甘露糖赤藓糖醇脂质 (MEL) 是一类带有亲水性 4-O-β-D-吡喃甘露糖基-D-赤藓糖醇骨架的两亲性分子。在这里，我们设计并合成了四种MEL类似物R-MEL-A（[2R,3S]-赤藓醇型）、S-甘露糖苏糖醇脂质（MTL）-A（[2S,3S]-苏糖醇型）、R-MTL -A（[2R,3R]-苏糖醇型）和α-S-MEL-A（[2S,3R]-赤藓糖醇型）使用我们之前报道的硼介导的苷元递送（BMAD）方法和邻近组辅助的糖基化方法。评估了目标化合物对癌细胞的选择性细胞毒性，其中R-MTL-A对人皮肤鳞状细胞癌HSC-5细胞表现出最高的选择性细胞毒性。我们的研究结果表明，R-MTL-A 通过降低细胞膜流动性来诱导 HSC-5 细胞发生坏死样细胞死亡。 R-MTL-A 还对受损皮肤细胞表现出有效的恢复作用，表明 R-MTL-A 有潜力作为新型药妆品的先导化合物，具有癌细胞选择性毒性和对受损皮肤细胞的恢复作用。© 2024 Wiley ‐VCH 有限公司。

Mannosylerythritol lipids (MELs) are a class of amphipathic molecules bearing a hydrophilic 4-O-β-D-mannopyranosyl-D-erythritol skeleton. Here, we designed and synthesized four kinds of MEL analogues R-MEL-A ([2R,3S]-erythritol type), S-mannosylthreitol lipid (MTL)-A ([2S,3S]-threitol type), R-MTL-A ([2R,3R]-threitol type), and α-S-MEL-A ([2S,3R]-erythritol type) using our previously reported boron-mediated aglycon delivery (BMAD) method and a neighboring group assisted glycosylation method. The selective cytotoxicity of the target compounds against cancer cells was evaluated, with R-MTL-A showing the highest selective cytotoxicity against human skin squamous carcinoma HSC-5 cells. Our findings suggest that R-MTL-A induces necrosis-like cell death against HSC-5 cells by decreasing cell membrane fluidity. R-MTL-A also exhibits an efficient recovery effect on damaged skin cells, indicating that R-MTL-A has potential as a lead compound for new cosmeceuticals with both cancer cell-selective toxicity and recovery effects on damaged skin cells.© 2024 Wiley‐VCH GmbH.