Vitamin esterification reactions

A new preparation of the C g ketone, an important synthon for the synthesis of vitamin A had also been published by Valla et al. [71]. Hence p-ionone and acetonitrile were condensed in the presence of KOH, to afford the nitrile (80%, E/Z isomers 80/20). A Reformatsky reaction of ethyl bromoacetate with the nitrile provided the ethyl P-ionylideneacetoacetate in 70% yield. Subsequent reduction with NaBH4, followed by esterification (MeSC Cl) and desulfonation of the unstable... 

The acid chloride is useful for the isolation of low-niellinit alcohols reaction in pyridine gives an ester of lower solubility and higher melting point. For example, vitamin D (m,p. 82-84°) from fish liver oil concentrates was isolated by esterification with 3,5-dinitrobenzoyl chloride, and purification by chromatography and crystallization as the 3J5-dinitrobenzoate, ra.p. 132°. ... 

Sometimes reaction rates can be enhanced by using multifunctional reactors, i.e., reactors in which more than one function (or operation) can be performed. Examples of reactors with such multifunctional capability, or combo reactors, are distillation column reactors in which one of the products of a reversible reaction is continuously removed by distillation thus driving the reaction forward extractive reaction biphasing membrane reactors in which separation is accomplished by using a reactor with membrane walls and simulated moving-bed (SMB) reactors in which reaction is combined with adsorption. Typical industrial applications of multifunctional reactors are esterification of acetic acid to methyl acetate in a distillation column reactor, synthesis of methyl-fer-butyl ether (MTBE) in a similar reactor, vitamin K synthesis in a membrane reactor, oxidative coupling of methane to produce ethane and ethylene in a similar reactor, and esterification of acetic acid to ethyl acetate in an SMB reactor. These specialized reactors are increasingly used in industry, mainly because of the obvious reduction in the number of equipment. These reactors are considered by Eair in Chapter 12. 

Methylnaphthalene is commonly used as a feedstock in the production of vitamia K3 (menadione). Methylnaphthalene is oxidized to menadione with chromic or nitric acid, in a similar method to anthracene oxidation. Menadione is used as an intermediate in the production of vitamin Ki.To produce vitamin Ki, menadione is reduced with hydrogen on Pd/activated-carbon catalysts to mena-diol. Esterification of the two hydroxyl groups with acetic anhydride yields mena-diol diacetate, which is converted into the 1-monoacetate with ammonia. Vitamin Ki (phytomenadione) is produced by the reaction of 1-menadiol monoacetate with phytol, using a BF3/ether complex as catalyst, followed by hydrolysis and dehydrogenation. 

Lonza, a fine chemical manufacturer, has developed a biotechnological route, starting with 3-cyanopyridine to nicotinamide (also known as niacin or vitamin B3) (see Fig. 9.11). Conversions are based on enzymatic hydrolysis with nitrile hydratase from Rhodo-coccus bacteria or by bioconversion with living bacterial cells. The reactions are very specific, and the yields are quantitative. Novo-zyme has introduced an extremely thermostable lipase from the yeast Candida (Pseudozyma) antarctica (Novozyme 435), which is extremely suitable for carrying out specific esterifications in organic solvents. 

The addition of potassium cyanide to the acid (77) and subsequent acid (not, as before, alkaline) hydrolysis, led to a mixture of the cis- and transisomers from which the pure trans-isomer, forming the trans-diester (80) on esterification, was isolated by crystallization. Reduction of the keto group, Dieckmann cyclization of the hydroxydiester formed, and decarboxylation led to the Z-trans-C/D ketol (79). Resolution of the racemic diacid corresponding to the diester (80) by crystallizing its brucine salts and performing the reactions described above with the optical isomers obtained enabled the tZ-enantiomer of the ketol (79) to be obtained [898], this being identical with the product formed in the oxidation of vitamin D2 [899]. This enantiomer has also been used as the CD fragment in the synthesis of vitamin D (Scheme 90). 

There are two forms of the hydrolytic enzyme, one of which is specific for short chain esters like retinyl acetate, even though this ester does not occur naturally The other has maximum activity with retinyl palmitate as substrate but also hydrolyses other long chain esters. As in the hydrolysis of cholesteryl esters, the enzyme is not just a non-specific esterase, but has quite definite specificity for retinyl esters. In vitamin A deficiency, the activity of the enzyme increases one hundred fold. The esterification enzyme resembles the low energy cholesteryl esterase in that neither ATP nor coenzyme A appear to take part in the reaction nor are free fatty acids or acyl-CoA thiolesters incorporated into retinyl esters. One of the major problems in this area of research is to identify the acyl donor, which may be, as in plasma cholesteryl ester biosynthesis, a phospholipid. 

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