Hydroxyl group enolic

The chemical methods can be subdivided into two interrelated groups (a) those which depend on the reactivity of a particular structural feature, e.g., a carbon-carbon double bond or an enolic hydroxyl group, that is present in only one of the tautomeric forms and (b) those which involve relating the structures of reaction products to the structures of the starting materials. 

V. Analogs of l-Ascorbic Acid Containing One Enolic Hydroxyl Group. 101... 

High antiscorbutic power is also reported to be shown by a derivative of L-ascorbic acid in which the enolic hydroxyl group at C2 is replaced by an amino group. 3,4-Isopropylidene-L-threonic acid (LX), prepared from 5,6-isopropylidene-L-ascorbic acid, is converted into the 2-acetyl-3,4-isopropylidene-L-threonyl chloride (LXI) and this is then allowed to react with the sodium derivative of ethyl malonate. 

There is little doubt therefore that all the true analogs of L-ascorbic acid discussed above contain the unsaturated five atom ring system to which are attached two enolic hydroxyl groups on the carbon atoms of the double bond. 

L-dihydroxy-succinic acid (L(dexiro)-tartaric acid, CXIII). This result establishes the position of the double bond between C4 and C5 and demonstrates that C4 carries only one hydrogen atom while C5 has attached to it the enolic hydroxyl group. Treatment of the enol CXI with ethereal diazomethane gives 5-methyl-A4-D-glucosaccharo-3,6-lactone methyl ester (CXIY) which upon further methylation with silver oxide and methyl iodide yields 2,5-dimethyl-A4-D-glucosaccharo-3,6-lactone methyl ester (CXV). When the latter is subjected to ozonolysis there is formed oxalic acid and 3-methyl-L-threuronic acid (CXVI). Oxidation of this aldehydic acid (CXYI) with bromine gives rise to a monomethyl derivative (CXVII) of L-ilireo-dihydroxy-succinic acid. 

Vitamin C, also known as L-ascorbic acid, clearly appears to be of carbohydrate nature. Its most obvious functional group is the lactone ring system, and, although termed ascorbic acid, it is certainly not a carboxylic acid. Nevertheless, it shows acidic properties, since it is an enol, in fact an enediol. It is easy to predict which enol hydroxyl group is going to ionize more readily. It must be the one P to the carbonyl, ionization of which produces a conjugate base that is nicely resonance stabilized (see Section 4.3.5). Indeed, note that these resonance forms correspond to those of an enolate anion derived from a 1,3-dicarbonyl compound (see Section 10.1). Ionization of the a-hydroxyl provides less favourable resonance, and the remaining hydroxyls are typical non-acidic alcohols (see Section 4.3.3). Thus, the of vitamin C is 4.0, and is comparable to that of a carboxylic acid. 

Evolution of water is noticeable from ca. 130° upward this is a result of lactone formation between the enolic hydroxyl group of the /3-dicarbonyl unit and the aromatic carboxylic acid group. 

In oxalates and a-keto esters, as in a-diketones, there appears to be little or no interaction between the two carbonyl groups so that normal absorption occurs in the region of 1755-1740 cm-1. In the spectra of /3-keto esters, however, where enolization can occur, a band is observed near 1650 cm 1 that results from hydrogen bonding between the ester C=0 and the enolic hydroxyl group. 

Inspection of the molecular structures for n-glucosone (LIII) and kojic acid (LIV) shows that the carbon atom which contained the ketonic carbonyl group in the n-glucosone molecule contains the enolic hydroxyl group in kojic acid. 

The enolic hydroxyl group on the coumarin moiety behaves as a rather strong acid (pKa 4.3) and is the group by which the commercially available sodium and calcium salts arc formed. The phenolic -OH group on the benzamido moiety also behaves as an acid but is weaker than the former, with a pKa of 9.1. Disodium salts of novobiocin have been prepared. The. sodium salt is stable in dry air but loses activity in the presence of moisture. The calcium salt is quite water insoluble and is used to make aqueous oral suspensions. Because of its acidic characteristics, novobiocin combines to form salt complexes with basic antibiotics. Some of the.se saits have been investigated for their combined antibiotic effect, but none has been placed on the market, as they offer no advantage. 

Because the enol hydroxyl group is often quite weak and broadened, it is often difficult to locate its resonance in the offset range beiow 10 ppm. 

Warfarin is a stable, colourless, odourless and essentially tasteless compound. Owing to its enolic hydroxyl group in position 4, it has an acidic character and forms a water-soluble salt with sodium hydroxide or sodium carbonate. Its acute oral LDjo ranges from 58 to 323 mg/kg, depending on the rat species (Oettingen et al.. 1975). 

They resemble hyperforin in their chemical structure, having in addition a 2,2-dimcthyl-2//-pyran ring, most probably derived by the cyclization of a 3-methylbut-2-enyl side chain with an enolic hydroxyl group. Only a few reports describe a similar natural tricyclic system [59-60]. 

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