L-Ascorbic and D-isoascorbic acids

S Wongyai. Separation of L-(+)-ascorbic and D-(—)-isoascorbic acids on multimodal phenylpropanolamine-coated silica. Chromatographia 38 609-612, 1994. 

Table VI. Proton—Proton Coupling Constants and ASe,( for L-Ascorbic and D-Isoascorbic Acids...

The synthesis of 3,4-0-isopropylidene-L- and -o-erythrulose from L-ascorbic-and D-isoascorbic acids, respectively, proceeding through the corresponding protected tetritols, is covered in Chapter 2. The syntheses of natural and modified trapoxins and (+)-lanomycin by way of suitably protected tetritol derivatives, and... 

Various furanone chirons such as (22)-(24), and their C-5 epimers, have been prepared in optically-pure form from the dibromide (25) and its C-5 epimer these in turn are easily accessible from L-ascorbic and D-isoascorbic acids. 2 Baeyer-Villiger oxidation of levoglucosenone leads to the formation of the... 

Efficient routes have been described for the synthesis of butenolide (13), its L-threo-isomer. and related compounds from L-ascorbic and D-isoascorbic acids. 1 ... 

E.S.H.E. Ashry, K.F. Atta, S. Aboul-Ela, R. Beldi, MAOS of quinoxalines, conjugated pyrazolylquinoxalines and fused pyrazoloquinoxaUnes from L-ascorbic and D-isoascorbic acid, J. Carbohydr. Chem. 26 (2007) 1-16. 

L-ASCORBIC and D-ISOASCORBIC ACIDS CHIRON SOURCES FOR I -SECO-NUCLEOSIDES/TIDES, PHOSPHONATES, AND OTHER MOLECULES OF BIOLOGICAL INTEREST... 

In addition to providing easy access to l, 2 -5 co-nucleosides, -nucleotides, and phosphonate isosteres, L-ascorbic and D-isoascorbic acids proved to be useful in the preparation of equally attractive chirons that can be incorporated into other molecules of biological interest. Diol 6b is particularly attractive since it represents an easy entry into selectively protected erythritols. Having the R- and S-chiralities, access to both R- and 5-... 

R. Saibaba, M.S.P. Sarma, and E. Abushanab, The Chemistry of L-ascorbic and D-isoascorbic acids. 3 Efficient syntheses of pure R- and S- 1,2-0-isopropylidene-1,2,4-butanetriols, Synth. Commun. 9 30V (1989). 

C. Vargeese and E. Abushanab, Chemistry of L-ascorbic and D-isoascorbic acids. 

NMR Spectroscopy and the Conformations of L Ascorbic Acid and D-Isoascorbic Acid in Aqueous Solution... 

L-Ascorbic acid and D-isoascorbic acid in lemon, pineapple, sunkist, spinach... 

The synthesis of 2-deoxy-L-ascorbic acid has been described/ and the dipole moment of L-ascorbic acid in dioxane has been calculated by using Guggenheim Theory . 0-Benzyl ether and -benzylidene acetal derivatives of L-ascorbic acid and D-isoascorbic acid have been found to epimerize partly to the corresponding derivatives of L-isoascorbic acid and D-ascorbic acid, respectively, on treatment with triisobutylaluminium. The synthesis of [l- C]- and [2- C]-L-ascorbic acid by application of the KCN chain-extension to suitable compounds has been outlined. ... 

Figure 9.11 The diastereoisomers L-ascorbic acid (ascorbic acid) and D-isoascorbic acid...

The basic biologically active compound is ascorbic acid. Of the four possible stereoisomers (asymmetric carbons C-4 and C-5), the activity of vitamin C is seen only in L-ascorbic acid h-threo-hex-2-enonic acid 1,4-lactone formerly called ceritaminic acid, 2-keto-L-gulonic acid, L-xy/o-hex-2-ulosonic acid and later L-xylo-ascorbic acid). The D-isomer of ascorbic acid (n-xy/o-ascorbic acid) and the second pair of enantiomers, known as l- and d-isoascorbic acids (5-106 to 5-109), do not show vitamin C activity. Previously, these acids, which are y-lactones of l- and v-erythro-hex-2-enonic acids, were known as l- and o-erythorbic acids or L- and D-arabino-ascorbic acids. 

