Pantothenic acid analogs

Spry, C., Chai, C. L., Kirk, K., and Saliba, K. J. (2005). A class of pantothenic acid analogs inhibits Plasmodium falciparum pantothenate kinase and represses the proliferation of malaria parasites. Antimicrob. Agents Chemother. 49, 4649-4657. 

Several pantothenic acid analogs inhibit those reactions that require coenzyme A (acetylation of sulfanilamide and acetylcholine synthesis). Among these anti-... 

The D(+)-pantothenic acid analog D(+)-panthenol is a provitamin of B5 which is converted into pantothenic acid in the body. D(+)-Panthenol is used for cosmetic purposes. 

Pantothenic acid analog (Non>nitrogenous acid moiety, all joined to -alanine)... 

Attachment of phosphopantetheine to proteins is catalyzed by a phosphotransferase that utilizes CoA as the donor. A phosphodiesterase removes the phosphopantetheine, providing a turnover cycle.15, 5b A variety of synthetic analogs have been made.4 16 The reactive center of CoA and phosphopantetheine is the SH group, which is carried on a flexible arm that consists in part of the (3-alanine portion of pantothenic acid. A mystery is why pantoic acid, a small odd-shaped molecule that the human body cannot make, is so essential for life. The hydroxyl group is a potential reactive site and the two methyl groups may enter into formation of a "trialkyl lock" (p. 485), part of a sophisticated "elbow" or shoulder for the SH-bearing arm. 

Topical dexpanthenol, a stable alcoholic analog of pantothenic acid with good skin penetration, acts like a moisturizer, improves stratum corneum hydration, reduces transepidermal water loss, and maintains skin softness and elasticity. In wound-healing activation of fibroblast proliferation has been observed in vitro and in vivo with dexpanthenol concomitantly with increased elastic and solid tissue regeneration. In skin irritation pretreatment with dexpanthenol resulted in less damage to the stratum corneum barrier, while adjuvant treatment improved the symptoms of dryness, roughness, scaling pruritus, erythema, and erosions considerably. The topical application is well-tolerated with a minimal risk of skin irritation or sensitization.129-132... 

Coenzyme A analogs are best synthesized by a combined chemical and enzymatic method. Pantothenic acid was first converted to the thiophenol ester and then the terminal OH group was phosphorylated via the dimethyl phosphate triester. Thiol exchange with ethanedithiol gave the a-thiol—phosphate. This compound was first enzymatically combined with ATP and then phosphorylated at 3-OH (Scheme 7.3.8). A wide range of CoA analogs is thus accessible (Martin and Drueckhammer, 1992). 

Pantolactone, an important intermediate for the synthesis of pantothenic acid (a constituent of Coenzyme A), is commercially available in only one optically active form. The (/ )-(— )-enantiomer currently sells for slightly less than 1.00 per gram. ( S)-( + )-Pantolactone (257) must be synthesized, and it is readily accessible from L-malic acid via the 3,3-dimethyl analog 231a [80]. Selective hydrolysis of the 1-ester furnishes the monoacid 256. Reduction of the 4-ester with L-Selectride followed by lactonization then gives 257 in 40% overall yield starting from dimethyl (5)-malate (2 231a 256 —> 257). 

Vitamin B5 or pantothenic acid is a water soluble vitamin, which is mainly produced by chemical routes. Pantothenic acid is required for normal skin function as it leads to formation of coenzyme Q and is involved in carbohydrate, protein, and lipid metabolism. Dex-panthenol, an alcoholic analog of pantothenic acid is more stable and has good skin penetration than pantothenic acid. Dexpanthenol is mainly used for topical application on skin and serves as good moisturizer and thus improves the cosmetic appearance of skin. It has mild skin inflammatory activity, but is well tolerated by skin. Pantothenic acid improves wound healing, epidermal regeneration, and reduces scarring also. So, pantothenic acid itself can be used in various skin care formulations. Pantothenic acid is used in hair care formulation as it hydrates the hair and protects the hair fiom chemicals and UV rays. ... 

Panthenol, pantetheine, and pantetheine are analogs of pantothenic acid all have vitamin B5 activity. 

Samples of DL-panthenol and OL-pantolactone are converted to 3,5-dinitrophenyl carbamates in the same way as pantothenic acid, but without esterification. 3,5-Dinitrobenzoyl esters of these substances are prepared analogously as the... 

Two approaches are currently used for the preparation of volatile derivatives of the vitamin. The first approach is mostly based on the conversion of pantothenic acid and/or panthenol to acetyl (72) or trimethylsilyl derivatives (73). A simpler and more convenient approach for most applications seems to be the procedure based on the hydrolysis of the vitamin in acidic medium and analysis of the hydrolysis products. Pantothenic acid, its salts, and coenzyme A as well as its analogs undergo acid hydrolysis with formation of P-alanine and pantolactone. Panthenol breaks down to 3-amino-l-propanol (P-alanol) and pantolactone. For instance, P-alanine can be analyzed as the corresponding jv-trifluoroacetyl methyl ester or AMrifluoroacetyl butyl ester. Pantolactone is sufficiently volatile to be amenable to direct GLC (23,76,77), but it can also be analyzed as the corresponding trimethylsilyl ether, trifluoroacetyl, or isopropylurethane derivative (5,78). 

Currently employed HPLC methods for pantothenic acid and/or pantothenates have been applied solely to pharmaceuticals and simple matrices such as fortified infant formulas, whereas assays of coenzyme A and its acyl analogs have also been successfully performed on animal tissues. In the last few years, chiral stationary phases have been developed for optical resolution of pantothenic acid and related compounds by HPLC, and also HPLC-MS has become a promising technique. However, the newly developed HPLC procedures still require increased sensitivity and selectivity to make them applicable for the analysis of the total vitamin content in complex matrices such as foods and feeds. 

Table XIV records the effects with various analogs of pantothenic acid, when the non-nitrogenous portion is varied by condensing different hydroxy acids with /3-alanine. Only very slight activity is found with any of these compounds, showing that even slight modifications of the molecular structure very greatly decrease the biological activity. The same general picture is found with higher animals for which pantothenic acid has metabolic importance.

Since the antibiotin factor does not inhibit those bacteria which synthesize biotin, the antibiotin factor appears to combine only with the externally supplied biotin and cannot penetrate effectively to the sites of biotin synthesis and utilization. This is analogous to the findings with the synthetic inhibitory growth factor analogs (e.g., pyrithiamin and thiamin, pantoyl taurine and pantothenic acid, pyridine-2-sulfonamide and nicotinamide) where the inhibitory action is largely confined to those otgan-isms which do not synthesize the growth factor. 

The stability of pantothenic add in aqueous solutions depends greatly on the pH value. The vitamin is most stable in weakly acidic (pH 4 5) solutions, but in acidic and alkaline media the amide Hnkage is hydrolysed and pantothenic add yields pantoic add (or its salt) and fl-alanine. The enzyme pantothenase of some baderia specifically cleaves pantothenic add into the same products. In acidic solutions, pantoic acid spontaneously dehydrates to form lactone, (R)-2-hydroxy-3,3-dimethylbutano-4-lactone, which is called pantoyllactone or pantolactone (5-73). Analogously, products of panthenol hydrolysis are pantoic add... 

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