The Birch Reduction, the Dodge Reaction, and the Shen Qi Reaction
When Shen Nuo Fei was a few months old, she learned to roll over, crawl, and say "daddy" and "mommy."
As the saying goes, children need seven or eight teeth to grow. Nowadays, children are well-nourished, and Shen Nuo Fei started teething when she was only three or four months old.
One-year-old Shen Nuo Fei has learned to walk, but this girl is naughty. Even though she can walk, she insists on being carried by her father when they go out, and she will cause trouble if he doesn't carry her.
Shen Qi finished his work for the day and took his daughter out for some fresh air.
"Nofi, you weigh over forty pounds, which is equivalent to me carrying a bag of rice for a walk every day. My dear daughter, can you get down and walk by yourself for a while?" Shen Qi said to his daughter, making a move to put her down.
"Hug me!" Shen Nuo Fei grabbed Shen Qi's clothes, refusing to get down.
Shen Nuo Fei can understand many sentences and can use simple two-word phrases such as "daddy," "mommy," and "hug" fluently.
Today's young parents are increasingly well-educated and place greater emphasis on their children's early education.
In families with adequate economic conditions, parents typically provide their children with systematic early education from a very young age.
Ordinary parents cannot be all-encompassing and knowledgeable in every aspect, which is why all kinds of early education classes are booming.
Shen Qi is quite knowledgeable, and during his time as a stay-at-home dad, he personally guided Shen Nuo Fei in learning various subjects.
Shen Qi can teach a wide range of subjects, including Science and Engineering, biology, language, English, history, politics, astronomy, geography, and physical education. All of these subjects are taught at a professional level or above, and he could easily guide a one-year-old girl.
Shen Qi is not professional enough in the arts. He wants to teach Shen Nuo Fei piano, ballet, and belly dancing, but unfortunately his own level in these arts is limited.
Shen Qi spends half of his day as a stay-at-home dad and the other half as a professor.
Ou Beiqi Pharmaceutical sent Shen Qi their latest report on animal experiments regarding C01C, which has now progressed to the dog experiments.
The experimental report showed that dogs experienced severe vomiting after taking CO1C.
A septum between a mouse's two stomachs prevents it from burping or vomiting.
Mammals such as dogs, cats, and monkeys are particularly sensitive to vomiting; they will vomit if they eat food that makes them feel unwell.
Vomiting is actually a form of protection for organisms; animals that cannot vomit are highly susceptible to poisoning.
After the dog took CO1C, it vomited to the point of despair, which caught Shen Qi's attention.
C01C contains active substances and a vomiting test is required.
Vomiting is a relatively mild type of drug side effect and is one of the side effects that is allowed to pass review.
However, Shen Qi was worried because C01C elicited such a strong vomiting reaction in dogs.
The purpose of animal testing is to observe whether animals experience severe allergies, birth defects, or even death. Drugs that fail animal testing are definitely not safe for human consumption and are not qualified for clinical trials.
Animal testing typically lasts for a year, and about 30% of new drugs fail during this stage.
Ou Beiqi Pharmaceutical's R&D department is actually located at Yanda University. Shen Qi summoned Old Yan and Cheng Haonan to re-examine the synthetic route design, structural analysis, laboratory test data, and other aspects of C01C.
"Did something go wrong with the animal testing of C01C?" Old Yan asked.
Shen Qi nodded and said, "Yes, CO1C has serious side effects on experimental dogs. One dog was euthanized because of its extremely severe vomiting and unbearable pain. So we need to improve CO1C."
A laboratory team developing a new chemical drug typically consists of about ten chemists and two or three researchers specializing in biology.
Shen Qi's drug development team consists of only three people: Old Yan and Cheng Haonan are chemists, and Shen Qi will fill the rest of the gaps.
Shen Qi could certainly recruit some new people, but the C01C project is rather special. C01C was initially synthesized by Shen Qi Team in the Yanda laboratory, and later the patent development rights were sold to Ou Beiqi Pharmaceutical at market price.
Regarding the C01C project, Shen Qi didn't want too many people involved in the research and development work, so he had to do the hard work himself.
"That's how it is with developing new products—constantly verifying and improving. I conducted some new analyses using pharmacokinetic data from laboratory dogs. CO1C contains a relatively long conjugated side chain with poor flexibility. Theoretically, reducing the double bond of this side chain can increase the compound's activity. Changes in a few letters and numbers in the molecular formula can sometimes produce huge differences in effects in in vivo experiments," Shen Qi regarding his thoughts on improving the properties of CO1C.
Cheng Haonan understood Shen Qi's meaning and asked, "So, apart from the first step, all other steps in the synthesis route of C01C need to be redesigned?"
"Yes, its parent nucleus is still benzothiazide, and we have adjusted and optimized its side chains. For easy distinction, we will internally call the optimized compound of C01C this time C01C-2." After Shen Qi finished assigning the task, in Nangang, Ou Beiqi Pharmaceutical continued to advance the animal experiments of C01C. After the dog experiments were completed, the monkey experiments would be carried out.
In the capital city, Shen Qi, Old Yan, and Cheng Haonan simultaneously carried out optimization work on C01C-2, focusing on adjusting the structure of the side chain of the benzothiazinone core in the laboratory to ultimately obtain the desired new compound. This new compound can be understood as a derivative of C01C.
In the synthesis experiment of C01C-2, Shen Qi and his team discovered a problem: after reducing the double bonds of the long conjugated side chains, the yield of the intermediate could not be reduced beyond 1%.
With a yield of only a fraction of a percent, what's the point of even trying?
"Something's not right. The yield using the Birch reduction reaction is only 0.52%?" Old Yan asked, puzzled.
In organic synthesis, the application of functional group additives in linkage and dissociation is widely used by chemists.
The first step in the C01C-2 antisynthesis is to remove the side chain, but it is not easy to break it directly. Therefore, Shen Qi and his team first established a three-membered ring, and then added one or two additives to the macrocycle to enhance the activity of the entire molecule, so that the side chain can be broken.
Up to this point, everything went smoothly, proceeding exactly as Shen Qi had planned.
However, the intermediate was ultimately obtained by Birch reduction, with a yield of only 0.52%.
The Birch reduction reaction is an organic reduction reaction in which an aromatic ring is reduced to 1,4-cyclohexadiene using sodium and alcohol in liquid ammonia.
This reaction was first published by Australian chemist Birch in 1944 and has since been widely used in chemical, pharmaceutical and other industries as well as in laboratory research and development.
The Birch Old Yan reaction, which has proven effective time and again in the synthesis of C01C, surprisingly failed in the optimization experiments for C01C-2.
Shen Qi made a decision: he no longer believed in the Birch Reduction's panacea magic. "If the Birch Reduction doesn't work, then let's try the Dodge Reaction."
"Is there Dodge Reaction?" Old Yan and Cheng Haonan racked their brains searching the brain database, but among the many organic names and reactions, they couldn't seem to find a single Dodge Reaction.
"No?"
"Is there?"
"Then let's invent a Dodge Reaction, forcibly inserting functional groups with hydrogen bond donors and acceptors, and then reducing them using the Birch Reduction." Shen Qi scribbled on the draft paper, having a new idea.
"Don't call it the Dodge Reaction. If there really is such a reaction as Boss Shen imagines, shouldn't it be named the Shen Qi Reaction according to international convention?"