U.S.-Korea Cooperative Research: Reduction of NAD+ Analoguesby Phosphonate

该提案要求资助美国明尼苏达大学化学系Maurice M. Kreevoy博士与江原大学科学教育研究所化学系Lee In-Sook博士进行为期24个月以上的研究。用膦酸单钠或二钠还原NAD类似物（烟酰胺季铵盐）的合作研究项目，包括吡啶、喹啉、吖啶和卤代菲钍。这种还原的性质将通过仪器技术表征产物，并通过动力学方法确定反应的机制来探索。烟酰胺季铵盐及其类似物的还原一直是一个长期存在的目标，因为这一过程在生物系统中具有重要意义，并且可能在合成转化中使用烟酰胺酶。虽然这些反应中的许多在实际的有机合成中可能是有价值的，但这种类型的酶催化氧化还原反应并不是很成功，因为还原的辅因子生产成本昂贵，有些没有商业上的可用性，有些在溶液中不稳定，还有一些留下不希望的副产物。膦酸盐用作还原剂有几个优点，即它是一种足够强的还原剂，可以与各种NAD类似物发生广泛的反应，而且价格低廉，可买到，在溶液中稳定，其最终产物不太可能产生副反应。该项目与美韩合作科学项目的目标相关，该项目旨在通过科学信息、思想、技能和技术的交流以及在互利问题上的合作，提高美韩科学家和工程师之间的合作水平。这个项目将为克里沃伊博士的研究增加一个国际合作的维度。切——8520903。

This proposal requests funds to permit Dr. Maurice M. Kreevoy, Department of Chemistry, University of Minnesota, to pursue with Dr. In-Sook Han Lee, Department of Chemistry, Science Education Research Institute, Kangweon National University, for a period of 24 + months, a program of cooperative research on the reduction of NAD analogues (nicotinamide quarternary salts), including pyridinium, quinolinium, acridinium, and phenanthridinium halides, by mono- or disodium phosphonate. The nature of this reduction will be explored by characterizing the products by instrumental techniques and by determining the mechanism of the reaction by kinetic methods. The reduction of nicotinamide quarternary salts and their analogs has been a long standing objective because of the great importance of this process in biological systems and the possible use of nicotinamide enzymes in synthetic transformation. Although many of these reactions could be valuable in practical organic synthesis, enzyme-catalyzed oxidation-reduction reactions of this type have not been very successful because the reduced cofactors are expensive to produce, some are not commercially available, some are unstable in solution, and others leave undesirable by-products. Phosphonate used as a reducing agent has several advantages, namely, it is a strong enough reducing + agent to produce a wide range of reactions with a variety of NAD analogs and it is inexpensive, commercially available, stable in solution, and its end product is not likely to produce side reactions. This project is relevant to the objectives of the U.S.-Korea Cooperative Science Program which seeks to increase the level of cooperation between U.S. and Korean scientists and engineers through the exchange of scientific information, ideas, skills, and techniques and through collaboration on problems of mutual benefit. This project will add an international cooperative dimension to Dr. Kreevoy's research under NSF Grant No. CHE-8520903.