A medicinal chemistry laboratory on the fourth floor of the HKUST Medical Center Building.
At this moment, Xu Yun was standing on the operating table wearing a pure cotton lab coat, with six men and women of different heights standing in front of him.
"Now that all the juniors and juniors are here, I will simply talk about half a chapter... ahem, a few words."
Xu Yun raised a stack of bound documents in his hand and quickly scanned the people in front of him:
"Yesterday morning I got the project approval receipt. Now that the procedures, venue and personnel have been finalized, our research team has been established.
Our research group does not have a mentor to lead the team. I am the applicant and the first responsible person. The laboratory is valid for two weeks. The research participation record will be registered in your files. Regardless of whether there are results or not, it can be regarded as a review.
The experience gained in the past should be somewhat helpful to everyone in the future.”
Upon hearing this, two of the six people in front of them suddenly had a hint of uncontrollable joy on their faces.
As a member of C9, the University of Science and Technology of China has an annual R&D expenditure of over 10 billion, ranking it among the ninth and tenth in the country.
Although this number seems large, after deducting a series of projects such as the 973 Plan, the 863 Plan, the National Science and Technology Support Plan, and the International Science and Technology Cooperation and Exchange Special Project, the funds and quotas allocated to each hospital are far less than it seems.
big.
Then, after losing some points to some big names, there is still money left, but there are not many high-quality project quotas left.
Many graduate students have been busy for one or two semesters and may not be able to get involved in large-scale projects. They can only be silently bossed around by their supervisors.
Therefore, when Xu Yun came to the door with the application form for Tian Liangwei's assistant project, several bitter graduate students immediately nodded their heads. The vibration frequency was like a massage stick, which almost made Xu Yun say that Chinese people don't lie.
Chinese people.
To put it bluntly, if you have participated in a project team of this level, no matter whether there are any results in the end, when you declare your salary after graduation, you will get at least 500 yuan more per 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 pheromones and third-generation imidacloprid to verify and explore the direction of fourth-generation imidacloprid. The ultimate goal is..."
As soon as he finished speaking, several junior students shouted in unison:
"Destroy Xiaoqiang!"
After saying that, everyone laughed happily.
Amid the laughter, a girl with short hair raised her hand and asked Xu Yun curiously:
"Senior, why do you have so much resentment against cockroaches?"
Xu Yun glanced at her lightly. This girl's name is Tang Yiqiu. She is a senior school girl with good grades and good reputation for her character:
"...For me, that's a sad story, but what I say will make you very happy, so I refuse to answer."
After speaking, he raised the document in his hand, and the pages rustled in the air:
"Okay, enough gossip, we have limited time. Let's test the gas masks and organic vapor filter boxes, and put on protective skirts. The test will start in fifteen minutes!"
Then he glanced at Qiu Sheng:
"Old Qiu, you check the machines and switches, and I'll go and distribute the materials."
Qiu Sheng nodded:
"clear."
Fifteen minutes later, everything was ready.
The main experimental reagents used by Xu Yun and others this time are 2-phenylpyridine, 4-hydroxymethylphenylboronic acid, 2-naphthaleneboric acid, 3-furanboronic acid, 3-benzothiopheneboronic acid, and N-phenylpyrazole.
Benzoquinoline, [Ru(p-cymene)2Cl2]2, etc.
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 stood in their respective positions.
"If you want to combine pheromones with imidacloprid, you must first cyclize CH3. I plan to complete it through a hydrogenation reduction reaction coupling the epoxy terminal alkyne and 1-bromo-2-pentyne."
On the operating table, Xu Yun expressed his thoughts and said to a tool man... Wrong, the junior said:
"Li Yan, this task is entrusted to you."
"clear!"
The Li Yan mentioned by Xu Yun is a graduate student, 24 years old this year. He took a short position and immediately started the operation after hearing the words.
At the same time, Xu Yun looked at Tang Yiqiu again:
"Xiao Tang, you are responsible for following up and trying to capture the optically active fragments of epoxy sulfonate!"
"clear!"
As we all know.
Under the catalysis of L-(+)-diisopropyl tartrate and tetraisopropyl titanium oxide, allyl alcohol will undergo a Sharpless asymmetric epoxidation reaction to obtain (2S,3R)-2,3-epoxy-
1-Tetradecanol.
Epoxy alcohol (2S,3R)-9 undergoes p-toluenesulfonylation and ring-opening with perchloric acid, and the absolute configuration of carbon atom No. 3 is flipped from R to S, yielding (2S,3S)-p-toluenesulfonic acid 2,3
-Dihydroxy-1-tetradecanol ester; then undergo ring closure with potassium carbonate and p-toluenesulfonylation to obtain (2S,3S)-p-toluenesulfonic acid 1,2-epoxy-3-tetradecanoate
Alcohol ester, 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 been captured!"
"Very good, how much is ee worth?"
"Still under measurement... Epoxy alcohol and dinitrobenzoyl chloride are still reacting... Oh, it came out, 93%!"
When Xu Yun heard this, he couldn't help but breathed a sigh of relief.
The so-called ee value refers to the enantiomeric excess. The theoretical ee value of chiral epoxy sulfonate is 90%. The 93% measured by Xiao Tang is above the horizontal line. It is considered a successful first step.
After completing the synthesis of the key optically active intermediates, the next step is to study the asymmetric synthesis of the target pheromone.
The operation of this step is to first react the epoxy sulfonate with trimethylsilyl acetylene to cause epoxy ring opening, and then treat it with potassium carbonate to close the ring and remove TMS to obtain (4S,5R)-4,5-
Epoxy-1-hexadecene, and the yield of this step is...
60%.
That’s right, the first step is 89% and the second step is 60%.
The yield rate is almost cut in half.
This is a very common situation in biochemistry. The yield decreases as you proceed, from 90% to 60%, and then 30%.
After seven or eight rings, the yield of non-normal compounds may even be only single digits.
So why is it said that scientific research costs money? In the ten minutes that Xu Yun and others started, including machine damage, they have already spent at least 1,000 yuan, which is a whole alliance leader.
The preparation of 5-epoxy-1-hexadecyne went smoothly, just when Xu Yun and others were ready to take another step forward...
I saw another graduate student responsible for doing nucleophilic substitution suddenly let out an "ah" and sighed:
"Senior, the nucleophilic substitution reaction failed..."
