Yohannes Daniel, Procko Kristen, Lebel Lorraine A, Fox Carol B, O'Neill Brian T
Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA.
Bioorg Med Chem Lett. 2008 Apr 1;18(7):2316-9. doi: 10.1016/j.bmcl.2008.02.078. Epub 2008 Mar 6.
A novel fused tricyclic analog (11) of cytisine has been prepared (coined 'cyfusine') and determined to have high affinity at neuronal nicotinic acetylcholine receptors. A [3+2] cycloaddition protocol permitted entry into a 3,4-differentially difunctionalized dihydropyrrole (7). The penultimate cyclization was accomplished using the modified Van Tamelen conditions developed in our earlier synthesis of (+/-)-cytisine. Sequential ring-forming reactions ([3+2] cycloaddition/cyclopropanation/pyridone cyclization) gives a unique cyclopropyl analog (16) possessing a skeleton isoatomic with that of cytisine.
已制备出一种新型的金雀花碱稠合三环类似物（11）（命名为“环金雀花碱”），并确定其对神经元烟碱型乙酰胆碱受体具有高亲和力。一种[3+2]环加成方法可用于合成3,4-二官能团化的二氢吡咯（7）。使用我们早期合成（±）-金雀花碱时开发的改良范·塔梅伦条件完成了倒数第二步环化反应。连续的成环反应（[3+2]环加成/环丙烷化/吡啶酮环化）得到了一种独特的环丙基类似物（16），其骨架与金雀花碱的骨架等原子。
