The Organic synthesis is the study of how we make molecules ranging from complex, biologically active natural products to new materials. As the synthesis lets a chemist to construct wholly new structures, it authorizes chemists to probe the world around them in new, creative manners. Can we make new molecules which particularly deliver drugs to targeted cancer cells? Can we manufacture molecular libraries which let us to map the three-dimensional (3-D) needs of a receptor? Can we form new, more proficient routes for constructing the complex molecular architectures found out in natural products? Can we make new catalysts for inducing asymmetry to a chemical reaction? Can we manufacture new nano-structures capable of delivering the biological agents to several cells within the body?
Organic synthesis is basically a special stream of chemical synthesis and is mainly concerned by the construction of organic compounds through organic reactions. The organic molecules often comprises of a higher level of complexity as compare to purely inorganic compounds, in such a way that the synthesis of organic compounds has developed to one of the most significant streams of organic chemistry. There are some major areas of research in the general area of organic synthesis: total synthesis, semi-synthesis and methodology.
Synthesis of Organic Molecules:
Wohler synthesis of Urea in the year 1828 heralded the birth of the modern chemistry. The Art of synthesis is as old as the Organic chemistry itself. Natural product chemistry is resolutely rooted in the science of degrading a molecule to recognized smaller molecules by employing known chemical reactions and conforming the assigned structure through chemical synthesis from small, recognized molecules by using well established synthetic chemistry methods. Once this art of manufacturing a molecule was mastered, chemists attempted to change bioactive molecules in an attempt to build up new drugs and as well to unravel the mystery of bimolecular interactions. Till the middle of 20th Century, organic chemists approached the task of synthesis of molecules as independent tailor made projects, guided mostly via chemical intuition and a sound knowledge of chemical reactions. Throughout this period, a strong foundation was laid for the growth of mechanistic principles of organic reactions, new reactions and reagents. More than a century of such intensive studies on the chemistry of carbohydrates, terpenes, alkaloids and steroids laid the base for the growth of logical approaches for the synthesis of molecules.
The duty of a synthetic chemist is identical to that of an architect (or civil engineer). As the architect could in reality see the building he is constructing, a molecular architect termed as Chemist is handicapped via the fact that the molecule he is manufacturing is too small to be seen even via the most powerful microscope developed to date. By such a restriction, how does he 'see' the developing structure? For this aim, a chemist makes utilization of spectroscopic tools. How does he cut, tailor and glue the components on a molecule which he can't see? For this aim chemists have developed molecular level tools known as Reagents and Reactions. How does he clean the debris and generate pure molecules? This feat is accomplished through crystallization, distillation and extensive utilization of Chromatography methods. A mastery over some such methods lets the molecular architect (that is, popularly termed as organic chemist) to accomplish the challenging task of synthesizing the mirade molecular structures encountered in the Natural Products Chemistry, Drug Chemistry and modern Molecular Materials. In this task, he is further guided through some 'thumb rules' that chemists have progressed over the past two centuries.
Organic Synthesis: A brief History
At the dawn of the 21st century, the state of the art and science of organic synthesis is as healthy and energetic is as ever. The birth of this multifaceted, exciting and boundless science is marked via Wohler's synthesis of urea in the year 1828. This milestone event - as trivial as it might seem by nowadays standards - contributed to a 'demystification of nature' and illuminated the entrance to a path that afterward led to big heights and countless rich dividends for humankind. Being both an accurate science and a fine art, this stream has been driven via the constant flow of beautiful molecular architectures from nature and serves up as the engine which drives the more general field of organic synthesis forward. The organic synthesis is considered, to a big extent, to be responsible for some of the most exciting and vital discoveries of the 20th century in biology, chemistry and medicine and carries on to fuel the drug discovery and development procedure by myriad processes and compound for latest biomedical breakthroughs and applications. Nowadays, natural product total synthesis is related by prudent and tasteful choice of challenging and preferably biologically significant target molecules; the discovery and invention of latest synthetic strategies and technologies; and explorations in chemical biology via molecular design and mechanistic studies. The future strides in the field are probable to be aided through advances in the isolation and characterization of novel molecular targets from nature, the availability of new reagents and synthetic processes, and information and automation technologies. These advances are destined to bring the power of organic synthesis closer to, or even beyond, the boundaries stated by nature, that, at present, and in spite of our many advantages, still look so far away.
In early days, the chemistry of natural product and its organic synthesis fascinated a very lively interest. New substances, more or less complex, more or less helpful, were constantly discovered and investigated. For the determination of the structure, the architecture of molecule, we have nowadays very powerful tools, often borrowed from the Physical Chemistry. The organic chemists of year 1900 would have been very much amazed if they had heard of the techniques now at hand. Though, one can't state the work is simpler; the steadily enhancing processes make it possible to attack more and more hard problems and the capability of Nature to form complicated substances has, as it seems, no limits.
