Vitamin crystallization

In animals found vitamin crystals In the renal tubules of anurlc rats that received 0.6 g/kg (Ip) (Unna and Greslln, 1942). 

Two molecules of vitamin A are formed from one molecule of -carotene. Vitamin A crystallizes in pale yellow needles m.p. 64 C. It is optically inactive. It is unstable in solution when heated in air, but comparatively stable without aeration. Vitamin A is manufactured by extraction from fish-liver oils and by synthesis from / -ionone. The role of vitamin A in vision seems to be different from its systemic function. See also relincne and rhodopsin. 

C63H90C0N14O14P. Dark red crystals. Vitamin has been prepared synthetically. 

While a number of proteins have been crystallized in this manner, the majority of studies have focused on a robust system comprising the tetrameric protein streptavidin and the vitamin biotin. The choice of this system is primcirily motivated by the strong bond between biotin and streptavidin (having an association equilibrium constant, Ka Tbe binding properties were recently... 

Fine chemical companies are generally either small and privately held or divisions of larger companies, such as Eastman Fine Chemicals (United States) and Lonza (Switzerland). Examples of large public fife science companies, which market fine chemicals as a subsidiary activity to their production for captive use, are Hoffmann-La Roche, Sandoz, and Boehringer Ingelheim, which produce and market bulk vitamins and liquid crystal intermediates, dyestuff intermediates, and bulk active ingredients, respectively. Table 3 fists some representative companies having an important fine chemical business. 

As a result of having two chiral centers, four stereoisomers of ascorbic acid are possible (Table 1) (Fig. 2). Besides L-ascorbic acid (Activity = 1), only D-araboascorbic acid (erythorbic acid (9)) shows vitamin C activity (Activity = 0.025-0.05). The L-ascorbic acid stmcture (1) in solution and the soHd state are almost identical. Ascorbic acid crystallizes in the space group P2 with four molecules in the unit cell. The crystal data are summarized in Table 2. 

In the human market, oral and parenteral dosage forms are prepared from the crystal. However, because of the extremely high potency, more dilute (0.1—10%) forms are avabable. These include dilutions with mannitol, triturations on dicalcium phosphate or resins, and spray-dried forms. Prices for these forms are driven by that of the crystal, which in early 1996 was ca 9.50/gram (95). Prices for the vitamin have risen during the first half of the 1990s. However, Htde growth in price beyond inflation is anticipated. 

Bunal in 1932 used x-ray crystallography to demonstrate that many of the preparations described in the Hterature were mixtures and that vitamin D2 was one crystal stmcture. 

The solvent is then evaporated, and the unconverted sterol is recovered by precipitation from an appropriate solvent, eg, alcohol. The recovered sterol is reused in subsequent irradiations. The solvent is then evaporated to yield vitamin D resin. The resin is a pale yeUow-to-amber oil that flows freely when hot and becomes a brittie glass when cold the activity of commercial resin is 20 30 x 10 lU/g. The resin is formulated without further purification for use in animal feeds. Vitamin D can be crystallized to give the USP product from a mixture of hydrocarbon solvent and ahphatic nitrile, eg, benzene and acetonitrile, or from methyl formate (100,101). Chemical complexation has also been used for purification. 

Canthaxanthin crystallines from various solvents as brownish violet, shiny leaves that melt with decomposition at 210°C. As is the case with carotenoids in general, the crystals are sensitive to light and oxygen and, when heated in solution or exposed to ultraviolet light or iodine, form a mixture of cis and trans stereoisomers. Consequentiy, crystalline canthaxanthin should be stored under inert gas at low temperatures. Unlike the carotenoid colorants P-carotene and P-apo-8 -carotenal, canthaxanthin has no vitamin A activity. It is chemically stable at pH 2—8 (the range normally encountered in foods) and unaffected by heat in systems with a minimal oxygen content. 

The dry crystals are stable for months in the dark, but aqueous solns decompose on exposure to VIS or UV light or alkaline CN", but stable in the dark at pH 6-7. The vitamin is inactivated by strong acids or alkalies. [Barker et al. J Biol Chem 235 480 1960 see also Vitamin B/2 (Zagalak and Friedrich Eds) W de Gruyter, Berlin 1979.]... 

Vitamin K3 (2-methyl-l,4-naphthoquinone, Menadione, Menaphthone) [58-27-5] M 172.2, m 105-106", 105-107". Recrystd from 95% EtOH, or MeOH after filtration. Bright yellow crystals which are decomposed by light. Solubility in EtOH is 1.7% and in C6H6 it is 10%. It IRRITATES the mucous membranes and skin. [Fieser J Biol Chem 133 391 1940.]... 

On the other hand, as a result of participation of a neighboring group, complete or predominant retention of configuration takes place in many reactions of hy-droxylic compounds with DAST A number of examples have been reported in the field of steroids [727, 729], m the conversion of vitamins D into fluoro vitamins D [745], and in the fluormation of liquid crystals [146] (equation 72]... 

