Cross-metathesis (CM) and Keck asymmetric allylation, which allows access to defined stereochemistry of a remote side chain hydroxyl group, are the key steps in a versatile synthesis of broussonetine M (3) from the d-arabinose-derived cyclic nitrone 14. By a similar strategy, ent-broussonetine M (ent-3) and six other stereoisomers have been synthesized, respectively, starting from l-arabino-nitrone (ent-14), l-lyxo-nitrone (ent-3-epi-14), and l-xylo-nitrone (2-epi-14) in five steps, in 26%–31% overall yield. The natural product broussonetine M (3) and 10’-epi-3 were potent inhibitors of β-glucosidase (IC50 = 6.3 μM and 0.8 μM, respectively) and β-galactosidase (IC50 = 2.3 μM and 0.2 μM, respectively); while their enantiomers, ent-3 and ent-10’-epi-3, were selective and potent inhibitors of rice α-glucosidase (IC50 = 1.2 μM and 1.3 μM, respectively) and rat intestinal maltase (IC50 = 0.29 μM and 18 μM, respectively). Both the configuration of the polyhydroxylated pyrrolidine ring and C-10’ hydroxyl on the alkyl side chain affect the specificity and potency of glycosidase inhibition.

中文翻译：

---

Broussonetine M及其类似物的合成及糖苷酶抑制作用

交叉复分解 (CM) 和 Keck 不对称烯丙基化，允许访问远程侧链羟基的定义立体化学，是从 d-阿拉伯糖衍生的环硝酮 14 多功能合成 broussonetine M (3) 的关键步骤。通过类似的策略，从 l-阿拉伯-硝酮 (ent-14)、l-lyxo-硝酮 (ent-3-epi-14) 开始，分别合成了 ent-broussonetine M (ent-3) 和其他六种立体异构体) 和 l-木-硝酮 (2-epi-14) 分五个步骤，总产率为 26%–31%。天然产物 broussonetine M (3) 和 10'-epi-3 是 β-葡萄糖苷酶（IC50 分别为 6.3 μM 和 0.8 μM）和 β-半乳糖苷酶（IC50 分别为 2.3 μM 和 0.2 μM）的有效抑制剂；而它们的对映异构体 ent-3 和 ent-10'-epi-3 是水稻 α-葡萄糖苷酶的选择性和有效抑制剂（IC50 = 1.2 μM 和 1.3 μM，分别）和大鼠肠道麦芽糖酶（IC50 分别为 0.29 μM 和 18 μM）。多羟基化吡咯烷环的构型和烷基侧链上的 C-10' 羟基都会影响糖苷酶抑制的特异性和效力。