The distinction of person and animal depends on a person can making a tool, and synthetic chemistry is a great course that lets the mankind make better tool. Synthetic chemistry devotes oneself to the strategy with innovation or it is better that wisdom makes the element becomes, more businesslike, create new member even. What is the element? The malic mobile phone in hand of the batteries in the specific that is cancer of the perfume on lady body, cure, electric car, people... nowhere is not in the element, our life is formed by the element.
Why should study an element? Be inferior to trading an issue? Your malic mobile phone can have bided his time a day, but cannot still bide his time 10 days? "Where be to bottom limit? " this synthesizes the solution that chemistry is seeking namely. So, on September 15 with " the synthesis that changes the world is chemical " be a problem the 44th period understanding future lecture invites the whole world the most creative one of synthetic chemist with the most influential force Phil Baran, let him tell everybody synthesis how to chemistry makes the life better. The full text that Phil speech is below (partial character has adjust) :
Institutional organic chemistry, you are sacred
I talk about my passion to organic chemistry today.
If you do not know what organic chemistry home makes, let me make a bit introduction. Organic chemistry shaped the square field surface that you live almost. Without organic chemistry, literally says, we are most the person will be homeless, starve to be met dead even.
Organic chemistry can use the pharmaceuticals with new invention to make the mankind lives, the remedy on all markets is invented by organic chemistry home. Can say none exaggeratively, you eat today getting full, has well only reason is the work of organic chemistry home in agricultural and chemical domain. In this value in the large industry of billions of dollar, the insecticide with arduous new development mixes organic chemistry home agricultural drug, make the farmer can raise crop yield.
Say none exaggeratively likewise, the material that organic chemistry home creates can portray your whole life almost. I see everybody is seeing his IPad and IPhone, you think those who be less than is, those screen are made by design of organic chemistry home and complex liquid crystal.
Organic chemistry may be the most important background science, to the student, chemistry is inherent and interesting, because it can let us,act sacred part. Use organic chemistry, you can create the new material that cure and helps myriad life.
Change numerous for brief, the answer comes from nature
Regard an organic chemistry as the home, a word that I like most comes from the person that I like most, this person is Elon Musk. Before a few months, one his pushed article height to generalize us the work that the lab does in going 15 years, basically also summed up at present the current situation of organic chemistry domain: It is very easy to offer excessive design and complex solution for truly difficult question. And under photograph comparing, be aimed at same question to offer extremely simple solution is extreme difficulty.
Come for years, we are in all the time to nature go on a pilgrimage for Buddhist scriptures, in nature accumulate contained too much with life origin, with the mystery related chemical reaction. In the discovery after thorough research, the chemical combination of nature reacts the process found the solution for research and development of a lot of new drug. Here shares the case that strong influence medicine develops two synthesis organic chemistry.
The first is Ingenol, it is a kind of natural material that collects from inside weed, it is Xi of a kind of terpene (ī of Ti ē X) . Ingenol has applied at treating actinic sex keratosis inside global limits at present, the dermatosis before a kind of cancer changes.
One of the most complex case in terpene Xi are yew alcohol (Taxol) , the medicaments of dollar of billion of a kind of value. This kind of compound is applied extensively at breast cancer cure. Yew alcohol is a kind of very useful natural product, and very complex. Still have green Hao element (Artemenisin) , it is in China very famous, it is the final step of malaria of cure be usinged as. The You of You of Chinese scientist massacre that discovers this one precious and crude production also is awarded nobel prize accordingly. Still have even if above the Ingenol Mebutate of respecting (tremendous halberd alcohol is methylic butene acerbity ester) , a kind of very interesting crude production, we like it particularly, because it has the latent capacity of compact synthesis method.
A few years ago, a company of Denmark found us. They encountered a problem when using agrotechnical education and synthetic Ingenol. Entire complex method needs 45 to 55 paces, the point of view that so complex process produces from industry is unworkable. Then, we begin to think, is nature how make terpene Xi? They are from identical synthesis block sets out, be called in " biosynthesis " the generation in magical process. The kind of biosynthesis happens terpene Xi in two independent courses, can saying is two phase.
These small element lines are braided twine together, resemble knitting sweater same. Entomologist meets what affectionately says change enzymatic course for annulus. It is next in magical process of billions of years, nature invented enzymatic catalysis mechanism to absorb these hydrocarbons, namely we are so called combustion process, oxidize their translate into child, namely in front two kinds of mentioned compound, we come with them today medicaments.
