New Development of One-electron Transfer Reaction - Application to the Total Synthesis of Biologically Active Natural Products -

从植物和微生物中分离出结构复杂的含氮生物碱糖模拟物，并以可逆和竞争性的方式抑制多种糖苷酶。由于这些糖苷酶抑制剂被证明具有抗病毒、抗虫、抗糖尿病和抗癌作用以及免疫调节特性的潜力，因此它们在含氮天然产物的合成方面具有相当大的兴趣。另一方面，对于亚胺的羰基，已知两种反应，即某些n -碘烷基环亚胺的分子内barbier型反应和n -酰基内酰胺等非环亚胺与羰基化合物的偶联反应。在这方面，我们最近也报道了邻苯二甲酸亚胺与羰基化合物之间的第一个松缩交叉偶联反应及其在完全立体选择性脱氧中的应用。然而，令人惊讶的是，除了一些特殊情况外，缺乏关于钐（II）化合物对简单酰胺的反应性的研究。这应归因于它们的低反应性。本文首次报道了由SmI_2介导的内酰胺类与醛类之间的氮-碳（杂）偶联反应，得到N-α-羟基烷基化内酰胺类，并将其应用于短时间合成具有生物活性的吲哚吡啶类生物碱(-)-δ-coniceine, (+)-5-epiindolizidine 167B和(+)-lentiginosine。

Structurally complex alkaloidal sugar mimics with a nitrogen in the ring have been isolated from plants and microorganisms and inhibit various glycosidases in a reversible and competitive manner. Since such glycosidase inhibitors proved to have the potential to produce antiviral, insect antifeedant, antidiabetic, and anticancer effects as well as immune modulatory properties, they have held considerable interest in the context of the synthesis of nitrogen-containing natural products.Towards the carbonyl group of imides, on the other hand, two reactions, i.e., an intramolecular Barbier-type reaction of some N-iodoalkyl cyclic imides and a coupling reaction of acyclic imides such as N-acyllactams with carbonyl compounds are known. In this connection we have also recently reported the first pinacolic cross-coupling reaction between phthalimides and carbonyl compounds and its application to the complete stereoselective deoxygenation. However, the lack of studies concerning the reactivity of samarium (II) compounds towards simple amides is surprising except in some special cases. This should be attributed to their low reactivity.Herein we described the first nitrogen-carbon (hetero) coupling reaction between lactams and aldehydes mediated by SmI_2 to provide N-α-hydroxyalkylated lactams and its application to the short synthesis of biologically active indolizidine alkaloids, (-)-δ-coniceine, (+)-5-epiindolizidine 167B and (+)-lentiginosine in addition to the formal synthesis of an isoindolobenzazepine alkaloid, chilenine.