Synthetic Studies on Nitrogen Containing Natural Products

结合我们最近关于2-和4-硝基苯磺酰胺的新用途的报道，其为仲胺的合成提供了一种有效的方法，我们已经开发了2，4-二硝基苯磺酰胺胺保护基，其在2-硝基苯磺酰胺存在下经历异常容易和选择性的脱保护。这些磺酰胺化合物可用于多种二胺的合成，利用我们的仲胺合成和吲哚合成方法，我们可以实现（（）SY.+-.（））-长春新碱和（-）-他勃松碱。两种全合成的共同3-吲哚乙醇部分由异腈制备，然后在一锅中在吲哚2-位上引入丙烯酸酯部分。在Mitsunobu条件下，吲哚部分和被保护为2，4-二硝基苯磺酰胺的胺部分的缩合得到环化前体。在温和条件下，通过二氢塞克丁中间体，将吲哚NH和2，4-二硝基磺酰胺基团上的Boc保护基去除，得到所需的五环骨架。这些合成方法是合成该类化合物的最直接的方法。在报道的三组全合成钩吻素的方法中，控制spino-oxiindole部分的立体化学仍然是一个问题。通过在氧化吲哚单元上引入碘取代基，可以克服这一问题，实现钩吻碱外消旋体的立体控制全合成。在此基础上，通过不对称Diels-Alder反应和刘易斯酸介导的环氧双环[2.2.1]庚烯重排反应，合成了光学活性化合物-

In connection with our recent report on the novel use of 2- and 4-nitrobenzenesulfonamide that provides an efficient way for the synthesis of secondary amines, we have developed 2,4-dinitrobenzenesulfonamides amine protective group, which undergo exceptionally facile and selective deprotection in the presence of 2-nitrobenzenzenesulfonamides. Combination of these sulfonamides could be used for the preparation of wide variety of diamines.Using our protocol for the preparation of secondary amines and indole synthesis previously reported, we could achieve highly efficient total syntheses of ((]SY.+-。[))-vincadifformine and (-) -tabersonine. The common 3-indole ethanol part for both total syntheses was prepared from isonitrile, followed by introduction of acrylate moiety on the indole 2-position in one pot. Condensation of the indole part and the amine moiety protected as 2,4-dinitrobenzenesulfonamide under Mitsunobu condition gave cyclization precursors. Removal of Boc protective groups on indole NH and 2,4-dinitrosulfonamide group in mild condition furnished the desired pentacyclic skeletons via dihydrosecodine intermediate. These syntheses represents the most straightforward way to synthesize this class of compounds.Controlling the stereochemistry of the spino-oxiindole moiety remained as a problem in the reported total syntheses of gelsemine by three groups. We could overcome this issue by the introduction of iodine substituent on the oxiindole unit and could achieve stereocontrolled total synthesis of gelsemine in racemic form. Furthermore, the key intermediate in our racemic total synthesis was synthesized as an optically active compound by asymmetric Diels-Alder reaction and Lewis acid mediated rearrangement of epoxybicyclo [2.2.1] heptene system as key reactions.