类胰岛素和胰岛素拮抗的碳水化合物衍生物。芳基和芳烷基 D-甘露吡喃糖苷以及 1-硫代-D-甘露吡喃糖苷的合成。

Insulin-like, and insulin-antagonistic, carbohydrate derivatives. The synthesis of aryl and aralkyl D-mannopyranosides and 1-thio-D-mannopyranosides.

作者信息

Durette P L, Shen T Y

出版信息

Carbohydr Res. 1980 Mar 15;81(2):261-74. doi: 10.1016/s0008-6215(00)85657-8.

Abstract

A number of novel, aryl and aralkyl D-mannopyranosides and 1-thio-D-mannopyranosides were synthesized for evaluation of insulin-like and insulin-antagonistic properties. The substituted-phenyl alpha-D-mannopyranosides were prepared by the general procedure of Helferich and Schmitz-Hillebrecht, the substituted-phenyl 1-thio-alpha-D-mannopyranosides by a method corresponding to the Michael synthesis of aromatic glycosides, and the aralkyl 1-thio-alpha-D-mannopyranosides by aralkylation of 2,3,4,6-tetra-O-acetyl-1-thio-alpha-D-mannopyranose (15) and subsequent O-deacetylation. Compound 15 was obtained by basic cleavage of the amidino group in 2-S-(tetra-O-acetyl-alpha-D-mannopyranosyl)-2-thiopseudourea hydrobromide, the product of the reaction of tetra-O-acetyl-alpha-D-mannosyl bromide with thiourea. Benzyl 1-thio-beta-D-mannopyranoside, obtained by reaction of the sodium salt of 1-thio-beta-D-mannopyranose with alpha-bromotoluene, and benzyl 1-thio-alpha-L-mannopyranoside were also synthesized, in order to assess the stereospecificity of the biological activities measured.

摘要

合成了一系列新型的芳基和芳烷基 D-甘露吡喃糖苷以及 1-硫代-D-甘露吡喃糖苷，用于评估其胰岛素样和胰岛素拮抗特性。取代苯基 α-D-甘露吡喃糖苷通过 Helferich 和 Schmitz-Hillebrecht 的通用方法制备，取代苯基 1-硫代-α-D-甘露吡喃糖苷通过与芳香糖苷的迈克尔合成相对应的方法制备，芳烷基 1-硫代-α-D-甘露吡喃糖苷通过 2,3,4,6-四-O-乙酰基-1-硫代-α-D-甘露吡喃糖（15）的芳烷基化以及随后的 O-脱乙酰化制备。化合物 15 通过 2-S-（四-O-乙酰基-α-D-甘露吡喃糖基）-2-硫代假脲氢溴酸盐（四-O-乙酰基-α-D-甘露糖基溴与硫脲反应的产物）中脒基的碱性裂解获得。还合成了通过 1-硫代-β-D-甘露吡喃糖的钠盐与 α-溴甲苯反应得到的苄基 1-硫代-β-D-甘露吡喃糖苷以及苄基 1-硫代-α-L-甘露吡喃糖苷，以评估所测生物活性的立体特异性。