醚脂类的合成:天然化合物及其类似物。
Synthesis of ether lipids: natural compounds and analogues.
作者信息
Gomes Marco Antônio G B, Bauduin Alicia, Le Roux Chloé, Fouinneteau Romain, Berthe Wilfried, Berchel Mathieu, Couthon Hélène, Jaffrès Paul-Alain
机构信息
Univ. Brest, CNRS, CEMCA UMR 6521, 6 Avenue Victor Le Gorgeu, 29238 Brest, France.
出版信息
Beilstein J Org Chem. 2023 Sep 8;19:1299-1369. doi: 10.3762/bjoc.19.96. eCollection 2023.
Ether lipids are compounds present in many living organisms including humans that feature an ether bond linkage at the -1 position of the glycerol. This class of lipids features singular structural roles and biological functions. Alkyl ether lipids and alkenyl ether lipids (also identified as plasmalogens) correspond to the two sub-classes of naturally occurring ether lipids. In 1979 the discovery of the structure of the platelet-activating factor (PAF) that belongs to the alkyl ether class of lipids increased the interest in these bioactive lipids and further promoted the synthesis of non-natural ether lipids that was initiated in the late 60's with the development of edelfosine (an anticancer drug). More recently, ohmline, a glyco glycero ether lipid that modulates selectively SK3 ion channels and reduces in vivo the occurrence of bone metastases, and other glyco glycero ether also identified as GAEL (glycosylated antitumor ether lipids) that exhibit promising anticancer properties renew the interest in this class of compounds. Indeed, ether lipid represent a new and promising class of compounds featuring the capacity to modulate selectively the activity of some membrane proteins or, for other compounds, feature antiproliferative properties via an original mechanism of action. The increasing interest in studying ether lipids for fundamental and applied researches invited to review the methodologies developed to prepare ether lipids. In this review we focus on the synthetic method used for the preparation of alkyl ether lipids either naturally occurring ether lipids (e.g., PAF) or synthetic derivatives that were developed to study their biological properties. The synthesis of neutral or charged ether lipids are reported with the aim to assemble in this review the most frequently used methodologies to prepare this specific class of compounds.
醚脂是存在于包括人类在内的许多生物中的化合物,其在甘油的-1位具有醚键连接。这类脂质具有独特的结构作用和生物学功能。烷基醚脂和烯基醚脂(也称为缩醛磷脂)是天然存在的醚脂的两个亚类。1979年,属于烷基醚类脂质的血小板活化因子(PAF)的结构被发现,这增加了人们对这些生物活性脂质的兴趣,并进一步推动了非天然醚脂的合成,这种合成始于60年代末依地福新(一种抗癌药物)的研发。最近,欧姆林(一种糖甘油醚脂,可选择性调节SK3离子通道并在体内减少骨转移的发生)以及其他也被称为GAEL(糖基化抗肿瘤醚脂)且具有有前景的抗癌特性的糖甘油醚,重新激发了人们对这类化合物的兴趣。事实上,醚脂是一类新的、有前景的化合物,具有选择性调节某些膜蛋白活性的能力,或者对于其他化合物而言,通过一种独特的作用机制具有抗增殖特性。对醚脂进行基础研究和应用研究的兴趣日益增加,促使人们对制备醚脂的方法进行综述。在这篇综述中,我们重点关注用于制备烷基醚脂的合成方法,这些烷基醚脂包括天然存在的醚脂(如PAF)或为研究其生物学特性而开发的合成衍生物。本文报道了中性或带电醚脂的合成,目的是在这篇综述中汇总制备这类特定化合物最常用的方法。