In the investigation of a complex substance, the investigator is sooner or later confronted by the problem of synthesis, of the preparation of the substance via chemical methods. He can have different motives. Possibly he wants to check the accuracy of the structure he has found. Possibly he wants to enhance our knowledge of the reactions and the chemical properties of the molecule. Whenever the substance is of practical significance, he might hope that the synthetic compound will be less costly or more simply accessible as compare to the natural product. It can as well be desirable to change several details in the molecular structure. The antibiotic substance of medical significance is often first isolated from the microorganism, possibly a mold or a germ. There ought to susbsist a number of related compounds having similar effect; they might be more or less potent; some might possibly have undesirable secondary effects. This is by no means, or even probable, the compound produced by the microorganism - most probable as a weapon in the struggle for existence - is much excellent from the medicinal view-point. If it is possible to manufacture the compound, it will as well be possible to vary the details of the structure and to find the most efficient remedies.
Organic Synthesis in the 20th Century:
The twentieth century has been an age of massive scientific expansion and technological growth. To be sure, we now stand at the highest point of the human achievement in science and technology, and the 21st century assures to be even more revealing and rewarding. Advances in the computer science, medicine, communication and transportation have dramatically altered the manner we live and the way we interact by world around us. The huge amount of wealth has been made and opportunities for latest enterprises proliferate. This is clear that at the heart of this technological rebellion has been science and one can't deny that fundamental research has given the base for this to take place.
Chemistry has played an important and vital role in shaping the twentieth century. Oil, for illustration, has reached its potential just after chemistry allowed it analysis, fractionation and transformation to myriad of helpful products like kerosene and other fuels. The synthetic organic chemistry is possibly the most expressive stream of the science of chemistry in view of its creative power and limitless scope. To value its impact on modern humanity one just has to look around and recognize that his science is a pillar at the back pharmaceuticals, high-tech materials, polymers, pesticides, fertilizers, cosmetics and clothing. The engine which drives forward and sharpens our capability to make such molecules via chemical synthesis (that is, from which can pick and select the most suitable for each application) is total synthesis. In its question to build the most complex and challenging of nature's products, this attempt - possibly more than any other - becomes the main driving force for the progression of the art and science of organic synthesis. Therefore, its value as a research discipline broadens beyond providing a test for the state-of-the-art. This offers the opportunity to discover and discover new science in chemistry and related disciplines, and also to train, in a most rigorous manner, young practitioners whose expertise might feed various peripheral areas of science and technology
Different Aspects of Organic Synthesis:
The drive to enhance the effectiveness of the drug discovery procedure has created the requirement for rapid compound synthesis and proficient processes for screening compounds for the biological activity. The fields of combinatorial chemistry and high-throughput screening matured throughout the early 1990s to meet up the challenges of modern pharmaceutical research. The Solid-phase synthesis (SPS) and parallel solution-phase synthesis methods have the potential to deliver hundreds of thousands of compounds in a relatively short period of time. Though, the emergence of such combinatorial organic chemistry methods has made the additional demand for new analytical methods to follow the course of chemical reactions and characterize the final products.
General area of organic synthesis:
1) Total synthesis:
A total synthesis is the complete chemical synthesis of the complex organic molecules from simple, commercially available (that is, petrochemical) or natural precursors. Total synthesis might be achieved either through a linear or convergent approach. In a linear synthesis - often sufficient for simple structures - some steps are carried out one after the other till the molecule is complete. The chemical compounds made up in each and every step are known as synthetic intermediates. For more complex molecules, a distinct approach might be preferable: convergent synthesis comprises the individual preparation of some 'pieces' (that is, key intermediates), which are then joined to form the desired product.
Robert Burns Woodward, who awarded the 1965 Nobel Prize for Chemistry for some total syntheses (example, his 1954 synthesis of strychnine), is regarded as the father of modern organic synthesis. A few latter-day illustrations comprise Wender's, Holton's, Nicolaou's and Danishefsky's synthesis of taxol.
Semi-synthesis or partial chemical synthesis is a kind of chemical synthesis which employs compounds isolated from the natural sources (example: plant material or bacterial or cell cultures) as starting materials. Such natural biomolecules are frequently large and complex molecules. This is different from total synthesis where large molecules are synthesized via a stepwise combination of small and low-priced (generally petrochemical) building blocks.
Semi-synthesis is generally employed whenever the precursor molecule is too structurally complex, too expensive or too hard to be produced via total synthesis. From the synthesis view-point, life is able of biosynthesizing structurally complex chemical compound. In several cases, by a small agricultural investment, a plant can be grown to generate chemical intermediates which chemical synthesis would struggle to generate. Explanation of such intermediates by synthetic chemistry can then cost-effectively give the complex final targets.
Drugs derived from the natural sources are generally produced via harvesting the natural source or via semisynthetic processes: one illustration is the semi-synthesis of LSD from ergotamine that is isolated from ergot fungus cultures. The commercial production of paclitaxel is as well based on the semi-synthesis.
Methodology is the methodical, theoretical analysis of the techniques applied to a field of study. It includes the theoretical analysis of the body of processes and principles related by a stream of knowledge. Generally, it encompasses concepts like paradigm, theoretical model, phases and qualitative or quantitative methods.
A methodology doesn't set out to give solutions - it is, thus, not similar as a method. Rather, a methodology offers the theoretical underpinning for understanding that method, set of methods, or so-called 'best practices' can be applied to particular case, for illustration, computing a particular result.
