Development of Novel Carbon-Carbon Bond Fragmentation Reaction by Means of Samarium Diiodide and Its Application to the Synthesis of Physiologically Active Compounds

碘化钐(II)化学的发展在有机合成中一直受到人们的关注，因为它具有非常独特和有用的性质，例如除了化学选择性外，还具有粉末还原能力。尽管到目前为止，人们研究了使用二碘化钐进行各种有用的转化，但很少有人关注碎裂反应。因此，我们试图开发一种利用二碘化钐进行还原碳碳键断裂反应的有效方法，发现伽马-卤代羰基化合物与二碘化钐的反应高产率地提供了区域选择性的裂解反应产物。将该反应应用于单萜类香芹酮衍生的伽马-赫罗酯，可以制备出有用的手性构筑块，并以此为起始原料，立体选择性地合成了抗肿瘤化合物(-)-香豆素A。此外，该合成策略还被应用于顺式威士忌内酯和榄香烯内酯等伽马-内酯化合物的有效合成。还以光学纯的形式合成了具有生物意义的哌啶生物碱，(-)-无氢呋喃大黄胺、(-)-纽佛拉胺、(-)-努苯宁和(+)-3-环丁基丁胺，以及(-)-吡咯里西定生物碱。最后，以此裂解反应为关键步骤，建立了大吡咯里西丁生物碱、巴比妥酸和马兜铃酸内酯的蜜酸组分的立体选择性合成工艺。这些结果清楚地表明，新开发的二碘化钐促进了伽马卤酯的裂解反应，是合成各种生理活性化合物的有用反应。

Development of the chemistry of samarium (II) iodide has been of continuing interest in organic synthesis because of its quite unique and useful properties, such as poweful reducing ability in addition to the chemoselectivity. Although the variety of useful transformation using samarium diiodide are investigated to date, little attention has focused on the fragmentatin reaction. We have there fore attempted to develop an efficient method for the reductive carbon-carbon bond cleavage reaction by utilization of samarium diiodide and found that the reaction of gamma-halo carbonyl compounds with samarium diiodide afforded the regioselective fragmentation reaction products in high yields. When this reaction was applied to the gamma-helo ester, derived from monoterpene carvone, the useful chiral building block could be prepared.Using the chiral building block as a starting material, the synthesis of (-)-oudemansin A, an antitumour compound, was achieved stereoselectively. Moreover this synthetic strategy was applied to the efficinet synthesis of gamma-lactonic compounds, such as cis-whisky lactone and eldanolide. The biologically interesting piperidine alkaloids, (-)-anhydronupharamine, (-)-nupharamine, (-)-nuphenine and (+)-3-epinupharamine, and pyrrolizidine alkaloid, (-)-heliotidane, were also synthesized in optically pure forms. Finally stereoselective synthetic procedures for the necic acid components of macropyrrolizidine alkaloids, crobarbatic acid andintegerrinecic acid lactone were established by utilization of this fragmentation reaction as a key step.These results clearly indicated that the newly developed samarium diiodide promoted fragmentation reaction of gamma-halo esters is a useful reaction in the synthesis of various types of physiologically active compounds.