Development of Photocatalytic Organic Synthesis Processes of Next Generation

L-哌啶酸是一种光学活性的环亚氨基酸，是哌啶生物碱的基本骨架，也是多种药物有机合成的重要中间体。然而，目前还没有工业合成程序。本项目旨在开发一种新的方法，从L-赖氨酸中获得光学活性的L-哌啶酸，L-赖氨酸是一种通过工业发酵工艺生产的廉价起始原料。首先，实现了光催化剂的筛选，并发现市售的二氧化钛（二氧化钛）以及新开发的实验室制备的二氧化钛（通过HyCOM、TD和THyCA程序）显示出显著高的光催化活性，以容易地和选择性地生产L-哌啶酸。铂颗粒负载的作用，用各种方法，二氧化钛也已澄清;足够的负载分散的铂颗粒是必要的最佳光催化剂。用席夫碱的光催化转移氢化反应研究了载铂二氧化钛的光催化性能。在该筛选过程中，还澄清了无定形而不是氢氧化钛（IV）或二氧化钛水合物对于光催化反应是完全无活性的，这可能是由于光激发电子和正空穴的重组的可能性更高。其次，利用负载铂的二氧化钛对L-赖氨酸的N-环化反应进行了光催化机理研究。正空穴氧化赖氨酸中的氨基生成亚胺，亚胺水解生成羰基化合物，并与剩余的氨基发生分子内缩合反应生成环状席夫碱中间体。这被光激发电子还原，得到最终产物L-哌啶酸。

L-Pipecolinic acid, a kind of optically active cyclic imino acid, is a basic skeleton of piperidine alkaloids and useful intermediate for the organic synthesis of various drugs. However, at present, there have not been industrial synthesis procedures. This project aims to develop a novel method to obtain optically active L-pipecolinic acid from L-lysine, which is a cheap starting material produced via an industrial fermentation process. First, screening of photocatalyst was achieved and found that a commercially available titanium (IV) dioxide (titania) as well as newly developed laboratory-made titanias (via HyCOM,TD,and THyCA procedures) showed markedly high photocatalytic activity to produce L-pipecolinic acid readily and selectively. The role of platinum particles loaded on, with various methods, titania has been also clarified ; sufficient loading of dispersed platinum particles is requisite for the best photocatalyst. Such properties of platinum-loaded titanias were alSo investigated with the photocatalytic transfer hydrogenation of Schiff bases. During this screening, it was also clarified that amorphous, but not titanium (IV) hydroxide nortitania hydrate, is completely inactive toward photocatalytic reactions maybe due to the higher possibility of recombination of photoexcited electron and positive hole. Second, the mechanism of the photocatalytic N-cyclization of L-lysine was investigated by usig platunm-looded titanias. It is observed that the positive holes oxidize amino group in L-lysine intoimine which is then hydrolyzed to carbonyl compounds and intramolecularly condensed with remaining amino group into cyclic schiff base intermediate. This is reduced by photoexcited electrons to give final product, L-pipecolinic acid.