Tsao, C.S. and Salimi, S.L., Differential determination of L-ascorbic acid and D-isoascorbic acid by reversed-phase high-performance liquid chromatography with electrochemical detection, J. Chromatogr., 245(3), 355-358, 1982. 

Pappenberger G, Hohmann HP (2014) Industrial production of L-ascorbic acid (vitamin C) and D-isoascorbic acid. Adv Biochem Eng Biotechnol 143 143-188 Park C, Moon JY, Cokic P, Webster DA (1996) Na -translocating cytochrome bo terminal oxidase from Vitreoscilla some parameters of its Na" pumping and orientation in synthetic vesicles. Biochemistry 35 11895-11900... 

The novel tetrahydrofuran building blocks 97 and 98 have been prepared from L-ascorbic acid and D-isoascorbic acid respectively, and l,4 3,6-dianhydro-D-mannitol provides access to the ting and/or side chain-functionalized tetrahydrofurans 99-10l/ All of these units have obvious potential in synthesis and the value of dihydrofuran 100 has been illustrated by its... 

As aforementioned, derivatives of Vitamin C and their analogs can function as hyaluronidase inhibitors. In particular L-ascorbic acid-6-hexadecanoate is a potent inhibitor (A. Botski, et al., pers. commun.). Vitamin C itself, D-isoascorbic acid, and dehydroascorbic acid are also inhibitors 262 Thus, some of the ability of Vitamin C to enhance HA deposition may be attributed to its inhibiton of hyaluronidase. 

L-ascorbic acid (Figure 9-9) is a lactone (internal ester of a hydroxycarboxylic acid) and is characterized by the enediol group, which makes it a strongly reducing compound. The D form has no biological activity. One of the isomers, D-isoascorbic acid, or erythorbic acid, is produced commercially for use as a food additive. L-ascorbic acid is readily and reversibly oxidized to dehydro-L-ascorbic acid (Figure 9-10), which retains vitamin C activity. This compound can be further oxidized to diketo-L-gulonic acid, in a... 

The mean values of the L-ascorbic acid molecules and of D-isoascorbic acid are given for comparison. The values for Ca L-ascorbate dihydrate are weighed means of Refs. IS and 13. 

We thank J. Dadok at the Camegie-Mellon NMR Facihty for Biomedical Studies for help in obtaining the 600-MHz NMR data, and National Institutes of Health for support of the Facility. We also thank Thomas C. Crawford and Glenn C. Andrews of Pfizer, Incorporated, for samples of 5-D-L-ascorbic acid and 5-D-D-isoascorbic acid and the Kansas State Agricultural Experiment Station for support of the campus NMR facility. 

Three stereoisomers of L-ascorbic acid were also bioassayed using the tobacco hornworm (Table I). Configurational changes at C4 and C5 aflFected activity and indicated that the geometry of C5 was more critical for activity than that of C4. The enantiomer, D-ascorbic acid, had approximately 40% activity, while the C5 epimer, D-isoascorbic acid, had 10% activity. The relative potency of those isomers is reversed in vertebrate and invertebrate animals. With D-isoascorbic, 2-10% activity in other insects was reported (20-22), but this compound did not promote development of the cotton leafworm (23). L-Isoascorbic acid had no activity in the hornworm or guinea pig. 

L-ascorbic acid, D-isoascorbic acid, and L-dehydroascorbic acid inhibited progeny by producing diet nutritionally deficient in protein (browning)... 

Condensation of o-phenylenediamine with methylglyoxal, aldohexoses and aryl or alkyl acyloins gave the corresponding quinoxalines 76. Indoloquinoxalines were obtained from isatin. Carbethoxymethylation of isatin and then reaction with o-phenylenedimine gave the respective indoloquinoxalines 77, whereas hydrazide was condensed with aromatic aldehydes and monosaccharides. L-Ascorbic acid or D-isoascorbic acid were oxidized with iodine and then reacted with o-phenylenediamine and phenylhydrazine to give quinoxalinones 78, which were cyclized to pyrazolyl-quinazolinones . ... 