Then we change enzymatic process to begin from artificial annulus, this process occurs with completely symmetrical 7 paces. Each pace forms carbon - carbolic key, it is next in final 7 steps, introduced atom of all the rest oxygen. So far, synthesize a law with respect to what invented 14 paces, and quantitative class is taller, more businesslike. This makes this Denmark company extracts this kind of complex from nature, change is the crop that enlarges kilogram of class dimensions through synthesizing a way.
Here discovered a quite serious problem, perhaps say to be in in moment of organic chemistry inchoate complete synthesis times, people is fond of production element, but the purpose is for the proof only " I can " , I can synthesize the member that gives nature with simple stuff in the lab. For instance oil this kind of simple raw material becomes complex crude production. But, organic chemistry has entered 21 centuries, synthesize a compound merely already no longer interesting. Why?
It is to make an element still be not worth merely enough, even efficiency is tall, working procedure is simple. Present synthetic element must use optimal means (Near Ideal Way) will do, arrive from A that is to say B, do not take any roundabout way, or the new and luscious group that there are any kinds in the process is changed. Synthetic chemistry has been entered " feasibility times " .
Freedom radical is not the enemy, it is a friend
The 2nd example, it is a kind of orange that is called Palau'amine natural foam rubber or plastic. I and my group spent 10 years of time to just combine it together. I say mainly below among them a crucial reaction -- oxidation reaction. What you can notice is, what happen in this reaction is in specific place joins atom of oxygen of a blue to control oxidation state completely. After was being done so, we realize this kind of reaction has specific chemistry alternative. In fact, it is reaction of a kind of freedom radical actually. As a result of this discovery, we begin to ponder over other freedom base reaction may issue more extensive real estate to give birth to an influence in medicaments setting.
Interesting is, parents can tell us to want to drink tea more, because tea contains a lot ofantioxidant to be able to keep clear of freedom radical; The teacher in the school also can tell us freedom radical is the fountainhead of the evildoing such as cancer and inflammation normally. But in organic chemistry lab, freedom radical is not the enemy, however friend, they can be derived unthinkable once upon a time the compound that go out.
3 list to mix here the case that freedom radical concerns: Coffeine, quinine and Chantix. Coffeine is likely everybody has been absorbed, besides children; Quinine, in water of force of consist in soup (mineral adds quinine) , chantix is a kind of compound in medicaments of smoke of drop of brightness luck company. We discover the structure that can use freedom radical to change these compound, think before this is impossible. E.g. , you can take a few caffein directly and its alkylation or fragrant base change, you can take quinine of a few intermediate body, undertake in the position of area diversity fragrant base change or alkylation. Finally, chantix also can use similar pattern, use freedom base will analyse and edit the member that has a problem. You can make these response in special blazing environment, because system is different among freedom radical and polarity, freedom radical does not care like water such thing.
This discovery opened the entrance door of a series of important tests, we undertook a series of reagent commercializing, say for Diversinates, each district of already alive now bound is used extensively. Since 2012, these elements had sold past whole world tens of home companies, issued 70 multinomial patent, used this kind of compound to produce thousands of kinds of analogue. What I think the people of large pharmacy company is interested this reaction truly is among them outstanding alternative. For example, you can go the shop buys a few oolong, you can are opposite directly the caffein in tea undertakes deriving changing. You can use this kind of reagent, in joining its paper cup with plastic spoon, join simple industry oxidant, put its in the pass the night on beater, arrive to see this layer color atlas again in the morning the following day (TLC) board, can discover you already originally the caffein in consist in boiled water undertook deriving changing.
To pharmaceutical chemistry home, this means the chemistry that can reach remarkable level alternative. It is OK to also be meant already will arrive of later period clinical before await choose medicaments to undertake diversification, before this needs of a lot of measure order. No less than mentions before me, we discover these reagent have first-rate use level, bring about facilitate every week a lot of patent. A company just used these reagent to file the new patent of diversification, it relies on freedom radical chemistry.
Synthesized chemistry to had done not have a surprise? Not be of course
My constant regular meeting is asked about a problem, namely " whether has synthesis matured scientificly " ? It is now the domain of remnant project, without what new thing can be discovered?
