Five days later.
Fourth floor, a Drug Chemistry Laboratory in the Medical Center Building at USTC.
At that moment, Xu Yun stood at the workbench in a cotton lab coat. Six men and women of varying heights stood before him.
"Since you're all here, juniors, I'll just say half a chapter to start with. Ahem—just a few words."
Xu Yun raised the stack of bound documents in his hand and quickly scanned the group before him.
"Yesterday morning, I received the project approval notice. The paperwork, venue, and personnel are all in place, so our research group is officially formed.
"We don't have an advisor leading this group. I'm the applicant and the person primarily responsible. We have use of the lab for two weeks, and your participation will be recorded in your files. Whether or not we get results, this will still look good on your resumes and should help you all in the future."
At his words, two of the six immediately broke into barely restrained smiles.
As one of the C9 universities, USTC received a little over ten billion yuan in research funding each year, placing it around ninth or tenth in the country.
Though the figure looked enormous, after funding was allocated to a range of programs—the 973 Program, the 863 Program, the National Key Technology R&D Program, the Special Fund for International Science and Technology Cooperation, and others—the amount and number of grants available to each school were far smaller than they seemed.
Then the big names took their share. There might still be money left, but there weren't many high-quality project slots to go around.
Many graduate students worked hard for a semester or two without even getting a foot in the door of a major project, and could only let their advisors work them like pack animals.
So when Xu Yun came knocking with the approval documents for Tian Liangwei's subproject, the downtrodden grad students nodded at once, their heads bobbing like massage guns. They were only a few words away from making Xu Yun swear that Huaxia people never cheated other Huaxia people.
To put it bluntly, taking part in a project of this caliber could earn them at least five hundred yuan more per month when negotiating their salary after graduation, whether or not the project produced results!
Xu Yun paused, then continued:
"Our project has a simple goal: to try to combine pheromones with third-generation Imidacloprid into a new substance, and use it to verify and explore a possible direction for fourth-generation Imidacloprid. The ultimate goal is—"
As soon as he spoke, the juniors shouted in unison:
"Exterminate the roaches!"
Then they all burst out laughing.
Amid the laughter, a short-haired girl raised her hand and asked Xu Yun with a curious expression, "Senior, why do you have such a grudge against cockroaches?"
Xu Yun glanced at her. The girl was Tang Yiqiu, a senior undergraduate. She had a good academic record and a good reputation.
"To me, it's a sad story. But telling it would make you all very happy, so I refuse to answer."
He raised the documents in his hand, their pages rustling in the air.
"Okay, enough talk. We're short on time. Check your respirators and organic vapor cartridges, and make sure you're wearing your protective aprons. We'll start the experiment in fifteen minutes!"
Then he gave Qiu Sheng a meaningful look.
"Old Qiu, check the machines and circuit breakers. I'll hand out the materials."
Qiu Sheng nodded.
"Got it."
Fifteen minutes later, everything was ready.
The main reagents Xu Yun and the others were using this time included 2-phenylpyridine, 4-hydroxymethylphenylboronic acid, 2-naphthylboronic acid, 3-furanboronic acid, 3-benzothiopheneboronic acid, N-phenylpyrazole, benzoquinoline, [Ru(p-cymene)2Cl2]2, and others.
They also had more than thirty other reagents, including 2-bromopyridine, 2-bromo-4-chloropyridine, THF, DMF (N,N-dimethylformamide), DMSO, and 1,4-dioxane. (I've listed the specifics in the author's notes.)
Meanwhile, the others took their places one by one.
"To combine the pheromone with Imidacloprid, we first need to cyclize the CH3. I plan to do this through the hydrogenation-reduction reaction of an epoxy terminal alkyne and 1-bromo-2-pentyne."
At the workbench, Xu Yun explained his approach, then turned to a junior who was—no, a lab hand—and said, "Li Yi, this task is yours."
"Understood!"
Li Yi, the person Xu Yun had addressed, was a graduate student. She was twenty-four and wore her hair in a buzz cut. At his words, she immediately got to work.
At the same time, Xu Yun looked toward Tang Yiqiu.
"Xiao Tang, you're in charge of following up and trying to capture the optically active fragment of the epoxy sulfonate!"
"Understood!"
As everyone knew,
under the catalysis of L-(+)-diisopropyl tartrate and titanium tetraisopropoxide, allyl alcohol underwent Sharpless asymmetric epoxidation to produce (2S,3R)-2,3-epoxy-1-tetradecanol.
Epoxy alcohol (2S,3R)-9 underwent p-toluenesulfonylation and ring opening with perchloric acid, inverting the absolute configuration of the carbon at position 3 from R to S and yielding (2S,3S)-2,3-dihydroxy-1-tetradecyl p-toluenesulfonate. Ring closure with potassium carbonate followed by p-toluenesulfonylation then produced (2S,3S)-1,2-epoxy-3-tetradecyl p-toluenesulfonate, with a yield of 89%.
It was very simple, and easy to understand.
A few minutes later, Tang Yiqiu raised her hand again, but this time she wasn't asking why Xu Yun wanted to exterminate cockroaches.
"Senior, I've captured the epoxy sulfonate!"
"Great. What's the ee value?"
"We're still measuring it. The epoxy alcohol and dinitrobenzoyl chloride are still reacting. Oh, it's out—93%!"
Hearing that, Xu Yun let out a quiet breath of relief.
The ee value referred to the enantiomeric excess. The theoretical ee value of the chiral epoxy sulfonate was 90%, so Xiao Tang's result of 93% was above the benchmark. For now, they had successfully completed the first small step.
With the key optically active intermediate synthesized, the next step was to study the asymmetric synthesis of the target pheromone.
This step involved reacting the epoxy sulfonate with trimethylsilylacetylene to open the epoxide ring, then treating it with potassium carbonate to close the ring and remove the TMS group, producing (4S,5R)-4,5-epoxy-1-hexadecyne. The yield at this step was—
60%.
That's right: 89% for the first step, 60% for the second.
The yield had nearly been cut in half.
This was very common in biochemistry: the further along a reaction went, the lower the yield—90%, then 60%, then 30%.
After seven or eight steps, the yield of an unusual compound could even fall into the single digits.
So that was why people said research burned through money. In just the ten or so minutes since Xu Yun and the others had started, they'd spent at least a thousand yuan, including equipment wear and tear. That was a whole League of Legends subscription's worth.
The preparation of 5-epoxy-1-hexadecyne went smoothly. Just as Xu Yun and the others were getting ready to move on to the next step,
another graduate student, who was responsible for the nucleophilic substitution, suddenly let out an "Ah" and sighed.
"Senior, the nucleophilic substitution reaction failed."
Complete list of reagents:
2-phenylpyridine, p-tolylboronic acid, p-vinylphenylboronic acid, 4-hydroxymethylphenylboronic acid, 4-vinylphenylboronic acid, 2-naphthylboronic acid, 3-furanboronic acid, 3-benzothiopheneboronic acid, N-phenylpyrazole, benzoquinoline, [Ru(p-cymene)2Cl2]2.
As well as paraformaldehyde, DCM (dichloromethane), DCE, CHCl3 (chloroform), MeOH (methanol), EtOH (ethanol), EtOAc (ethyl acetate), THF (tetrahydrofuran), DMF (N,N-dimethylformamide), DMSO (dimethyl sulfoxide), 1,4-dioxane, CH3CN (acetonitrile), n-hexane, and toluene, among others.
2-bromopyridine, 2-bromo-4-chloropyridine, 2-bromo-3-methylpyridine, 2-bromo-5-methylpyridine, 2-bromo-3-fluoropyridine,
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