CHIRAL HETEROELEMENT REAGENTS IN ASYMMETRIC SYNTHESIS

描述：在这份续签申请中，首席调查员 表示，最近FDA的法规可能会增加 介绍新的手性药物和这项研究计划是设计 为潜在药物的合成开发低成本替代品 以对映体纯形式存在的中间体和试剂。 一项主要的努力是针对结晶的使用- 辅助不对称转化(AT)作为一种提升动力学的方法 立体选择性。手性单官能团和手性有机硼配合物 使用AT制备双功能基板。配置 通过使平衡混合物结晶来控制At B 立体异构体。 需要注意的是，随后的粘结形成过程可以发生 在立体生成的硼原子的控制下，这种方法 将应用于合成含有以下成分的手性构筑块 季碳，从氨基酸和羟基酸开始。 新型手性有机硼路易斯酸将用于不对称 转化和催化也是如此。这些试剂是用来 活化非手性亚胺和硫化物形成对映体选择性键 反应。据说，长期目标包括概念上相关的 羰基化合物和醚类的活化。 首席调查员指出，这个项目的另一个主要部分 涉及不对称合成手性羰基化合物 烯醇酸盐的质子化。他报告说，一种高效的不对称 已经为酰胺烯醇酸盐找到了质子供体，铅 化合物是一种手性苯胺。他指出，将开始努力 为了制备更简单的类似物，可以根据酸度的增加进行修改 当这一点实现时，这项技术将应用于 通过烯醇酸盐使酯去消旋化。另有声明指出， 二醇二酯的顺序去消旋化将作为一种方法来探索 达到高对映体过量。各种各样的其他基板也是 有待研究，包括α-烷氧基和α-氨基的衍生物 内酰胺、内酯、酯和酮烯醇化。 最后，将使用以下方法来探讨该技术的机械方面 光谱技术。

DESCRIPTION: In this renewal application, the principal investigator states that recent FDA regulations are likely to increase the cost of introducing new chiral drugs and that this research program is designed to develop low cost alternatives for the synthesis of potential drug intermediates and reagents in enantiomerically pure form. A major effort is to be directed toward the use of crystallization- assisted asymmetric transformation (AT) as a way to upgrade kinetic stereoselectivity. Chiral organoboronate complexes of monofunctional and difunctional substrates are to be prepared using AT. The configuration at boron is to be controlled by crystallizing an equilibrating mixture of stereoisomers. It is noted that subsequent bond forming processes can then take place under the control of the stereogenic boron atom and that this approach will be applied to the synthesis of chiral building blocks containing quaternary carbon, starting from amino and hydroxy acids. New chiral organoboron Lewis acids are to be made for use in asymmetric transformation and also in catalysis. These reagents are to be used to activate achiral imines and sulfides for enantioselective bond forming reactions. Long range goals are said to include the conceptually related activation of carbonyl compounds and ethers. The principal investigator notes that another major part of this program involves the synthesis of chiral carbonyl compound by the asymmetric protonation of enolates. He reports that a highly effective asymmetric proton donor has been found for amide enolates and that the lead compound is a chiral aniline. He notes that efforts will be initiated to prepare simpler analogs that can be modified for increased acidity and that when this is achieved, the technique will be applied to the deracemization of esters via the enolates. It is also stated that the sequential deracemization of diol diesters will be explored as a way to achieve high enantiomer excess. A variety of other substrates are also to be studied, including derivatives of alpha-alkoxy and alpha-amino lactam, lactone, ester, and ketone enolates. Finally, the mechanistic aspects of the technique are to be probed using spectroscopic techniques.