Vitamins discovery

Vitamin Discovery Isolation Chemical stmcture Synthesis... 

Vitamin Discovery/ isoiation isoiated from Active form Function... 

F. R. Frankenburg (2009) Vitamin discoveries and disasters. ABC-CLIO, Santa Barbara. 

Structural drawings of carbohydrates of this type are called Haworth formulas, after the British chemist Sir Walter Norman Haworth (St Andrew s University and the University of Birmingham) Early m his career Haworth contributed to the discovery that carbohydrates exist as cyclic hemiacetals rather than m open chain forms Later he col laborated on an efficient synthesis of vitamin C from carbohydrate precursors This was the first chemical synthesis of a vitamin and provided an inexpensive route to its prepa ration on a commercial scale Haworth was a corecipient of the Nobel Prize for chem istry m 1937... 

Deficiency Diseases. Not only did cereals make an important contribution to improving the general status of humankind, but they also were important dietary components of some groups of people who showed certain nutritional deficiencies. This observation led to the discovery of some of the vitamins. These deficiency diseases have been most prominently associated with use of rice, com, and wheat. 

The term vitamin is derived from vitamine, a word created ia 1911 (1) when it was beheved that the antiberiberi factor (thiamine) was an amine essential to the maintenance of life (vita). Later discoveries showed that not all vitamins ate amines. However, a form of the name has remained. 

Christiaan Eijkman medicine, physiology discovery of antineuritic vitamins... 

Albert Szent-Gynrgyi medicine, physiology discoveries ia connection with biological combustion processes, with special reference to vitamin C and catalysis of fumaric acid... 

Research lea ding to the discovery of vitamin C began in 1907 when it was observed by Axel Holst and Theodor Ern hlich that guinea pigs were as susceptible to scurvy as humans and that the disease could be produced experimentally in these animals (8). These findings led to the development of an assay for the biological deterrnination of antiscorbutic activity of food products (9). 

In 1933, R. Kuhn and his co-workers first isolated riboflavin from eggs in a pure, crystalline state (1), named it ovoflavin, and deterrnined its function as a vitamin (2). At the same time, impure crystalline preparations of riboflavin were isolated from whey and named lyochrome and, later, lactoflavin. Soon thereafter, P. Karrer and his co-workers isolated riboflavin from a wide variety of animal organs and vegetable sources and named it hepatoflavin (3). Ovoflavin from egg, lactoflavin from milk, and hepatoflavin from Hver were aU. subsequently identified as riboflavin. The discovery of the yeUow en2yme by Warburg and Christian in 1932 and their description of lumiflavin (4), a photochemical degradation product of riboflavin, were of great use for the elucidation of the chemical stmcture of riboflavin by Kuhn and his co-workers (5). The stmcture was confirmed in 1935 by the synthesis by Karrer and his co-workers (6), and Kuhn and his co-workers (7). 

Animals cannot synthesize vitamin A-active compounds and necessary quantities are obtained by ingestion of vitamin A or by consumption of appropriate provitamin A compounds such as P-carotene. Carotenoids are manufactured exclusively by plants and photosynthetic bacteria. Until the discovery of vitamin A in the purple bacterium Halobacterium halobium in the 1970s, vitamin A was thought to be confined to only the animal kingdom (56). Table 4 Hsts RDA and U.S. RDA for vitamin A (67). 

The discovery that vitamin was metabolized to biologically active derivatives led to a significant effort to prepare 25-hydroxy vitamin and, subsequendy, the 1 a-hydroxy and 1,25 dihydroxy derivatives. Initial attempts centered around modification of steroidal precursors, which were then converted to the D derivatives by conventional means. 

The discovery that vitamin D metaboUtes play a much larger biochemical role than just maintaining calcium homeostasis has stimulated a number of groups around the world to develop more economical chemical syntheses for the vitamin D metaboUtes and analogues, which might be useful ki studykig and treating D -related diseases and conditions. Many of these methods are reviewed ki References 139 and 140. 

The discovery of folic acid as a vitamin and the recognition of its versatile modes of action in biological systems focused early attention on simple synthetic pteridines with... 

In the post-World War II years, synthesis attained a different level of sophistication partly as a result of the confluence of five stimuli (1) the formulation of detailed electronic mechanisms for the fundamental organic reactions, (2) the introduction of conformational analysis of organic structures and transition states based on stereochemical principles, (3) the development of spectroscopic and other physical methods for structural analysis, (4) the use of chromatographic methods of analysis and separation, and (5) the discovery and application of new selective chemical reagents. As a result, the period 1945 to 1960 encompassed the synthesis of such complex molecules as vitamin A (O. Isler, 1949), cortisone (R. Woodward, R. Robinson, 1951), strychnine (R. Woodward, 1954), cedrol (G. Stork, 1955), morphine (M. Gates, 1956), reserpine (R. Woodward, 1956), penicillin V (J. Sheehan, 1957), colchicine (A. Eschenmoser, 1959), and chlorophyll (R. Woodward, 1960) (page 5). ... 

Riboflavin was first isolated from whey in 1879 by Blyth, and the structure was determined by Kuhn and coworkers in 1933. For the structure determination, this group isolated 30 mg of pure riboflavin from the whites of about 10,000 eggs. The discovery of the actions of riboflavin in biological systems arose from the work of Otto Warburg in Germany and Hugo Theorell in Sweden, both of whom identified yellow substances bound to a yeast enzyme involved in the oxidation of pyridine nucleotides. Theorell showed that riboflavin 5 -phosphate was the source of the yellow color in this old yellow enzyme. By 1938, Warburg had identified FAD, the second common form of riboflavin, as the coenzyme in D-amino acid oxidase, another yellow protein. Riboflavin deficiencies are not at all common. Humans require only about 2 mg per day, and the vitamin is prevalent in many foods. This vitamin... 

