从廉价的天然d-半乳糖和d-葡萄糖出发，实现了一条高选择性、高效和简便的合成新型生化活性的糖融合吡喃并[3,2-c]吡喃酮衍生物的途径。首先，通过6步将这些d-六元糖合成β- C-糖基糖醛，总产率为41-55%。接下来，通过碱性条件处理这些β- C-糖基糖醛，合成了两种不同的1- C-甲酰基甘露糖，并进行了反应条件优化，采用1- C-甲酰基甘露糖与4-羟基香豆素之间的反应。接着，在乙酸乙酯中，在室温下（25°C）并加入l-脯氨酸的条件下，将1- C-甲酰基甘露糖和1- C-甲酰基葡萄糖分别与九种不同的取代的4-羟基香豆素处理约1-2小时，以优异的收率纯度获得单一对映异构体的吡喃并[3,2-c]吡喃酮衍生物。其中四个化合物显示出对MCF-7乳腺癌细胞系的活性。MTT抗癌试验、凋亡试验和迁移分析显示合成化合物引发的癌细胞的显著死亡。本文由《化学学会》所有。

A highly stereoselective, efficient and facile route was achieved for the synthesis of novel and biochemically potent sugar fused pyrano[3,2-c]pyranone derivatives starting from inexpensive, naturally occurring d-galactose and d-glucose. First, β-C-glycopyranosyl aldehydes were synthesized from these d-hexose sugars in six steps, with overall yields 41-55%. Next, two different 1-C-formyl glycals were synthesized from these β-C-glycopyranosyl aldehydes by treatment in basic conditions. The optimization of reaction conditions was carried out following reactions between 1-C-formyl galactal and 4-hydroxycoumarin. Next, 1-C-formyl galactal and 1-C-formyl glucal were treated with nine substituted 4-hydroxy coumarins at room temperature (25 °C) in ethyl acetate for ∼1-2 h in the presence of l-proline to obtain exclusively single diastereomers of pyrano[3,2-c]pyranone derivatives in excellent yields. Four compounds were found to be active for the MCF-7 cancer cell line. The MTT assay, apoptosis assay and migration analysis showed significant death of the cancer cells induced by the synthesized compounds.This journal is © The Royal Society of Chemistry.