子引入生物活性分子可以在其物理，化学和生物学性质上带来显着和深刻的变化[2]。在二十世纪的氟药物化学领域中，两个最著名的例子是9α-氟氢化可的松（抗炎药）[3]和5-氟尿嘧啶（抗癌药）[4]。在20世纪50年代，研究人员发现了这两种药物，其中仅向相应的天然产物中引入单个氟原子就带来了一些显着的药理学特性。到目前为止，美国FDA已经批准了一百多种含氟化合物用于治疗不同的疾病。2007年，全球最畅销的20种药物中有9种是含氟化合物或含氟化合物与其他化合物的混合物（图5.2）。例如，2007年最畅销和第三畅销的药物分别是立普妥和阿德麦
Fluorine is one of the most abundant elements on Earth. However, its occurrence is extremely rare in biological compounds. So far, only a dozen organic compounds containing the fluorine atom have been found in nature. It should be noted that all of these naturally occurring fluorinated compounds possess only one fluorine atom (Fig. 5.1), and two of them [nucleocidin,(2R, 3R)-2-fluorocitric acid] contain a fluorine atom that links directly to a chiral carbon center [1]. Despite such scarcity, organic chemists, medicinal chemists, and pharmaceutical chemists have synthesized and widely used enormous numbers of fluorine-containing compounds because the introduction of fluorine atom (s) into biologically active molecules can bring about remarkable and profound changes in their physical, chemical, and biological properties [2]. Two of the most notable examples in the field of fluoromedicinal chemistry in the twentieth century are 9α-fluorohydrocortisone (an anti-inflammatory drug)[3] and 5-fluorouracil (an anticancer drug)[4]. In the 1950s, researchers discovered both pharmaceuticals, in which the introduction of just a single fluorine atom to the corresponding natural products brought about some remarkable pharmacological properties. So far, over one hundred fluorine-containing compounds have been approved by the FDA in the United States for treating different diseases. In 2007, nine of the top 20 best-selling drugs worldwide were fluorine-containing compounds or mixtures of fluorine-containing compounds and other compounds (Fig. 5.2). For example, the best-selling and third-best-selling drugs in 2007 were Lipitor and Admair