A glove box to enable transition metal-catalyzed reactions in the Yudin lab

两性分子-具有正交反应性节点的双功能结构-一直是我们研究的重点。在过去的24个月里，我们发表了3篇重要的论文，描述了：(a)在大环结构中安装杂环接枝的新方法（Nature Chem. 2016,8,11050）， (b)硼化物转移反应的机制基础（Nature Chem. 2017，出版中），以及(c)展示了硼在富含杂原子的蛋白质环境中的独特配位偏好（Nature Chem. 2017, 9,731）。由于缺乏专用的手套箱，我们无法在大环化学和硼化学方面取得进展。事实上，我们进行了一次内部投票，手套箱成为了新装备的首选。考虑到我的学生工作有多努力，我敢肯定手套箱一周7天都在使用。手套箱中的化学物质反映了该设备所在实验室的研究兴趣，而与其他人的材料交叉污染是不应共享仪器的首要原因。我的学生没有任何地方可以进行需要惰性气氛的实验，但很明显，我们的下一波进展很可能来自过渡金属催化的大环转化以及富含杂原子的有机硼化合物。如果推迟收购手套箱，就很难在这个竞争极其激烈的领域迅速取得进展。然而，如果我们获得手套箱，我们将能够在我们最近的突破的基础上，设计过渡金属催化的大环转化，以调节它们的极性表面积。目前，我们对宏观循环的研究还没有涉及到需要惰性气氛的金属催化。然而，我们已经发表了一些有影响力的文章，表明对大环的合成操纵可以极大地影响它们的性质。添加一个未开发的功能将类似于将我们的程序放入一个新的齿轮，这是理所当然的。除了明显丧失发表高水平论文的能力外，我们的专利地位也将受到影响。最令人担忧的是，没有办法在复杂分子合成和金属催化的界面上进行令人兴奋的项目，将影响我招募顶尖人才到我的实验室的能力，并将从培训HQP中移除一个有吸引力的部分。制药公司（默克、BMS、吉利德）经常从我的实验室招聘人员，这表明我们提供的培训被认为是有价值的。我们已经用尽了非金属媒介制作大周期的方法，我的学生需要扩大他们的视野。我们的实验室认为，金属催化是最有可能的方式，将确保我们的研究战略重要领域的快速进展。

Amphoteric molecules – bifunctional structures equipped with orthogonal nodes of reactivity – have been the focus of our research program. Over the past 24 months we have published 3 pivotal papers that describe: (a) a new way of installing heterocyclic grafts in the structures of macrocycles (Nature Chem. 2016, 8, 11050), (b) mechanistic underpinnings of boride transfer reactions (Nature Chem. 2017, in press), and (c) showcaser boron’s unique coordination preferences in heteroatom-rich protein environments (Nature Chem. 2017, 9, 731). We are prevented from making advances in macrocycle chemistry and boron chemistry by the absence of a dedicated glovebox. In fact, we performed an internal vote and glovebox came up as the top choice for new equipment. Given how hard my students work, I am certain that the glovebox will be in use 7 days a week. Chemicals in a glovebox reflect the research interests of the lab housing the unit and cross-contamination with someone else’s material is the number one reason the instrument should not be shared. My students do not have any place where they can perform experiments that require inert atmosphere, yet it is also clear that the next wave of our advances will likely arise from transition metal catalyzed transformations of macrocycles as well as heteroatom-rich organoboron compounds. A delay in acquisition of the glovebox will make it difficult to make rapid advances in an extremely competitive field. However, if we obtain the glovebox, we will be able to build on our recent breakthroughs and design transition metal-catalyzed transformations of macrocycles in order to modulate their polar surface areas. At the moment, none of our research on macrocycles involves metal catalysis that requires inert atmosphere. However, we have published influential accounts suggesting that synthetic manipulation of macrocycles can drastically affect their properties. It stands to reason that adding an unexplored capability will be akin to putting our program into a new gear. Besides the obvious loss of ability to publish high-leven papers, our patent position will suffer. Most alarmingly, not having a means to carry out exciting projects at the interface of complex molecules synthesis and metal catalysis will affect my ability to recruit top talent into my lab and will remove an attractive component out of training the HQP. Pharmaceutical companies (Merck, BMS, Gilead) routinely hire individuals out of my lab, which suggests that the training we offer is deemed valuable. We have exhausted non-metal mediated ways of making macrocycles and my students need to expand their horizons. Our lab feels that metal catalysis is the likeliest modality that will assure rapid advances in strategically important areas of our research.