Let me answer this question with the fact. The formation that acyl amine bolts is organic chemistry in the the oldest, dullest also be the most commonly used reaction. 70 come for years, this reaction can be used countless times by chemist everyday. Accordingly, if synthesis is chemical already mature, you can think here can be discovered without what. But we examined acyl amine key to form afresh, ponder over whether possible intercept to become oxidation among the key of reductive and active ester body. If not be,make through adding the close nucleus reagent of its dehydrate, add an electron to similar intermediate system directly however, those who cause the complete and diversiform compound that before this compound becomes, never has seen is augural.
Accordingly, we revealed what how bolt through losing carbon dioxide to transfer acyl amine to form, is not evaporate. What should react is practical with acyl amine key is formed quite. For example, we can go to local supermarket buying vegetable of a few biology (Biotin) . Biology element consist in in all food, also consist in in all vitamins. Carboxyl carbon undertakes when you are forming acyl amine of the standard to bolt - the formation that carbon bolts, the purity in needing to use capsule only has the thick biology element of 4% only. We built these reaction, myself had element of this a bit biology, be no problem in order to ensure it is. We built these reaction side by side and HPLC is checked when reaction ends, it is euqally good to discover it is formed with acyl amine key actually, although we are used, is dissolvent of the prevailing in whole building and reagent.
Accordingly, with very simple and firm means key of amine of new program acyl is formed, make people can think how to make a member with different kind.
For example, this is the cancer medicaments that FDA approves. The prominent place of this kind of compound depends on it containing boracic atom, this is a kind of very strange special atom, because of it and enzymatic interaction. Normally, need of pharmaceutical chemistry home makes such member through the initiative raw material with very no-go restrospect to, because they are used, is the logic that is based on double electron. If you use carboxyl idol couplet, can make identical response, and you had had initiative raw material to be supplied in great quantities. Accordingly, you need doctor of chemical like neurosurgery to be entered in that way, purify carbon replaces it with boron, this can be finished with the speed like lightning. This is one is inside 4 minutes the reaction boric acid of carboxylic acid translate into. The color that everybody can see copper turns into from blue green, become red again finally brown, can finish inside 4 minutes from the carbolic reaction to boron.
Production element must can massive amount is produced
Had mentioned before no less than, be in " feasibility times " just making a member is cared about without the person, must be OK large-scale complex means makes a member. My work in the same placing Professor Floyd Romesberg studied a kind of antibiotic that is abandoned by silent gram group, completed complete synthesis and pharmaceutical chemistry work for the first time, he established a company later, be bought by Genentech later. The synthetic course of this antibiotic is very beautiful, because it is very useful to making analogue. But when the person when Genentech needs large-scale synthesis, they need an ideal course, this course can be manipulated the effect that changes with luscious group by protective radical, although it is,begin from the amino acid that gets easily very simply.
Accordingly, we and Genentech company joint development a kind of method, peptide alignment comes to this natural and amino acid that receives the discovery in using biology directly preparation Arylomycins, undertake preparation through simple C-H oxidation alignment. It is a target with the best way, we be able to can reduce commodity cost substantially. I will reveal no less than later, the key is to use cupreous radical oxidant. Those think to synthesize the person that has matured scientificly, there is many 200 paper to teach you you on market how can accomplish this, but be successful of these methodological neither one.
Accordingly, we need to invent a kind of new copper base oxidizer, in order to realize crucial carbon - the synthesis that carbon bolts. The result that such doing is, we can react this dimensions undertakes enlarge, it had been achieved to very large scale, genentech filed patent, the cost that make was reduced 200 multiple, the Arylomycins that makes Genentech can be based on us from clinical await choose medicaments to enter clinical. Accordingly, the combustion system that everybody can use this kind of new invention now with kilogram class dimensions has these reaction.
This is a when change chemistry very good example, the chemistry in concerning with complex in medicine namely.
In the depth of the soul of home of all organic chemistry, have the longing of the complex crude production that before wanting to make me, speaks of, be in shows terpene Xi like Ingenol and Arylomycins and this. But organic chemistry home had missed the onefold and natural product with the mainest throughout history -- DNA.
Perhaps organic chemistry home should study DNA
The trailblazer of organic chemistry bound and legend character, albert St. Moser, the survey of Scripps has joined before retire, he expresses a regret over and over to this, he regrets oneself professional career is dedicated all the time at making complex natural product, be like terpene Xi and alkaloid. Perhaps all those great organic chemistry legend should divert their attention up to now on the mankind's greatest success, namely decipher DNA structure, this element is mastering life majority secret. Ladies, gentlemen, this is a deep chemical problem, still do not have any chemist to be able to be solved.
