Facile synthesis of neokotalanol, a potent α-glycosidase inhibitor isolated from the Ayurvedic tradi-tional medicine “Salacia”
Facile synthesis of neokotalanol, a potent α-glycosidase inhibitor isolated from the Ayurvedic tradi-tional medicine “Salacia”
复制标题
轻松合成 Neokotalanol，一种从阿育吠陀传统药物“Salacia”中分离出来的有效 α-糖苷酶抑制剂
DOI：
10.1021/acsomega.9b00610
复制
发表时间：
2019
期刊：
影响因子：
4.1
通讯作者：
Osamu Muraoka
中科院分区：
文献类型：
--
作者：
Genzoh Tanabe;Satoshi Ueda;Kazuho Kurimoto;Naoki Sonoda;Shinsuke Marumoto;Fumihiro Ishikawa;Weijia Xie;Osamu Muraoka
Neokotalanol(5)是从传统阿育吠陀药物“Salacia”中分离出来的一种磺胺型α-葡萄糖苷酶抑制剂。其抗麦芽糖淀粉酶活性比阿卡波糖强2000倍。尽管5被认为是该系列磺酸盐中活性最高的，但由于选择和设计受保护的关键中间体困难，迄今尚未建立一种简便有效的合成方案。在这项研究中，我们成功地设计了一种适当保护的环氧化物（β-20），并从容易接近的半乳糖中非对映选择性地合成了它（18）。通过使用β-20，硫化物（7b）的s -烷基化以高度非对对选择性的方式成功进行，获得了良好的总收率（11%，通过14步），优于先前报道的三个序列（15步~ 1%，18步~ 0.5%，14步~ 2%）。
Neokotalanol (5) is a sulfonium-type α-glucosidase inhibitor isolated from the traditional Ayurvedic medicine “Salacia.” Its potency against maltase-glucoamylase was 2000-fold stronger than acarbose. Despite5having been recognized as the most active among this series of sulfonium salts, a facile and effective synthetic protocol leading to5has not been established to date because of the difficulty in selecting and designing a protected key intermediate. In this study, an appropriately protected epoxide (β-20) was successfully designed and diastereoselectively synthesized from the easily accessibled-galactose (18). By use ofβ-20, S-alkylation of sulfides (7b) was successfully proceeded in a highly diastereoselective manner to afford5in a good total yield (11%, via 14 steps), which was superior to the three previously reported sequences (∼1% via 15 steps, ∼0.5% via 18 steps, ∼2% via 14 steps).