Into Unscientific

  Chapter 48 The research team is starting!

  Five days later.

  USTC Medical Center Building, a medicinal chemistry laboratory on the fourth floor.

  At this moment, Xu Yun was wearing a cotton lab coat and standing on the operating table, in front of him stood six men and women of different heights.

   "Several juniors and sisters, since everyone is here, I will briefly talk about half a chapter first. Cough cough, say a few words."

  Xu Yun raised a stack of bound documents in his hand, and his eyes quickly swept over the people in front of him:

   "Yesterday morning, I received the project approval receipt for the project. Now that the procedures, venues, and personnel have all been completed, our project team has been established.

Our project team does not have a mentor to lead the team. I am the applicant and the first person in charge. The use period of the laboratory is two weeks. The records of participation in the research will be registered in your files. Having past experience should be somewhat helpful to everyone in the future. "

  Hearing this, two of the six people in front of them suddenly showed a trace of uncontrollable joy on their faces.

   As one of the members of C9, the University of Science and Technology of China has an annual research and development expenditure of about 10 billion yuan, which is about nine or ten in China.

This figure may seem large, but after deducting a series of projects such as the 973 Program, the 863 Program, the National Science and Technology Support Program, and the International Science and Technology Cooperation and Exchange Project, the funds and quotas distributed to each hospital are far from what they seem. big.

   Then some big names took a point. There is still funds left, but there are not many places left for high-quality projects.

  Many graduate students have been busy for one or two semesters, and may not be able to touch the corners of large-scale projects. They can only be silently used by their tutors as donkeys.

Therefore, when Xu Yun came to the door with the proposal proposal for Tian Liangwei's auxiliary project, several bitter graduate students immediately nodded their heads. Chinese people.

   To put it bluntly, if you have participated in such a level of project team, no matter whether you can produce results in the end, when you declare your salary after graduation, you can ask for at least 500 yuan more a month!

   Then Xu Yun paused and continued:

   "The goal of our project is very simple. It is to try to synthesize a new substance from pheromone and the third-generation imidacloprid to verify and explore the direction of the fourth-generation imidacloprid. The ultimate goal is"

   As soon as the voice fell, several students shouted together:

   "Destroy Xiaoqiang!"

   After finishing speaking, everyone laughed happily.

  Amidst the laughter, a girl with short hair raised her hand and asked Xu Yun curiously:

   "Senior, why do you have such a big grudge against cockroaches?"

  Xu Yun glanced at her lightly. This girl is called Tang Yiqiu. She is a senior student in college with good grades and reputation:

  “.To me it’s a sad story, but telling it would make you happy, so I refuse to answer.”

   After finishing speaking, he raised the document in his hand, and the pages rattled in the air:

   "Okay, here's the gossip, we have limited time, let's test the gas masks and organic vapor filter boxes, put on the protective skirts, and start the test in fifteen minutes!"

   Then he gave Qiu Sheng a look:

   "Old Qiu, please check the machine and switch, and I will distribute the materials."

  Qiu Sheng nodded:

"clear."

   Fifteen minutes later, everything was ready.

The main experimental reagents used by Xu Yun et al. are 2-phenylpyridine, 4-hydroxymethylphenylboronic acid, 2-naphthaleneboronic acid, 3-furanboronic acid, 3-benzothiopheneboronic acid, N-phenylpyrazole, Benzoquinoline, [Ru(p-cymene)2Cl2]2 and so on.

  In addition, there are more than thirty kinds of reagents including 2-bromopyridine, 2-bromo-4-chloropyridine, THF, DMF (N,N-dimethylformamide), DMSO, 1,4-dioxane, etc. (I wrote the details in the author's words)

   At the same time, the rest of the people also stood in their positions one by one.

   "To combine pheromones with imidacloprid, CH3 must first be cyclized. I plan to complete the hydrogenation reduction reaction through the coupling of epoxy terminal alkyne and 1-bromo-2-pentyne."

  On the operating table, Xu Yun was expressing his thoughts, and at the same time told a tool man that he was wrong, and the junior said:

   "Li Yan, this task is entrusted to you."

