α-葡萄糖苷酶抑制剂Radicamine B的合成

Synthesis of Radicamine B as a α-Glucosidase Inhibitor

以D-阿拉伯糖为原料,依次合成了中间体(2R,3R,4R)-2,3,5-三-O-苄氧基-4-羟基-O-叔丁基二甲基硅基-戊醛肟(3),(2R,3S,4S)-2,3,5-三-O-苄氧基-4-碘-O-叔丁基二甲基硅基-戊醛肟(4)和(2R,3R,4R)-3,4-二-O-苄氧基-2-(苄氧甲基)-3,4-二氢-2H-吡咯-1-醇(5);5与芳基Grignard试剂进行高立体选择性的加成反应制得(2R,3R,4R,5R)-3,4-二-O-苄氧基-2-[4-(苄氧基)苯基)]-5-吡咯-1-醇(6);6经催化氢化合成Radicamine B,总收率18.5%。3和4为新化合物,其结构经1HNMR,MS和元素分析表征。

Three intermediates,（2R,3R,4R）-2,3,5-tris（benzyloxy）-4-hydroxypentanal-O-tert-butyldimethylsilyl oxime（3）,（2R,3S,4S）-2,3,5-tris（benzyloxy）-4-iodopentanal-O-butyldimethylsilyl oxime（4）,and（2R,3R,4R）-3,4-bis（benzyloxy）-2-（benzyloxymethyl）-3,4-dihydro-2H-pyrrole-1-ol（5）,were prepared successively from D-arabinose.5 reacted with aryl Grignard reagent to form（2R,3R,4R,5R）-3,4-bis（benzyloxy）-2-[4-（benzyloxy）phenyl]-5-（benzyloxymethyl）pyrrolidin-1-ol（6） with high stereoselectivity.Radicamine B was synthesized from 6 by catalytic hydrogenation in total yield of 18.5%.The novel compounds 3 and 4 were characterized by 1H NMR,MS and elemental analysis.