So our lab decides not to miss this opportunity, have a try however like our group such organic chemistry home how how are DNA of new look upon and relevant compound made. It is the collaboration of another industry group and academia this. The most member in our group cooperates with industrial group, it is very important that because background science is mixed,technology and industry keep abreast of hand in hand. This is the trend of a kind of constant growth, it is very important that I think this says natively to learning and have educational sense.
The name that may make everybody feel those who astonish is approval of this kind of FDA is the medicaments of SPINRAZA, it is one kind is used at infant sweeny at present help medicaments, mix to cannot moving for agonal infant, can cure really.
They call this kind the compound infuse that returns sick at heart of justice few nucleotide fluid of its head spinal cord. Half-life is 200 days, it basically eliminated those who accompany this kind of disease all sorts of disease. The breathtaking lies to regard a kind as 13 thousand kinds of isomer at present at it mixture of this kind of interesting few nucleotide acid is sold. Their client, namely patient, must pay million dollar ability every year to take compound of this kind of compound. May you want to know how this is likely? The answer is, home of core organic chemistry did not solve this problem all the time. Why is the blame that this kind of compound has so much right mirror isomer? The answer comes from at observing a structure, you can notice this is not phosphoric acid 2 ester framework, it is by phosphoric acid 2 ester are united in wedlock together. Contrary, these are connected together jointly by phosphate, sulfur acting phosphate. This is the chemical invention 30 years ago really.
So normal alignment is gone to by inject after human body. If they do not have that structure that contain sulfur, will be gobbled up by organism instantly, because this loses all and clinical medical treatment namely,use the effect. Mix into enters sulfur atomic make these compound stable, can control and can employ at clinical. Only question is, join atom of a sulfur to be able to make chemistry challenges difficulty to increase decuple, because guess how, these phosphorous atom have a semmetry to nod now. They are hand sex, they can be right hand form or left hand form. Now chemist people need finds the method that solves this problem.
Let us retreat one pace to think, how is DNA series made, our few nucleotide acid is how compose builds. This is a paragraph of extraordinary history, can restrospect to held De Xunjue in the palm to synthesize phosphoric acid first 1955 2 ester. He shows 5 price phosphor is the key that achieves this one goal. However unfortunate is, the reaction of 5 price phosphor is active, instant it is stabler with more lively compound, but the active of reaction is not quite tall still. Accordingly, 1976, carruthers invented a kind to use tervalent phosphor chemistry, come fast compose builds phosphoric acid the method of 2 ester framework, tervalent phosphor is condition of oxidation of condition of another kind of price, unfortunate is it more flabby calm, but reaction active is taller.
Tervalent phosphor makes industrial standard. The result is, whole industry accepted the reaction active that this technology and it enhances, built all machines that use place of this kind of technology to need. Till today, had oppugned it truly without the person. It is extremely no-go, and in 30 years in the past, without any significant progress. Now, we think this is the superexcellent opportunity that allows organic chemistry to solve this one problem, then we had turned round to ponder over this problem afresh.
We have advantage of a tactics in this respect, whats do not know because of us. In scientific domain, this is very good beginning normally. Normally, if you know too much, with respect to meeting block up your creativity, often compare college graduate like dot more creative. If you see this kind of phosphor is chemical, you know that is a nightmare absolutely. Each pace involves pair of Shui Min to feel and sensitive to air caustic reagent, imagine if astronaut will do chemical test,must wear. This basically is the business that the machine allows you to finish. Besides among them a measure, other all measure do not have value completely. They did not reach any goals. In fact, all gules measure are not had strategical. Exclusive and useful measure is compose built key of oxygen of a phosphor only actually, but the everybody in the industry continues to be synthesized with huge cost and inconvenience, they had not oppugned it at all.
We decide to oppugn it, solve this problem. We decide what say like Elon Musk place to seek simple solution in that way. In this job, we are very lucky the ground and 100 when beautiful Shi Guibao (Bristol-Myers Squibb) cooperates. This is very good cooperation, we cooperate with chemist not only in the process, also have pharmaceutical chemistry home and biologist, together hand in hand, find but enlarge, practical, firm with credible solution. What we do this.
The first job that we want to do is to avoid tervalent phosphor. We do not want to handle any sensitive to air or sensitive to water chemical matter. The 2nd thing that we should do is the protection that prevents any types base. These base the group is extra is added to an element, need at least two additional measure ability to use this element.