In a study of the effect of nutrition on reproduction in the rat in the 1920s, Herbert Evans and Katherine Bishop found that rats failed to reproduce on a diet of rancid lard, unless lettuce or whole wheat was added to the diet. The essential factor was traced to a vitamin in the wheat germ oil. Named vitamin E by Evans (using the next available letter following on the discovery of vita-... 

The important biological role of the isobacteriochlorins has decisively influenced the development of synthetic approaches leading to the isobacteriochlorin class of compounds. All of the naturally occurring isobacteriochlorins contain geminally dialkylated structural parts in the saturated pyrrole rings, which require special approaches for their synthesis. Until the discovery of siroheme and sirohydrochlorin, this structural element could only be found in vitamin B,2. Using the synthetic potential, which was invented during numerous syntheses of... 

Ragsdale, S. W. Kumar, M. Zhao, S. Menon, S. Seravalli, J. Doukov, T. Discovery of a Bio-organometallic Reaction Sequence Involving Vitamin B12 and Nickel/ Iron-Sulfur Clusters Wiley-VCH Weinheim, Germany, 1998. 

Possibly the most significant discovery in the metabolism of aromatic azo compounds had implications that heralded the age of modem chemotherapy. It was shown that the bactericidal effect of the azo dye Prontosil in vivo was in fact due to the action of its transformation product, sulfanilamide, which is an antagonist of 4-aminobenzoate that is required for the synthesis of the vitamin folic acid. Indeed, this reduction is the typical reaction involved in the first stage of the biodegradation of aromatic azo compounds. 

Lenhert and Hodgkin (15) revealed with X-ray diffraction techniques that 5 -deoxyadenosylcobalamin (Bi2-coenzyme) contained a cobalt-carbon o-bond (Fig. 3). The discovery of this stable Co—C-tr-bond interested coordination chemists, and the search for methods of synthesizing coen-zyme-Bi2 together with analogous alkyl-cobalt corrinoids from Vitamin B12 was started. In short order the partial chemical synthesis of 5 -de-oxyadenosylcobalamin was worked out in Smith s laboratory (22), and the chemical synthesis of methylcobalamin provided a second B 12-coenzyme which was found to be active in methyl-transfer enzymes (23). A general reaction for the synthesis of alkylcorrinoids is shown in Fig. 4. 

Ships that carried beer tended to be less affected than those that carried water and spirits. Presumably, the beer contained some vitamin C, possibly from the habit of dry hopping , i.e. adding a few hop cones to each barrel. Eventually, it was found that lemon or lime juice every day could prevent scurvy. The admiralty waited fifty years before they applied the discovery and then insisted that all British ships carried lime juice. 

There is, moreover, the field of hypervitaminoses, which has been explored for the fat-soluble vitamins, but hardly touched in the water-soluble vitamins. The production of combined system disease by folic acid therapy of pernicious anemia belongs to this group, but many more instances wait to be recognized. The indiscriminate use of polyvitamin preparations by poorly informed clinicians is bound to mask such states and to delay their discovery. Also, the use of flushing doses of vitamins in diagnostic tests may cause acute hypervitaminoses. 

Where die connection between a vitamin and a disease is less transparent, a wide field remains open for the discovery of meaningful correlations between vitamin content of body fluids and tissues and physiologic or pathologic events. 

A healthy diet with proper nutrition is essential for maintaining good overall health. Since the discovery of vitamins earlier in this century, people have routinely been taking vitamin supplements for this purpose. The Recommended Dietary Allowance (RDA) is a frequently used nutritional standard for maintaining optimal health. The RDA specifies the recommended amount of a number of nutrients for people in different age and sex groups. The National Research Council s Committee on Diet and Health has proposed a definition of the RDA to be that amount of a nutrient which meets the needs of 98% of the population. 

In December 1929, Frederick Gowland Hopkins shared the Nobel Prize in Medicine or Physiology, "for his discovery of the growth-stimulating vitamins."... 

In the mid 1920 s, Funk became embroiled in a controversy over the discovery (and the discoverer) of the vitamines, or vitamins as they were then known. (8, % JO) He gave some credit to Hopkins for his early endeavors but refused to acknowledge Hopkins priority. This episode bears strongly upon remarks made by Hopkins in his Nobel Address of 1929 wherein he discussed Funk s work as well as McCollum s and that of Osborne and Mendel. 

It seems to us that you attach too much importance to the quantitative relations of milk as a source of the water-soluble vitamine. Even though larger quantities of milk may ultimately be demonstrated to be necessary than your original experiments indicated, we are sure that no one will ever think of criticizing your early work on that score. The essential importance of your discovery is in no way affected.. ..Pioneers in such fields of investigation are not expected to settle quantitative limits at the outset of such discoveries. 

Earlier, I mentioned that Casimir Funk had raised the issue of priority in the discovery of the vitamins. Hopkins did not enter into the debate at the time but he did devote a significant part of his Nobel Address to Funk and his contributions to the vitamin hypothesis. With respect to the other principals involved in the early episodes of vitamin research, it is appropriate to see what Hopkins said about them in Stockholm on that December day in 1929- His comments afford one more illustration of both the clarity and confusion that dominated his 1912 paper. 

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