Malate salt

The following question would be entirely justified. Why the L-malate salt and not the D-malate or the DL-malate The answer is simple there was a bottle of L-malic acid in the lab at the time of initiating the salt-screening exercise, and we did not have the D- or DL- forms. The development of the L-malate salt proceeded so rapidly that project timelines would have been delayed had a switch to the D- or DL- form been attempted. 

Addition of L-malic acid to the reaction mixture containing free base 2 followed by concentration by vacuum distillation led to precipitation of sunitinib malate (1), which was isolated by filtration. The filtration of the L-malate salt took only about 30 min on a 50-kg scale (compared to 8 h for 13 kg of the free base), thereby vindicating the choice of the L-malate salt as the API. 

H02C(CH2)2C02H. Colourless prisms m.p. 182 C, b.p. 235°C. Occurs in amber, algae, lichens, sugar cane, beets and other plants, and is formed during the fermentation of sugar, tartrates, malates and other substances by a variety of yeasts, moulds and bacteria. Manufactured by the catalytic reduction of maleic acid or by heating 1,2-dicyanoethane with acids or alkalis. Forms an anhydride when heated at 235°C. Forms both acid and neutral salts and esters. Used in the manufacture of succinic anhydride and of polyesters with polyols. 

Ca.ndy. Its low melting point and sugar inversion properties make malic acid a desirable acidulant, especially in hard candy products (44,45). Due to their insolubiUty, hard water salts can cause clouding of the finished product. However, because of the higher solubiUty of calcium malate [17482-42-7] relative to alternative acidulants, clarity of the finished product is enhanced. Additionally, in sugar confectionery products where acidulation may exceed 2.0%, malic acid can provide economic benefits. 

OC-Hydroxycarboxylic Acid Complexes. Water-soluble titanium lactate complexes can be prepared by reactions of an aqueous solution of a titanium salt, such as TiCl, titanyl sulfate, or titanyl nitrate, with calcium, strontium, or barium lactate. The insoluble metal sulfate is filtered off and the filtrate neutralized using an alkaline metal hydroxide or carbonate, ammonium hydroxide, amine, or alkanolamine (78,79). Similar solutions of titanium lactate, malate, tartrate, and citrate can be produced by hydrolyzation of titanium salts, such as TiCl, in strongly (>pH 10) alkaline water isolation of the... 

Potassium hydrogen malate [4675-64-3] M 172.2. A saturated aqueous solution at 60° was decolorised with activated charcoal, and filtered. The filtrate was cooled in water-ice bath and the salt was ppted by addition of EtOH. After being crystallised five times from ethanol-water mixtures, it was dried overnight at 130° in zir [Edenand Bales J Res Nat Bur Stand 62 161 1959],... 

The purity of (/-a-phenylethylamine-/-malate is not readily determined by its melting point or specific rotation, but rather by its massive crystalline form and solubility. The acid and neutral /-base-/-acid salts are much more soluble, and usually do not crystallize at all. 

The procedure for preparing 6-hydroxynicotinic acid is also based on a method described by von Pechmann. 6-Hydroxynico-tinic acid has also been prepared by decarboxylation of 6-hy-droxy-2,3-pyridinedicarboxylic acid by heating 6-hydra-zinonicotinic acid or its hydrazide with hydrochloric acid by the action of carbon dioxide on the sodium salt of a-pyridone at 180-200 and 20 atmospheres by heating the nitrile of 6-chlo-ronicotinic acid with alcoholic sodium hydroxide or hydrochloric acid from 6-aminonicotinic acid and by the prolonged action of concentrated ammonium hydroxide on methyl cou-malate. ... 

In the resolution of 1-phenylethylamine using (-)-malic acid, the compound obtained by recrystallization of the mixture of diastereomeric salts is (/ )-1-phenylethylammonium (S)-malate. The other component of the mixture is more soluble and remains in solution. What is the configuration of the more soluble salt ... 

The strongest known producer of j8-poly(L-malic acid) has been identified as Aureobasidium sp. providing 61 g of polymer from 1 liter of culture medium [5,6]. 8-Poly(L-malate, Ca -salt) of the culture broth was first separated from accompanying bulk pullulan by methanol precipitation. The water-redisolved precipitate was converted to the polymer acid by passage over Amberlite IR-120B (H -form). Thus, the best to-day producers of... 