The concentration of ascorbate in the human plasma is 25 pM and above. Cells take up ascorbate by a Na -coupled uptake mechanism against a concentration gradient. A marked stereo-selectivity for L-ascorbic acid relative to D-isoascorbic acid in their cellular transport has been shown by Franceschi et al. [12]. The same transport is also important in the intestine. The nutritional supply of ascorbic acid is the only source for this vitamin in humans, primates, and guinea pigs. Other mammals are able to produce ascorbic acid. There exists sufficient evidence for an active role of ascorbate as an antioxidant in vivo. Decreased ascorbic acid will increase lipid peroxidation and decrease vitamin E and is connected with oxidative DNA damage. The supply of ascorbate in some cases will reduce the amount of oxidative damage in diseases that... 

L-ascorbic acid (AA) and its isomer D-erythorbic acid (EA) (also called D-isoascorbic acid) have been used as inhibitors of enzymatic browning in fruit and vegetable products for at least 50 years, (15-17). These compounds prevent quinone accumulation and subsequent pigment formation by reducing the 0-quinones generated from the phenolic substrates of PPO back to O-dihydroxyphenolic compounds (17-18). AA also can act as a PPO inhibitor (19-20). AA and EA are used interchangeably although there are indications that AA is more effective in some systems (21-22). 

The oxidation of ascorbic acid still attracts attention and a mechanism has been proposed for the reaction with photochemically produced H02 radicals. An analogous reaction with hydrogen peroxide affords a means of access to L-threonic acid. Heating D-isoascorbic acid in aqueous pyridine in the presence of boric acid gives the decarboxylation products D-arabinose and D-ribose. Two Russian papers have reported on the oxidation of ascorbic acid with copper(ll) in the presence and absence of oxygen and light. As part of a basic study of the action of oxidase and reductase enzymes, the reduction of Methylene Blue by ascorbic acid has been examined, in the presence of surfactants added to mimic the effects of the protein parts of the enzymes. ... 

Tetroses and Pentoses - 4-0- -Butyldimethylsilyl-2,3-0-isopropylidene-L-threose (1) has been prepared in seven efficient steps from o-xylose. 3,4-0-Isopropylidene-D-eythrulose (4) has been synthesized from the known tetritol derivative 2 by primary protection as the silyl ether 3, followed by Dess-Martin oxidation and desilylation. Compound 2 was derived from D-isoascorbic acid (see Vol. 22, p. 178, refs. 9,10). In a similar reaction sequence, the enantiomer 5 has been obtained from L-ascorbic acid. The dehomologation of several di-0-isopropylidenehexofuranoses e.g., 6- 7) has been carried out in two steps without intermediate purification, by successive treatment with periodic acid in ethyl acetate, followed by sodium borohydride in ethanol. Selective reduction of 3-deoxy-D-g/jcero-pentos-2-ulose (8) to 3-deoxy-D-g/> cero-pent-2-ose (9) has been achieved enzymically with aldose reductase and NADPH." 4-Isopropyl-2-oxazolin-5-one (10) is a masked formaldehyde equivalent that is easily converted to an anion and demasked by mild acid hydrolysis. One of the three examples of its use in the synthesis of monosaccharides is shown in Scheme 1. ... 

A review article has described routes to small, general-purpose chiral synthons from carbohydrates, including the preparation of D-erythronolactone and l-threonolactone from D-isoascorbic and L-ascorbic acids respectively, and the synthesis of lactone 50 and its enantiomer from disaccharides and L-arabinose... 

Chemistry and mode of action. Ascorbic acid has two asymmetric carbon atoms at C5 and C9 positions. As depicted in Figure 9.11, the naturally occurring ascorbic acid is the L-ascorbic acid form, which is a diastereoisomer of D-isoascorbic acid (erythorbic acid). These diastereo-isomers have similar, but not necessarily the same, physicochemical properties. While ascorbic acid is an accepted additive in Australia, the EC and the USA, erythorbic acid and its sodium salt are not permitted in the EC for winemaking. Ascorbic acid occurs naturally in grapes in amounts between 10 and 100 mg/1, but may be rapidly oxidised after crushing and as a result of the associated aeration. 

Pelletier, O., 1969, Turnover rates of D-isoascorbic acid and L-ascorbic acid in guinea pig organs. Can. J. Physiol. Pharmacol. 47 993-997. 

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