Vitamin B12 substances

If you think some of the synthesis problems at the end of this chapter are hard, try devising a synthesis of vitamin B12 starting only from simple substances you can buy in a chemical catalog. This extraordinary achievement was reported in 1973 as the culmination of a collaborative effort headed by Robert B. Woodward of Harvard University and Albert Eschenmoser of the Swiss Federal Institute of Technology in Zurich. More than 100 graduate students and postdoctoral associates contributed to the w ork, which took more than a decade. 

When the Woodward-Eschenmoser synthesis began, it was known from the work of Bernhauer et al.5 that cobyric acid (4), a naturally occurring substance, could be converted directly into vitamin B12. Thus, the synthetic problem was reduced to the preparation of cobyric acid, a molecule whose seventh side chain terminates in a carboxylic acid group and is different from the other side chains. Two strategically distinct and elegant syntheses of the cobyric acid molecule evolved from the combined efforts of the Woodward and Eschenmoser groups and both will be presented. Although there is naturally some overlap, the two variants differ principally in the way in which the corrin nucleus is assembled. 

Cobalt is an essential element for animals but not for plants, found in vitamin B12 and is utilized by micro-organisms. Vitamin B12, in common with a range of other organic substances can be taken up passively by plants. Plants products can therefore, contain considerable quantities of vitamin B12 although it is not essential for normal plant development (Mozafar 1994 Lundegardh and Martensson 2003). 

Cyanide is usually found in compounds (substances formed by joining two or more chemicals). Cyanide can interact with metals and other organic compounds (compounds that include carbon). Sodium cyanide and potassium cyanide are examples of simple cyanide compounds. Cyanide can be produced by certain bacteria, fungi, and algae, and is found in a number of foods and plants. In your body, cyanide can combine with a chemical (hydroxocobalamin) to form vitamin B12 (cyanocobalamin). In certain plant foods, including almonds, millet sprouts, lima beans, soy,... 

Vitamin B12 is a chemical substance containing cyanide that is beneficial to your body because it prevents anemia (iron-poor blood). The cyanide is bound in Vitamin B12 so that it does not serve as a source of cyanide exposure and cannot harm you. You can find more information on the harmful effects of cyanide in Chapter 2. 

Interest in the vitamin B12 catalyzed light assisted electrolysis directed to the preparation of fine chemicals has been well illustrated in the synthesis of some natural products. One typical example is the synthesis of the Queen substance of Apis mellifera which involves two efficient electrochemical C,C-bond-forming steps by addition to conjugated double and triple bonds (Scheme 4) [63]. 

Vitamin B12 (cobalamine) is one of the most complex low-molecular-weight substances occurring in nature. The core of the molecule consists of a tetrapyrrol system (corrin), with cobalt as the central atom (see p. 108). The vitamin is exclusively synthesized by microorganisms. It is abundant in liver, meat, eggs, and milk, but not in plant products. As the intestinal flora synthesize vitamin B12, strict vegetarians usually also have an adequate supply of the vitamin. 

A few substances are so large or impermeant that they can enter cells only by endocytosis, the process by which the substance is bound at a cell-surface receptor, engulfed by the cell membrane, and carried into the cell by pinching off of the newly formed vesicle inside the membrane. The substance can then be released inside the cytosol by breakdown of the vesicle membrane. Figure 1-5D. This process is responsible for the transport of vitamin B12, complexed with a binding protein (intrinsic factor) across the wall of the gut into the blood. Similarly, iron is transported into hemoglobin-synthesizing red blood cell precursors in association with the protein transferrin. Specific receptors for the transport proteins must be present for this process to work. 

One substance that has been found to be an essential requirement for the biosynthesis of DNA is the cobalt-containing vitamin B12 (42). Ever since this substance was first isolated and its structure determined, there has been a widespread search for the specific reactions that it mediates. The first such reaction was discovered by Barker, Weissbach, and Smyth (5), when they examined the enzymatic isomerization of glutamic acid to /3-methylaspartic acid. They were... 

The B-group is a heterogeneous collection of water-soluble vitamins, most of which function as co-enzymes or are precursors of co-enzymes. The B-group vitamins are thiamin, riboflavin, niacin, biotin, pantothenic acid, pyridoxine (and related substances, vitamin B6), folate and cobalamin (and its derivatives, vitamin B12). 

Covalent synthesis of complex molecules involves the reactive assembly of many atoms into subunits with aid of reagents and established as well as innovative reaction pathways. These subunits are then subjected to various reactions that will assemble the target molecule. These reaction schemes involve the protection of certain sensitive parts of the molecule while other parts are being reacted. Very complex molecules can be synthesized in this manner. A prime example of the success of this approach is the total synthesis of palytoxin, a poisonous substance found in marine soft corals (35). Other complex molecules synthesized by sequential addition of atoms and blocks of atoms include vitamin B12, the potentially anticancer KH-1 adenocarcinoma antigen, and epothilones A and B (36,143—145). 

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