The purification of j8-poly(L-malic acid) from A o-basiae has been reported involving methanol precipitation of the polymer in the form of the Ca salt [5]. This is possible because a high concentration of CaCOs is present in the growth medium. Unfortunately, the polymer acid is not soluble in aceton thus missing an additional purification step. In our hands, purification of jS-poly(L-malate) from several Aureobasidiae strains was unsatisfactory because of low yields and resisting impurities. 

Remove traces of ethanol and dissolve precipitate in a minimum (10 ml) of distilled water. Molecular sieving on a Sephadex G25 fine column (1300 ml, 0 5 cm). Assay fraction for /3-poly(L-malate) and chloride ions. Use only salt-free fractions. 

Obtain pure /3-poly(L-malate) potassium salt by lyophylization. Store in the freezer. 

Poly(L-malate) decomposes spontaneously to L-ma-late by ester hydrolysis [2,4,5]. Hydrolytic degradation of the polymer sodium salt at pH 7.0 and 37°C results in a random cleavage of the polymer, the molecular mass decreasing by 50% after a period of 10 h [2]. The rate of hydrolysis is accelerated in acidic and alkaline solutions. This was first noted by changes in the activity of the polymer to inhibit DNA polymerase a of P. polycephalum [4]. The explanation of this phenomenon was that the degradation was slowest between pH 5-9 (Fig. 2) as would be expected if it were acid/base-catalyzed. In choosing a buffer, one should be aware of specific buffer catalysis. We found that the polymer was more stable in phosphate buffer than in Tris/HCl-buffer. 

Figure 2 Stability of /3-poly(L-malate) measured by its activity to inhibit purified DNA polymerase a of P. polyceph-alum. The relative degree of inhibition is shown (100 rel. units refer to complete inhibition). The DNA polymerase assay was carried out in the presence of 5 /tg/ml /S-poly(L-malate) as described [4]. The polymer was preincubated for 7 days at 4°C in the following buffer solutions (50 mM) KCl/HCl (—A—). Citrate (—V—). 2-(A/-Morpholino)-ethanesulfonic acid, sodium salt (—O—). Sodium phosphate (— —). N-(2-Hydroxyethyl)piperazine-N -(2-ethanesul-fonic acid), sodium salt (— — ). N,N-b s (2-Hydroxyethyl)-glycine, sodium salt (—T—). Tris/HCl (— —). 3-(Cyclo-hexylamino)-l-propanesulfonic acid, sodium salt (— —).

Boron zirconimn chelates from ammonium hydroxide water-soluble amines sodium or potassimn zirconium and organic acid salts such as lactates, citrates, tartrates, glycolates, malates, gluconates, glycerates, and mandelates with polyols such as glycerol, erythritol, arabitol, xylitol, sorbitol, dulcitol, mannitol, inositol, monosaccharides, and disaccharides [463,464,1592,1593]... 

The change with the concentration cannot be due to the reversible formation and decomposition of a lactone of the ordinary type because we get the effect with ethyl malate as well as with malic add. The change cannot be due to a reversible conversion of laevo-malic acid into dextro-malic add, because then a solution of equivalent amounts of dextro- and laevo-malic acids would become optically active on addition of salts, adds and bases. Hydrochloric add or sodium hydroxide imparts no activity to a solution of d/-malic add. The changes on adding electrolytes to a solution of dextro-malic add are equal and opposite in sign to the changes in laevo-malic acid under the same conditions. 

The neutral 6 2 3 molar ratio CCM salt is comprised of 23.7% elemental Ca on a dry weight basis. Various states of hydration of the CCM powder will of course yield slightly lower Ca contents and the preparation of an octa-hydrate form of CCM powder (6 2 3 molar ratio) that comprises 20.73% Ca by weight has been described previously (Fox et ah, 1993b). CCM compositions with a higher proportion of citrate and/or malate moieties (e.g., 4 2 3 molar ratio) will contain a proportionally lower Ca content. Table 6.3 lists the Ca content of various Ca salts. 

Based on the tabulated values, it can be seen that CCM, with its solubility in water slightly over 1% by weight at 25 °C, is approximately 500 and >150-700 times more soluble than tricalcium phosphate and CaCOa, respectively. As individual Ca salts, