Malic acid transformation

The results (mEq/1) assess the consequences. The lactic acid formed corresponds to half of the malic acid transformed. The diminution in fixed acidity corresponds approximately to the difference between the loss in malic acid and the gain in lactic acid. 

The 1,3-dipolar cycloaddition of a five-membered cyclic nitrone derived from malic acid and unsaturated D-t/zreu-hexonolactone led to a single adduct 21, which was transformed into 1-homoaustraline via a sequence of well defined reactions (Fig. 7).16 Synthesis of similar derivatives was presented recently.17... 

Hiemstra and co-workers reported the first example of an iodine-promoted allenyl N-acyliminium ion cyclization for the total synthesis of (+)-gelsedine, the enantiomer of the naturally occurring (-)-gelsedine [72], Compound 341 was prepared from (S)-malic acid. When 341 was dissolved in formic acid with a large excess of Nal and heated at 85 °C for 18 h, 343 was found to be the major product isolated in 42% yield. The latter was then successfully converted to (+)-gelsedine in a multi-step manner. Other routes without the allene moiety failed to provide the desired stereoisomer. The successful one-step transformation of 341 to 343 was key to the success of this synthesis. 

The synthesis of 9-(l,4-dihydroxybut-2-oxy)purines commenced with 2-butene-l,4-diol (1004) and via 1005 to 1006, which upon reaction with 1007 gave 1011 and then, upon hydrolysis, the racemic alkoxyamine 1012. The chiral derivatives commenced with the enantiomers of malic acid (1009) through 1010 to 1008, as shown in the scheme. Treatment of 1012 with 996 and further transformations followed almost the same sequence as before to give 1013. 

The most confusing aspect of the pathway proposed by Ochoa and his group now rests with the NAD requirement. In proceeding from L-malic acid to L-lactic acid, there is no net change in oxidation state. Yet in whole cells or cell-free extracts, the malo-lactic fermentation will not proceed in the absence of NAD. Therefore, by the proposed mechanism, one is unable to demonstrate the appearance of reduced cofactor, and the NAD specificity cannot be explained as a redox requirement. However, in the time since this mechanism was proposed, an NAD dependent enzyme (glyceraldehyde-3-phosphate dehydrogenase) has been described which requires NAD in a non-redox capacity (29), and it is possible that the same is true for the enzyme causing the malic acid-lactic acid transformation. 

It was reported (14) that the adaptive enzyme from Lactobacillus plantarum could decarboxylate oxaloacetic acid as well as malic acid. However, in the same organism, Nathan (30) carried this work further and showed that the oxaloacetate decarboxylase activity is not related at all to the malic acid-lactic acid transformation activity. She based this conclusion on the ability of malic and oxaloacetic acids to induce oxaloacetate decarboxylase activity as well as malic enzyme activity. In her words,... 

Our work (6, 7, 8) has shown that the same protein which causes the malic acid-lactic acid transformation will also cause the production of a small amount of pyruvic acid from malic acid. However, the pyruvic acid produced is not involved with lactic acid production. Apparently, one protein is producing two end products from the same substrate. The malic acid to lactic acid activity is not an oxidoreductase whereas the malic acid to pyruvic acid activity is. Since the pyruvic acid producing activity is only a small per cent (about 0.2%) of the malic acid to lactic acid activity, and since the enzyme should be classified according to the major end product, the enzyme has been given the trivial frame of malo-lactic enzyme (6, 7, 8). Schiitz (28) has speculated that if this enzyme were crystallized, it should be called malate-carboxy-lyase. In either case, use of either the trivial or accepted terms for the malic enzyme is not recommended. 

In the fermentative process, the first step is due to yeasts which transform sugars to alcohol (alcoholic fermentation). This is followed by a second fermentation step (malolactic fermentation), which corresponds to the transformation of L-malic acid to L-lactic acid. 

In this way, it would be possible to convert electrodialytically fumaric acid into ammonium fumarate. This in turn may be enzymatically transformed into ammonium malate, which might finally be ED freed into malic acid with no reagent consumption and by-product formation, and minimum product loss. 

Usually, after alcoholic fermentation, the wine undergoes malolactic fermentation, induced primarily by Oenococcus oeni. Not only can this lactic acid bacterium convert L-malic acid into L-lactic acid but also it is involved in many other transformations fundamental to Amarone quality. 

Of all the metabolic activities that lactic acid bacteria can carry out in wine, the most important, or desirable, in winemaking is the breakdown of malic acid, but only when it is intended for this to be removed completely from the wine by malolactic fermentation. Although the breakdown of malic and citric acids has considerable consequences from a winemaking perspective, it is also evident that lactic acid bacteria metabolise other wine substrates to ensure their multiplication, including sugars, tartaric acid, glycerine and also some amino acids. We will now describe some of the metabolic transformations that have received most attention in the literature, or which have important repercussions in winemaking. 

This is the main reaction of MLR Chemically it consists of a simple decarboxylation of the L-malic acid in wine into L-lactic acid. Biochemically, it is the result of activity of the malolactic enzyme, characteristic of lactic acid bacteria. This transformation has a dual effect. On the one hand, it deacidifies the wine, in other words, it raises the pH, an effect that is greater at higher initial quantities of malic acid. It also gives the wine a smoother taste, replacing the acidic and astringent flavour of the malic acid, by the smoother flavour of the lactic acid. 

This is the main reaction by which MLR causes discrete changes in the organoleptic characteristics of a wine, and is why the second fermentation is especially recom-mendable for most red and many white wines. The duration of this transformation of malic acid depends on the initial amount of this acid present and the total population of bacteria that have multiplied in the wine. However, for the same biomass formed, this process can be slowed down as a consequence of certain inhibitors in the wine, which have not yet been identified. 

The photochemical carboxylation of pyruvic acid by this process is endergonic by about AG° = 11.5 kcal mol and represents a true uphill photosynthetic pathway. The carbon dioxide fixation product can then act as the source substrate for subsequent biocatalyzed transformations. For example, photogenerated malic acid can act as the source substrate for aspartic acid (Figure 35). In this case, malic acid is dehydrated by fumarase (Fum) and the intermediate fumaric acid is aminated in the presence of aspartase (Asp) to give aspartic acid. 

Malolactic fermentation (MLF) is an important process, nowadays also conducted on an industrial scale, aimed at improving organoleptic characteristics and conferring microbiological stability to quality wines (Davis et al., 1985). The main transformation of the wine occurring in this process operated by lactic bacteria, is decarboxylation of L(—)-malic acid with formation of L(+)-lactic acid (Figure 1.5). 

Figure 1.5 Transformation of L(—)-malic acid into L(+)-lactic acid occurring in malolactic fermentation (MLF)...

The Bartlett nonactic acid synthesis, outlined in Scheme 4.33, arose from this group s work in the area of acyclic stereocontrol. From a common intermediate constructed using the carbonate cyclization methodology, Bartlett was able to obtain either antipode of nonactic acid and thus nonactin To this end, dimethyl-(S)-(-)-malic acid 217 was converted by a series of routine chemical transformations to epoxy tosylate 218 in 75% overall yield. Cleavage... 

In a rather lengthy transformation of ( S)-malic acid, acetonide 141 is converted to p-ketophosphonate 142 by reaction with the lithium salt of dimethyl methylphosphonate (Scheme 18) [49]. A Homer—Emmons reaction with cyclohexanecarboxaldehyde produces... 

Reactions at the C-4 carboxyl group of malic acid usually require some sort of prior manipulation at the other end of the molecule to facilitate the desired transformation. For example, tying up both the 1-carboxyl and 2-hydroxyl groups into a dioxolanone ring (173a) makes it possible for the remaining 4-carboxylic acid to be converted easily to an acid chloride (265) under standard conditions. Treatment of 265 with sodium azide followed by a... 

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