Studies on the Development of New Reaction Modes for the Synthesis of New Drugs

We are extensively carrying out the development of new reaction modes useful for the synthesis of seed and lead compounds of new drugs by utilizing the latent active species。最近，我们已经披露了一些新的反应，如以下所示。一种新的试剂， 3，3'- （苯基磷）-二（1，3-硫唑啉-2-硫酮）被用于各种β-氨基酸的内分子脱水，以给予β-乳酸酶的核心反应，可以用于单巴actam抗生素。新的β-乳酸菌抑制剂，三氮单胞菌成功地合成了晚期的[2+2]环球添加反应与一种主要衍生物。A unique heterocyclic compound、mercaptobicyclotriazolium chloride as the pendant molecule of a remarkable 1 beta-methylcarbapenem antibiotic "biapenem"、was efficiently synthesized via the reaction cascade employing a pyrazolidine derivative and ethyl formimidate hydrochloride。新血管紧张素II （Ag II）受体拮抗剂， （acylimino）三氮唑是通过利用硝酸原子在2-三氟乙酰乙酰胺-1，3，4-三氮唑的异环动力的最后区域性激活来合成的。1，5-类型内分子非绑定S... O交互是由X射线晶体学分析和Ag II受体拮抗剂及其简单模型化合物的基本MO计算进行的。我们还开发了多种新的反应，用于药物合成物，如化学狄克曼型反应模式，以实现增强作用过程，霍纳-沃德沃斯-埃蒙斯反应，使用锡（II）-三氟酸酯和N-乙基吡啶，以及新的紧张合成[6]和[7]甲基环氯芬利用了与拉丁修饰的烯基酮系统。

We are extensively carrying out the development of new reaction modes useful for the synthesis of seed and lead compounds of new drugs by utilizing the latent active species. Recently, we have disclosed several new reactions as follows. A new reagent, 3,3'- (phenylphosphoryl) -bis (1,3-thiazolidine-2-thione) was exploited for intramolecular dehydration of various beta-amino acids to give the coreresponding beta-lactams, which could be useful for the monobactam antibiotics. New beta-lactamase inhibitors, thienamonobactams were successfully synthesized by utilizing the latent [2+2] cycloaddition reaction of diketene with an imine derivative. A unique heterocyclic compound, mercaptobicyclotriazolium chloride as the pendant molecule of a remarkable 1beta-methylcarbapenem antibiotic "biapenem", was efficiently synthesized via the reaction cascade employing a pyrazolidine derivative and ethyl formimidate hydrochloride. New angiotensin II (Ag II) receptor antagonists, (acylimino) thiadiazolines were synthesized by exploiting the latent regioselective activation of the nitrogen atom in the heterocyclic moiety of 2-trifluoroacetamido-1,3,4-thiadiazoles. 1,5-Type intramolecular nonbonding S・・・O interaction was clarified by X-ray crystallographic analyzes and abinito MO calculation of the Ag II receptor antagonists and their simple model compounds. We have also developed several new reactions useful for the drug syntheses such as a chemoselective Dieckmann-type reaction mode toward the enantiodivergent process, the Horner-Wadsworth-Emmons reaction of aryl alkyl ketones using tin (II) -triflate and N-ethylpiperidine, and syntheses of new strained [6] and [7] metacyclophanes utilizing the latent conjugated allenyl ketone systems.