"clear!"

  The Li Yan that Xu Yun mentioned is a graduate student, 24 years old this year, with a cropped haircut, and immediately started to operate after hearing the words.

   At the same time, Xu Yun looked at Tang Yiqiu again:

   "Xiao Tang, you are in charge of following up, trying to capture the optically active fragment of epoxy sulfonate!"

"clear!"

   Well known.

Under the catalysis of L-(+)-diisopropyl tartrate and tetraisopropyl titanium oxide, allyl alcohol will undergo Sharpless asymmetric epoxidation reaction to obtain (2S,3R)-2,3-epoxy- 1-tetradecyl alcohol.

Epoxy alcohol (2S, 3R)-9 is ring-opened by p-toluenesulfonylation and perchloric acid, and the absolute configuration of carbon atom 3 is reversed from R to S to obtain (2S, 3S)-p-toluenesulfonic acid 2,3 -Dihydroxy-1-tetradecyl alcohol ester; then through potassium carbonate ring closure and p-toluenesulfonylation, you can get (2S, 3S)-p-toluenesulfonic acid 1,2-epoxy-3-tetradecyl Alcohol esters, the yield can reach 89%.

   Very simple and easy to understand.

   A few minutes later, Tang Yiqiu raised her hand again, but this time she didn't ask why Xu Yun wanted to kill cockroaches:

   "Senior, epoxy sulfonate has caught it!"

   "Very good, what is the value of ee?"

   "The epoxy alcohol and dinitrobenzoyl chloride are still reacting during the determination. Oh, it came out, 93%!"

  Xu Yun heaved a sigh of relief when he heard this.

  The so-called ee value refers to the enantiomeric excess. The theoretical ee value of the chiral epoxy sulfonate is 90%, and the 93% measured by Xiao Tang is above the level line. Right now, it is the first small step of success.

  Completed the synthesis of key optically active intermediates, the next step is to study the asymmetric synthesis of target pheromones.

The operation of this step is to react the epoxy sulfonate with trimethylsilyl acetylene first, the epoxy ring-opening occurs, and then the ring-closing and de-TMS are treated with potassium carbonate to obtain (4S,5R)-4,5- Epoxy-1-hexadecyne, and the yield of this step is .

  60%.

  That’s right, the first step is 89%, and the second step is 60%.

   Almost halved yield.

   This is a very common situation in biochemistry. The yield decreases as you go, from 90% to 60%, and then 30%.

  After the seven or eight rings, the yield of abnormal compounds may even be only single digits.

  So why do you say that scientific research burns money? In the first ten minutes, Xu Yun and the others have already spent at least 1,000 yuan including machine loss, which is a whole leader.

  The preparation of 5-epoxy-1-hexadecyne went smoothly, just when Xu Yun and others were going to take another step forward

  I saw another graduate student in charge of nucleophilic substitution suddenly let out an 'ah' and sighed:

   "Senior, the nucleophilic substitution reaction failed."

   All experimental reagents:

2-Phenylpyridine, p-methylphenylboronic acid, p-vinylphenylboronic acid, 4-hydroxymethylphenylboronic acid, 4-vinylphenylboronic acid, 2-naphthaleneboronic acid, 3-furanboronic acid, 3-benzothiopheneboronic acid, N-phenylpyrazole, benzoquinoline, [Ru(p-cymene)2Cl2]2.

and paraformaldehyde, DCM (dichloromethane), DCE, CHCl3 (chloroform), MeOH (methanol), EtOH (ethanol), AcOEt (ethyl acetate), THF (tetrahydrofuran), DMF (N,N-dimethyl Formamide), DMSO (dimethyl sulfoxide), 1,4-dioxane (1,4-dioxane), CH3CN (acetonitrile), n-hexane (n-hexane) and toluene (toluene), etc.

   2-bromopyridine, 2-bromo-4-chloropyridine, 2-bromo-3-methylpyridine, 2-bromo-5-methylpyridine, 2-bromo-3-fluoropyridine,

  (end of this chapter)