采用逐步合成方法来制备叶酸的γ-共轭物：叶酸共轭灵菌红素是必要的。

Figliola Carlotta, Marchal Estelle, Groves Brandon R, Thompson Alison

Department of Chemistry, Dalhousie University PO Box 15000 Halifax NS, B3H 4R2 Canada

RSC Adv. 2019 May 7;9(25):14078-14092. doi: 10.1039/c9ra01435g.

Despite the vast literature that describes reacting folic acid with a pharmacophore, this route is ineffective in providing the correct regioisomer of the resulting conjugate. We herein present a step-wise route to the preparation of nine folate conjugates of the tripyrrolic prodigiosene skeleton. The strict requirement for step-wise construction of the folate core is demonstrated, so as to achieve conjugation at only the desired γ-carboxylic acid and thus maintain the α-carboxylic site for folate receptor (FRα) recognition. Linkages ethylenediamine, polyethylene glycol and glutathione are demonstrated.

尽管有大量文献描述了叶酸与药效团的反应，但该途径在提供所得缀合物的正确区域异构体方面无效。我们在此提出了一种制备三吡咯基灵菌红素骨架的九种叶酸缀合物的逐步路线。证明了对叶酸核心逐步构建的严格要求，以便仅在所需的γ-羧酸处实现缀合，从而保留α-羧基位点用于叶酸受体（FRα）识别。展示了乙二胺、聚乙二醇和谷胱甘肽的连接。