Biomimetic Total Synthesis of (±)-8-Oxoerymelanthine

Erymelanthine 1 and 8-oxoerymelanthine 2 are unique erythrina alkaloids containing a pyridine ring. We synthesized (±)-8-oxoerymelanthine 2 in 2.0% overall yield using the following key reactions. The characteristic 6-5-6-6-membered ring system was constructed by the stereoselective intermolecular Diels−Alder reaction. Oxidative cleavage of the aromatic D-ring was conducted chemo- and regioselectively by ozonolysis in the presence of BF3-etherate. This cleavage site is identical to the site cleaved during the biosynthesis of erymelanthine 1. Nitrogen incorporation was achieved by aminolysis. Conversion of the D-ring pyridone to the corresponding pyridine was efficiently accomplished by palladium-catalyzed reduction of aryl triflate 21. This is not only the first total synthesis of (±)-8-oxoerymelanthine 2 (where the D-ring is pyridine) but also, more importantly, a biomimetic total synthesis of an erythrinan D-aza alkaloid.

厄里美林碱1（Erymelanthine 1）与8-氧代厄里美林碱2（8-oxoerymelanthine 2）是一类独特的含吡啶环（pyridine ring）的刺桐生物碱（erythrina alkaloids）。本研究采用如下关键反应，以2.0%的总产率成功合成了(±)-8-氧代厄里美林碱2。该化合物特征性的6-5-6-六元环系通过立体选择性分子间狄尔斯-阿尔德（Diels−Alder）反应构建得到。在三氟化硼乙醚络合物（BF3-etherate）存在下，通过臭氧化反应（ozonolysis）对芳香D环进行了化学与区域选择性氧化裂解，该裂解位点与厄里美林碱1生物合成过程中的裂解位点完全一致。通过氨解反应（aminolysis）实现了氮原子的引入。利用钯催化还原三氟甲磺酸芳基酯（aryl triflate）21，可高效将D环的吡啶酮转化为对应的吡啶环。本研究不仅首次实现了(±)-8-氧代厄里美林碱2（其D环为吡啶环）的全合成，更为重要的是，完成了首例刺桐烷D-氮杂生物碱（erythrinan D-aza alkaloid）的仿生全合成。