After standing for several hours a small amount of precipitate (about 2 to 3 mg) was formed and was then separated from the solution. This solution was diluted with an additional 2 ml of acetone and again allowed to stand for several hours. During this time about 4 to 5 mg of noncrystalline precipitate formed. This solid was separated from the solution and an additional 2 ml of acetone was added to the solution. On standing, vitamin began to crystallize in the form of red needles. After standing for 24 hours, the crystalline material was separated, yield 12 mg. By further dilution of the mother liquor with acetone additional crystalline precipitate formed (from U.S. Patent 2,738,302). 

After stirring for 2 hours at room temperature, the mass of vitamin A acid has crystallized out. It is sharply filtered off by suction and washed with a little ice-cold isopropanol. From the filtrate, a further small amount of mainly all trans vitamin A acid crystallizes out upon the addition of water. The filter cake is suspended in 600 parts of water and stirred for 4 hours at room temperature it is filtered by suction and the product washed with water. It is dried in vacuo at 40° to 50°C and 115 parts of vitamin A acid are obtained. The melting point lies between 146° and 159°C. 

The mixture of the all trans and mainly 9,10-cis vitamin A acid may be separated by fractional crystallization from ethanol. All trans vitamin A acid has a melting point of 180° to 182°C and 9,10-cis vitamin A acid, which crystallized in the form of pale yellow fine needles collected into clusters, has a melting point of 189° to 190°C. 

When dried in an oven, hydrated silica loses its water and becomes a desiccant (a substance that attracts water from the air). You find little packets of silica gel crystals in containers whose contents would be damaged by condensing moisture, such as vitamin bottles, consumer electronics, pepperoni, or leather products. 

There are numerous abnormalities of cysteine metabolism. Cystine, lysine, arginine, and ornithine are excreted in cystine-lysinuria (cystinuria), a defect in renal reabsorption. Apart from cystine calculi, cystinuria is benign. The mixed disulfide of L-cysteine and L-homocysteine (Figure 30-9) excreted by cystinuric patients is more soluble than cystine and reduces formation of cystine calculi. Several metabolic defects result in vitamin Bg-responsive or -unresponsive ho-mocystinurias. Defective carrier-mediated transport of cystine results in cystinosis (cystine storage disease) with deposition of cystine crystals in tissues and early mortality from acute renal failure. Despite... 

P212121 Z = 4 D, = 1.362 R = 0.162 for 2112 intensities. The structure is very similar to that found308 for air-dried vitamin B12 crystals. Two water molecules move into phosphate oxygen-atom positions when the phosphate in the precursor is removed, and one acetamido group in contact with these water molecules in the vitamin is rotated out of the way in the phosphate. The disposition of the a-D-glycosyl bond between the D-ribosyl group and the 5,6-dimethylbenzimidazole is anti (—45°), and the conformation of the D-ribosyl group is 2T3 (P = 352.1 rm = 47.1). The orientation about the exocyclic, C-4 -C-5 bond is g+ (53°). 

A surfactant is a surface-active agent that is used to disperse a water-insoluble drug as a colloidal dispersion. Surfactants are used for wetting and to prevent crystal growth in a suspension. Surfactants are used quite extensively in parenteral suspensions for wetting powders and to provide acceptable syringability. They are also used in emulsions and for solubilizing steroids and fat-soluble vitamins. 

In 1958 Barker (20) isolated a red, heat stable, light labile, cofactor which was required for the metabolism of glutamate in cell-extracts of Clostridium tetanomorphum. Subsequently this cofactor was crystallized. X-ray crystallography identified Barker s cofactor as the coenzyme form of Vitamin B12 (15, 21). 

D-Pantolactone and L-pantolactone are used as chiral intermediates in chemical synthesis, whereas pantoic acid is used as a vitamin B2 complex. All can be obtained from racemic mixtures by consecutive enzymatic hydrolysis and extraction. Subsequently, the desired hydrolysed enantiomer is lactonized, extracted and crystallized (Figure 4.6). The nondesired enantiomer is reracemized and recycled into the plug-flow reactor [33,34]. Herewith, a conversion of 90-95% is reached, meaning that the resolution of racemic mixtures is an alternative to a possible chiral synthesis. The applied y-lactonase from Fusarium oxysporum in the form of resting whole cells immobilized in calcium alginate beads retains more than 90% of its initial activity even after 180 days of continuous use. The biotransformation yielding D-pantolactone in a fixed-bed reactor skips several steps here that are necessary in the chemical resolution. Hence, the illustrated process carried out by Fuji Chemical Industries Co., Ltd is an elegant way for resolution of racemic mixtures. 

Figure 13 (Plate 9). Crystal structure of the BtuC2D2 complex involved in the uptake of vitamin Bi2. Two copies of the polytopic integral membrane protein BtuC and of the ATPase subunit BtuD are shown, together with bound ATP (reproduced by permission of K. Locher). For more details see the text...

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