Mukaiyama Aldol Strategy Towards the Leptosin Alkaloids

描述（由申请人提供）： 瘦素是一类分子结构复杂、具有细胞毒和抗肿瘤活性的天然产物。到目前为止，还没有报道记录这些生物碱的全合成。这种合成必须解决的更复杂的挑战之一是含有连续的全碳季中心和两个仲醇的中心bispyrrolidinindoline环系统的立体控制形成。有人建议，使用一锅双Mukaiyama羟醛缩合反应将允许季中心和相邻的仲醇的安装。在这个反应可以用来安装上述立体中心之前，有必要了解反应的立体控制元素。因此，在进行任何全合成之前，初步研究将重点研究向山羟醛反应组分的结构变化如何决定反应的立体控制。一旦理解了该反应的立体控制元素，将提出一个完成Leptosins C和K的全合成的建议。

DESCRIPTION (provided by applicant): The leptosins are a class of natural products presenting remarkable molecular complexity and potent cytotoxic and antitumor activity. Thus far, no reports documenting the total synthesis of any of these alkaloids has been published. One of the more complex challenges such a synthesis must address is the stereocontrolled formation of the central bispyrrolidinoindoline ring system containing consecutive all-carbon quaternary centers and two secondary alcohols. It is proposed that using a one-pot double Mukaiyama aldol reaction will allow for the installation of both quaternary centers and adjacent secondary alcohols. Before this reaction can be used to install the above stereogenic centers, it is necessary to understand the stereocontrolling elements of the reaction. With that, before undertaking any total syntheses preliminary studies will focus on examining how varying the structures of the reactive components of the Mukaiyama aldol dictate reaction stereocontrol. Once the stereocontrolling elements of this reaction are understood, a proposal towards completing the total syntheses of leptosins C and K will be presented.