Next, we want to overcome reaction active obstacle, enhance as active as the reaction of 5 price phosphor issue namely. This is another our domain is dogmatic, people says over and over insoluble. Finally, we need to stabilize implementation to protect true hand sex to deliver highly: How to control phosphor the right hand of stereochemistry or left hand, and with one kind holds the means that charge to undertake be syntheticed automatically easily. We begin the operation later. This is a few Zhou Qian releases, it already by BMS patent application.
I tell you clear what we send simply. We say for phosphor - sulfur combines reagent, abbreviation PSI, Ψ . PSI lets you get crystallization sex intermediate body, bypass tervalent phosphor is achieved completely with 20 centuries 70 time react identically level, but the concise sex of the primitive method that has 50 time story. So Ψ is a modular compose builds system, we pass those who change module to leave base round, we can change reaction, through changing hand sex framework, we can change hand sex to deliver.
We chose a kind of very simple reagent, it originates actually food. Citric Xi. Everyone has had citric Xi, want you to had eaten breakfast, lunch or fruit only. It is in China is everywhere, you are OK a few money can buy on one gram. It is a kind of extremely simple reagent that is based on compose of 5 price phosphor to build system, can let your reliably to load nucleotide now and them occasionally couplet, form the sulfur with be had very important the few nucleotide that ester of acting phosphoric acid links is acerbity, join of ester of acting phosphoric acid has sulfur to be able to accuse completely, high yield and fidelity. Use regulation is very simple and can forecast, of the right hand or left hand form reflect to mirrorring already commercialized, if what you see, 100 when beautiful Shi Guibao is using this kind of reagent to make 2 nucleotide acid ceaselessly, even if large-scale also do not have any problems.
One day does or 10 days? Which good?
The close nucleus of all types can use alcohol not only in reagent, and still can use amine and acyl amine. You are OK assail another problem, a very serious in modern medicine problem, that is the new approach that modern medicine is immune therapeutics and immune oncology, it is called STING way, it basically can arm your immune system goes atttacking tumor. The problem depends on these elements needing to produce these effects actually, and STING is much pace synthesis, its are completely fluky and cannot mass production, because they use tervalent phosphor. The result is ideal sex low, and mixed a lot of different outcome. Those who form bright contrast is, 5 price phosphor can make you complete alter an aspect, make an identical compound that has tall ideal sex and the stereochemistry that can accuse completely.
This is an example of pharmaceutical chemistry home. This is the terrestrial war of a be worthy of the name. Besides among them all measure besides a few measure are wasteful completely. A chemist needs two half week ability to make a kind of compound. What form bright contrast to it is, phosphor - system of sulfur combination reagent allows you to be used through simple ground occasionally couplet reaction, 10 kinds of compound can be made inside a day. Everybody sees here this natural 2 alcohol, you can use natural 2 alcohol directly, change reaction to undertake very simple annulus is changed through big ring, you can control stereochemistry completely. You can choose to use which kinds of means, the flower obtains a kind of compound to make 10 next between one climate, perhaps cost two weeks of time of half to obtain the mixture of compound, and can make only.
Return example of few nucleotide acerbity complex to go up. Of course, if you can change few nucleotide acid to synthesize thoroughly, that will realize a quantity to produce greatly. In fact you are OK. Use reagent of 5 price phosphor, you can use simple reagent to have these reaction on experimental stage. See HPLC, it is the purity that has a kind of compound only, is not mixed and disorderly mixture. Even if the simplest reagent and equipment, these reaction also can be finished. In fact, you can use standard peptide to synthesize appearance to make few nucleotide acid now, amount of appearance of this kind of synthesis is large, valence actor, perhaps synthesize appearance with few nucleotide acid. We believe this will change people to make the way of few nucleotide acid in industry. It reminds people clearly, organic chemistry can change any fields of its bring into contact with.
I discussed the case of a few items that medicine and synthetic concern reflected in a few our labs simply today. We say to change chemistry. I spoke of freedom radical, and they bring about organic element combination new think. Finally, I spoke of biology element synthesizing the ideal of the times. No matter you are researching acid of nucleotide of a kind of alkaloid, peptide, few, biology preparation, small organic or it is perfume, be indifferent to. Organic chemistry, synthesis organic chemistry can be affected all these domains are more even domain.
A bit this second speech is the most important, I should thank those people that share these works, the student of the one swarm plod that comes for years and postdoctoral. Have a lot of coming from among them China, they made contribution for these projects, I appreciate them forever.
I also thank prospective forum to give me this rare chance very much.
