Ogawa Seiichiro, Aoyama Hiroshi, Sato Toshinori
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, Yokohama, 223-8522 Japan.
Carbohydr Res. 2002 Nov 19;337(21-23):1979-92. doi: 10.1016/s0008-6215(02)00294-x.
For the purpose of providing biologically stable building blocks for the biocombinatorial synthesis using a living cell, some ether-linked alkyl 5a-carba-beta-D-glycoside primers were prepared. The key step of the synthesis was coupling of 1-bromo-n-alkanes with the 1-OH unprotected derivatives of 5a-carba-sugar analogues of D-glucose, D-galactose, and 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine), in DMF in the presence of sodium hydride. Alternatively, alkyl carba-lactoside was synthesized by incorporation of a 5a-carba-beta-D-galactose residue into the 4-position of dodecyl beta-D-glucopyranoside. A strong and specific inhibition of beta-galactosidase (K(i) 0.67 microM, bovine liver) was found for dodecyl 5a-carba-beta-D-galactopyranoside.
为了给利用活细胞进行生物组合合成提供生物稳定的构建模块，制备了一些醚键连接的烷基5a-碳-β-D-糖苷引物。合成的关键步骤是在氢化钠存在下，于N,N-二甲基甲酰胺（DMF）中，使1-溴代正烷烃与D-葡萄糖、D-半乳糖和2-乙酰氨基-2-脱氧-D-葡萄糖（N-乙酰-D-葡萄糖胺）的5a-碳糖类似物的1-OH未保护衍生物进行偶联。另外，通过将5a-碳-β-D-半乳糖残基引入十二烷基β-D-吡喃葡萄糖苷的4位来合成烷基碳乳糖苷。发现十二烷基5a-碳-β-D-吡喃半乳糖苷对β-半乳糖苷酶（牛肝，K(i) 0.67 microM）有强烈且特异性的抑制作用。