It has been stated as well as follows:
a) The analysis of principles of techniques, rules and hypothesizes used by a discipline.
b) The systematic study of methods which are can be or have been applied in a discipline.
c) The study or illustration of methods.
Importance of Organic Synthesis:
The Organic synthesis plays a significant role for medicine, chemistry, biochemistry, agriculture and other fields. In several cases the target molecule consists of an unusual structure whose characterization might advance understanding of different theoretical features of chemistry. Such a molecule might possess mainly unusual patterns of bonding, like a strained ring system or unique symmetry.
The heart of organic synthesis is designing synthetic routes to the molecule. Organic synthesis can be compared by architecture and construction, where the chemist should work out a synthetic route to a target molecule (that is, blueprint), then use a repertoire of organic reactions (that is, the 'tools') to complete the construction project. All along the manner, the synthetic chemist should make extensive utilization of analytical methods for purifying and characterizing the intermediate products and also the final product.
The easiest synthesis of a molecule is one in which the target molecule can be achieved via submitting a readily available starting material to a single reaction which transforms it to the desired target molecule. Though, in most of the cases the synthesis is not that straightforward; in order to transform a selected starting material to the target molecule, many steps which add, change or remove the functional groups and steps that build up the carbon atom framework of the target molecule might require to be done.
Stereo-selectivity can't be accomplished for all organic reactions; the nature of method of some reactions might not allow for the formation of one specific configuration of a chiral (that is, stereogenic) carbon center or one particular geometry (that is, cis versus trans) for a double bond or ring. Whenever stereo-selectivity can be accomplished in a reaction, it needs that the reaction proceeds through a geometrically defined transition state and that one or both of the reactants have a specific geometrical shape throughout the reaction.
The accomplishment of stereo-selectivity is a significant feature of organic synthesis, as generally a single stereoisomer of a target molecule is the desired goal of a synthesis. At times the target molecule includes a chiral (that is, stereogenic) carbon center; which is, it can exist as either of two possible enantiomers. The possible synthetic routes to the target molecule might not be selective for making a single enantiomer of the target molecule; each would make a racemic mixture. (+)-Dibenzoyl-D-tartaric acid monohydrate is employed as an intermediate in the organic syntheses. In various cases, such non-stereoselective synthetic routes to a molecule are acceptable.
However, whenever a synthesis of a single stereoisomer of a target molecule is needed, the stereo-selectivity of the reactions derived throughout the retro synthetic analysis would require to be considered. The growth of stereoselective reactions is the active area of research in organic synthesis.
Techniques applied in Organic Synthesis:
There are many methods which are often employed and practiced in the organic synthesis.
1) UV/Vis Spectroscopy: The organic molecules and functional groups are transparent in the part of electromagnetic spectrum that as UV and visible regions lie in the wavelengths from 190 to 800nm. As a result, absorption spectroscopy is of limited value in this range of wavelengths. Though, in some case we can derive valuable information from such regions of the spectrum. That information, whenever combined by the detail provided via IR and NMR spectra, can lead to important structure proposals.
2) Infra red (IR) spectroscopy: Nearly any compound having covalent bonds, whether organic or inorganic, absorbs different frequencies of electromagnetic radiation in the infra red region of the electromagnetic spectrum. This region lies at wavelengths longer than those related by visible light, that range from around 400 to 800 nm, however lies at wavelengths shorter than those related with microwaves that are longer than 1mm. For chemical aims, scientists are interested in the vibrational part of the infrared region. It comprises by the wavelengths between 2.5µm and 25µm. IR spectroscopy states us regarding the functional groups present in the molecule.
3) Nuclear magnetic resonance (NMR) Spectroscopy: NMR is the spectroscopic technique which is even more significant to the organic chemist as compare to IR spectroscopy. Most of the nuclei might be studied by NMR methods; however hydrogen and carbon are most generally available. While IR spectroscopy reveals the kinds of functional groups present in the molecule, NMR provides information regarding the number of magnetically dissimilar atoms of the kind being studied. Whenever hydrogen nuclei are studied, for illustration, one can find out the number of each of the different kinds of hydrogen nuclei and also acquire information concerning the nature of the immediate environment of each kind. Identical information can be found out for the carbon nuclei. The combination of IR and NMR data is often adequate to find out completely the structure of an unknown molecule.
4) Mass Spectrometry: Mass Spectrometry originated from the late year 1890s when J.J.Thomson found out the mass-to-charge ratio of the electron, and Wien studied magnetic deflection of anode rays and found out the rays were positively charged. Each and every man was honored by the Noble Prize later on. In the year 1912, the former scientist studied mass spectra of atmospheric gases and employed a mass spectrum to illustrate the existence of neon-22 in a sample of neon-20, thus establishing that elements could have isotopes. The earliest mass spectrometer was manufactured by A.J.Dempster in the year 1918. Nowadays, mass spectrometry is employed in different fields of life sciences.
5) Chromatography: Discovered in the year 1906 via a botanist, Mikhail Tsvet.
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