.4 - Methoxycarbonyl Fentanyl Synthesis And Phosphorus Acylation Of Exploration And Research

The force of terrorism has been outspread rapidly and rampant increasingly since 1990s, especially 9.11 events occurred. It indicated that the terrorism and the anti-terrorism were entering a recent stage of development. In 2002, the hostages were held by armed militants in the theater of Moscow axletree factory, this finally led to more than 100 hostages to be death. Russian government used the fentanyl derivatives to rescue hostages. It was reported that fentanyl is a kind of powerful effect analgesic medicine in the beginning of 1960s. Because of its high analgesia intensity and particular structure, many investigators have interest in it. This kind of medicine belongs to something that cures, and its derivatives have the relevant alexipharmic noloxone, this alexipharmic can protect the hostages from being injured.Some 4-substituent fentanyl derivatives, for instance, 4-methoxycarbonyl fentanyl is one of strongest types of analgesia activities. Therefore, it is important to research fentanyl for both clinic study and anti-terrorism, especially 4-methoxycarbonyl fentanyl.Phosphore is one of important elements of bodys, and it participates in crucial metabolis -m activity of lives. Phosphorylation transfer reaction and life process are closely bound up. 4-N-acyl is very important to produce strong narcotic analgesic activities in the molecular structure of 4-methoxycarbonyl fentanyl. So far, 4-N-posphoracyl has not been reported, only 4-N-propionyl is well-informed. So we explored the synthesis path of phosphorylation reactio -n about 4-methoxycarbonyl fentanyl.In this paper, the intermediates of 4-methoxycarbonyl fentanyl about 4-N-phenyl and 4-N-cyclohexyl were prepared from 1-phenylethyl-4-piperidinone through the Strecker reacti -on, hydrolysis, esterification reaction. The Atheron-Todd reaction has been used for studying the synthesis path of phosphorylation reaction about N- phenyl-4-methoxycarbonyl fentanyl. The models such as diethyl phenylphosphoramidate and diethyl methyl(phenyl) phosphora–midate were prepared successfully. Because of steric hindrance, we had difficulty in synthesi -zing the phosphorylation reaction target product of 4-methoxycarbonyl fentanyl. And then, we hoped that we could obtain the target product through synthesizing key intermediate. In the process of preparing the intermediate, we found that the intermediate has been synthesized possibly by LC-Ms analysis. Because of low yield, the experimental conditions is in the exploratory stage.We also used the microwave catalytic synthesis method to improve on the technology of some reaction steps so that the yield increased, and the reaction time was shortened.In addition, HOMO, LUMO, charges density pictures of 4-methoxycarbonyl fentanyl derivatives molecules were obtained through calculations. At the same time, the activity part of molecules were estimated.