State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University , Nanjing 210009, P. R. China.
J Org Chem. 2018 Jan 5;83(1):185-193. doi: 10.1021/acs.joc.7b02566. Epub 2017 Dec 14.
A facile and highly diastereoselective approach toward the synthesis of potent salacinol-type α-glucosidase inhibitors, originally isolated from plants of the genus "Salacia", was developed using the S-alkylation of thiosugars with epoxides in HFIP (∼90%, dr, α/β = ∼ 26/1). The dr ratio of the product was significantly improved by the protocol as compared to that of the conventional S-alkylation of thiosugars (dr, α/β = ∼ 8/1). The protocol could be used for gram scale synthesis of the desired compounds. The 3'-O-benzylated salacinol analogs, which are the most potent in vitro inhibitors to date, were synthesized and evaluated in vivo; all analogs suppressed blood glucose levels in maltose-loaded mice, at levels comparable to those of the antidiabetic agent, voglibose.
开发了一种简便、高度非对映选择性的方法，用于合成强效的 salacinol 型α-葡萄糖苷酶抑制剂，这些抑制剂最初是从“Salacia”属植物中分离出来的。该方法使用 HFIP（约 90%，dr，α/β=约 26/1）中硫代糖与环氧化物的 S-烷基化反应。与传统的硫代糖 S-烷基化反应相比，该方法显著提高了产物的 dr 比值（dr，α/β=约 8/1）。该方案可用于所需化合物的克级合成。合成了 3'-O-苯甲酰化的 salacinol 类似物，它们是迄今为止最有效的体外抑制剂，并在体内进行了评估；所有类似物均能抑制麦芽糖负荷小鼠的血糖水平，与抗糖尿病药物 voglibose 相当。
