Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, United States.
J Org Chem. 2010 Dec 17;75(24):8564-70. doi: 10.1021/jo1019688. Epub 2010 Nov 15.
The asymmetric synthesis of all four of the known natural phlegmarines and one synthetic derivative has been accomplished in 19-22 steps from 4-methoxy-3-(triisopropylsilyl)pyridine. Chiral N-acylpyridinium salt chemistry was used twice to set the stereocenters at the C-9 and C-2' positions of the phlegmarine skeleton. Key reactions include the use of a mixed Grignard reagent for the second N-acylpyridinium salt addition, zinc/acetic acid reduction of a complex dihydropyridone, and a von Braun cyanogen bromide N-demethylation of a late intermediate. These syntheses confirmed the absolute stereochemistry of all of the known phlegmarines.
已从 4-甲氧基-3-(三异丙基甲硅烷基)吡啶通过 19-22 步不对称合成了所有四种已知天然的菲玛啉和一种合成衍生物。手性 N-酰基吡啶鎓盐化学被两次用于在菲玛啉骨架的 C-9 和 C-2' 位置设置立体中心。关键反应包括使用混合格氏试剂进行第二次 N-酰基吡啶鎓盐加成、锌/乙酸还原复杂的二氢吡啶酮以及晚期中间体的冯·布朗氰化溴 N-去甲基化。这些合成证实了所有已知菲玛啉的绝对立体化学。
