D-pantothenic acid

Figure 1 shows the structure of pantothenic acid ((R)-(+)-N-(2,4-dihydroxy-3,3 -dimethyl-1 -oxobuty 1-13-alanine). Only D(+)-pantothenic acid occurs naturally and is biologically active. The alcohol (R)-pantothenol (= (D)-panthenol) shows biological activity as well. 

D-(+)-Pantothenic acid calcium salt (A-[2,4-dihydroxy-3,3-dimethylbutyryl] P-alanine... 

D-(+)-Pantothenic acid calcium salt (A-[2,4-dihydroxy-3,3-dimethylbutyryI] p-alanine calcium salt) [137-08-6] M 476.5, m 195-196°, 200-201°, [a]20 +28.2° (c 5, H20). It forms needles on recrystn from MeOH, EtOH or isoPrOH (with 0.5mol of isoPrOH). Moderately hygroscopic. The... 

Antagonists of niacin include pyridine-3-sulfonie acid (in bacteria), 3-acetylpyridine, 6-aminonicctinamide, and 5-thiazole carboxamide. Synergists include vitamins Bj, B, B. B]). and D, pantothenic acid, folic acid, and soiualotrupliin (growth hormone). 

Fig. 8. Possible routes for the synthesis of D-pantothenic acid through the enzymatic transformation. PL, pantolactone KPL, ketopantolactone KPA, ketopantoic acid d-PA, D-pantoic acid KPaOEt, ethyl 2 -ketopantothenate KPaCN, 2 -ketopantothenonitrile D-PaOEt, ethyl D-pan-tothenate D-PaCN, D-pantothenonitrile...

During the course of studies on the microbial production of chiral intermediates for D-pantothenic acid [2,134,135], Shimizu and co-workers found that several micro-organisms, such as Fusarium, Brevibacterium and so on, produce a novel enzyme that catalyzes the hydrolysis of aldonate lactones or aromatic lactones [136, 137],... 

Biotechnological Production of D-Pantothenic Acid and its Precursor D-Pantolactone... 

D-Pantolactone (Figure 6.3.1) is an important intermediate in the production of d-pantothenic acid, also called vitamin B5. Deficiency of pantothenic acid can result in symptoms such as pathological changes of the skin and mucosa, disorders in the gastrointestinal tract and nervous system, organ changes, and hormonal disorders. Pantothenic acid is used mainly in feed for chicken and pigs and also as a vitamin supply in human nutrition. Its commercial form, the calcium salt, is produced worldwide on a multi-thousand ton scale. 

D-Pantothenic acid is also traditionally produced by chemical processes which involve efficient but troublesome and costly crystallization of diastereomeric salts of pantoate and chiral amines. After lactonization of the isolated D-pantoate, d-pantolactone is reacted with / -alanine to give D-pantothenate. Because the monovalent salts of pantothenic acid are highly hygroscopic, conversion into the calcium salt is essential for convenient formulation. The third class of synthetic processes for optically active compounds makes use of biotechnology. For natural com-... 

Fig. 6.3.3. Production of D-pantothenic acid by resolution of D,L-pantolactone by either a d- or an L-specific lactono-hyd rolase.

Several biotechnological synthetic methods for D-pantothenic add and its precursor D-pantolactone have been developed over the past 15 years. Although all have reached preparative scale and might result in cost-effective production processes, they differ considerably in their process characteristics - for example educts and space-time yields, especially when a fermentation and biotransformation are compared. Compared with the chemical process, the biotechnological processes reduce waste production and provide the possibility of a more environmentally friendly yet still competitive means of production of D-pantothenic acid. 

Nicotinamide D-Pantothenic acid (hemiCa salt) 6.10 11.90 Vitamin B12 0.0135... 

Product Glycidylbutyrate Butyl glucosides Styrene oxides Oligosaccharides D-pantothenic acid L-malic acid L-methionine L-valine R-mandelic acid L-Camitine Aspartame L-aspartate Cyclodextrins (S)-CPA 6-APA Cocoa Butter Acrylamide HFCS... 

A number of other important drug intermediates are produced at scale (>1000 kg/year) by biocatalysis including D-phenylglycine and D-(p-hydroxyphenyl)glycine for antibiotics, nicotinamide, 6-hydoxynicotinic acid, (R)-glycidol, and D-pantothenic acid. Many... 

The atom efficiency of a kinetic resolution is increased if the starting material is not an ester but a lactone. Indeed, kinetic resolutions of lactones are used on an industrial scale. Fuji/Daiichi Chemicals produces D-pantothenic acid on a multi-ton scale based on such a resolution. D-Pantolactone is hydrolysed at pH 7 by a hydrolase from Fusarium oxysporum yielding D-pantoic acid with an ee of 96% while L-pantoic acid was barely detectable. The immobilized Fusarium oxysporum cells were recycled 180 times and retained 60% of their activity, demonstrating the great stability of this catalytic system [47-50]. 

D-Pantoic acid is again lactonised and then converted into D-pantothenic acid, better known as vitamin B5 (Scheme 6.13). The remaining L-pantolactone can be racemised and recycled. Similar approaches based on L-specific lactonohydro-... 

Following these studies, D-pantothenic acid -glucopyranoside (95) was prepared by action of various /3-glucosidases [174]. Also a-glucoside of pantotheic acid was isolated, however, the... 

The normal situation seen with vitamins that have two or more stereoisomers is only one isomer is active. Thus a racemic (usually represented as d,D mixture contains 50%of the activity compared with an equimolar amount of the active isomer. Examples where only one isomer is active includes d-pantothenic acid, D-biotin, and D-ascorbic acid. 

Asymmetric reduction of ketopantoyl lactone is an effective biomimetic route to R-(- )-pantolactone, an intermediate in the synthesis of the important d-( + )-pantothenic acid (a component of vitamins B and of coenzyme A) ... 

R)-pantolactone (384) is in demand as a precursor to the vitamin (+)-D-Pantothenic acid further methods for obtaining this enantiomer... 

This asymmetric induction was used to obtain d-( — )-pantoyl lactone (7), the microbiological precursor to D-(-)-pantothenic acid (8). The key step, reduction... 

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