Zhang Xiaheng, Zhou Yu, Zuo Jianping, Yu Biao
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Nat Commun. 2015 Jan 20;6:5879. doi: 10.1038/ncomms6879.
Periploside A is a pregnane hexasaccharide identified from the Chinese medicinal plant Periploca sepium, which features a unique seven-membered formyl acetal bridged orthoester (FABO) motif and potent immunosuppressive activities. Here, we show the synthesis of this molecule in a total of 76 steps with the longest linear sequence of 29 steps and 9.2% overall yield. The FABO motif is constructed via a combination of Sinaÿ's and Crich's protocol for the formation of orthoester and acetal glycosides, respectively. The 2-deoxy-β-glycosidic linkages are assembled stereoselectively with judicious choice of the glycosylation methods. The epimer at the spiro-quaternary carbon in the FABO motif has also been elaborated in a stereo-controlled manner. This epimer, as well as the synthetic analogues bearing the FABO motif, retain largely the inhibitory activities of periploside A against the proliferation of T-lymphocyte, indicating the importance of the chemical connection of the FABO motif to their immunosuppressive activity.
杠柳苷A是从中国药用植物杠柳中鉴定出的一种孕甾烷六糖，其具有独特的七元甲酰基缩醛桥连原酸酯（FABO）基序和强大的免疫抑制活性。在此，我们展示了该分子的全合成，总共76步，最长线性序列为29步，总收率为9.2%。FABO基序分别通过西奈（Sinaÿ）法和克里奇（Crich）法相结合构建原酸酯和缩醛糖苷。通过明智地选择糖基化方法，立体选择性地组装了2-脱氧-β-糖苷键。FABO基序中螺环季碳上的差向异构体也以立体控制的方式进行了阐述。该差向异构体以及带有FABO基序的合成类似物在很大程度上保留了杠柳苷A对T淋巴细胞增殖的抑制活性，表明FABO基序的化学连接对其免疫抑制活性的重要性。
