BACKGROUND The 5,8-disubstituted indolizidines are the largest class of poison-frog alkaloids found in anuran skin, and are of considerable interest because of their inhibitory effects on the neuronal nicotinic acetylcholine receptors. Many synthetic strategies for the construction of this nucleus have been reported: however, a flexible route has not been reported to date. RESULTS Synthesis of lactam chiral building blocks for the flexible synthesis of the title alkaloids has been achieved using a Michael-type conjugate addition reaction to a chiral cyclic enamine ester as the key step in constructing the trisubstituted piperidine ring system. To demonstrate the usefulness of these chiral building blocks, syntheses of (-)-203A, (-)-205A from 1, and (-)-219F from 2 have been achieved. CONCLUSION The total synthesis of (-)-203A, (-)-205A, and (-)-219F was achieved, and the absolute stereochemistry of natural 203A was determined to be 5S, 8R, 9S. In addition, the relative stereochemistry of natural 219F was determined.

中文翻译：

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5,8-二取代吲哚里西啶类毒蛙生物碱的灵活合成路线：常见内酰胺手性构件的合成及其在(-)-203A、(-)-205A和(-)-合成中的应用219F。

背景 5,8-二取代吲哚里西啶是在无尾蚴皮肤中发现的最大种类的毒蛙生物碱，并且由于它们对神经元烟碱型乙酰胆碱受体的抑制作用而备受关注。已经报道了许多用于构建该核的合成策略：然而，迄今为止还没有报道过灵活的路线。结果 使用迈克尔型共轭加成反应与手性环烯胺酯作为构建三取代哌啶环系统的关键步骤，已实现了用于灵活合成标题生物碱的内酰胺手性构件的合成。为了证明这些手性构件的有用性，已经实现了 (-)-203A、(-)-205A 来自 1 和 (-)-219F 来自 2 的合成。结论 (-)-203A、(-)-205A、并得到(-)-219F，确定天然203A的绝对立体化学为5S、8R、9S。此外，测定了天然 219F 的相对立体化学。