Pandey Ganesh, Bharadwaj Kishor Chandra, Khan M Islam, Shashidhara K S, Puranik Vedavati G
Organic Chemistry Division, National Chemical Laboratory, Pune-411008, India.
Org Biomol Chem. 2008 Jul 21;6(14):2587-95. doi: 10.1039/b804278k. Epub 2008 May 20.
Various polyhydroxy piperidine azasugars have been synthesized from precursors 18a and 18b, obtained in both enantiomeric forms from d-ribose. Out of these polyhydroxy piperidine azasugars, 22, 39 and 20 were found to be potent as well as selective inhibitors of alpha-glucosidase with K(i) values ranging as low as 1.07 microM, 16.4 microM, and 88.2 microM, respectively. Replacement of the hydroxy methylene moiety of (K(i) 33% at 1 mM) by an amino methylene moiety (32, K(i) 36.8 microM) showed a remarkable increase in the activity (almost 30 times). Furthermore, increasing the lipophilicity of by N-alkylation with a dodecyl group (36) showed a three-fold enhancement in the activity (K(i) 217 microM to K(i) 72.3 microM).
多种多羟基哌啶氮杂糖已由前体18a和18b合成，这两种前体可从d-核糖以对映体形式获得。在这些多羟基哌啶氮杂糖中，发现22、39和20是α-葡萄糖苷酶的有效且选择性抑制剂，其抑制常数（K(i)）值分别低至1.07微摩尔、16.4微摩尔和88.2微摩尔。用氨基亚甲基部分（32，K(i)为36.8微摩尔）取代（1毫摩尔时K(i)为33%）的羟基亚甲基部分，活性显著增加（几乎增加了30倍）。此外，通过用十二烷基进行N-烷基化增加（化合物）的亲脂性（36），活性提高了三倍（K(i)从217微摩尔变为72.3微摩尔）。
