Lan Ping, Jackson Colin J, Banwell Martin G, Willis Anthony C
Research School of Chemistry, Institute of Advanced Studies, The Australian National University , Canberra, ACT 0200, Australia.
J Org Chem. 2014 Jul 18;79(14):6759-64. doi: 10.1021/jo501255c. Epub 2014 Jul 9.
The 1,9-ethanoiminomethano-bridged tetrahydrodibenzo[b,d]-furan 2, a non-natural isomer of the alkaloid (-)-galanthamine (1) varying in the manner in which the D-ring is annulated to the ABC-core, has been prepared in racemic form. The synthetic sequence starts with the cyclopropane 3 and involves intramolecular Heck alkenylation and radical-based Smiles rearrangement reactions as key steps. Unlike natural product 1, but as predicted by docking studies, compound 2 is not a potent inhibitor of acetylcholine esterase.
1,9-亚乙基亚氨基甲桥连四氢二苯并[b,d]呋喃2，是生物碱（-）-加兰他敏（1）的非天然异构体，其D环与ABC核的环合方式不同，已以外消旋形式制备出来。合成路线从环丙烷3开始，关键步骤包括分子内Heck烯基化反应和基于自由基的Smiles重排反应。与天然产物1不同，但正如对接研究预测的那样，化合物2不是乙酰胆碱酯酶的有效抑制剂。
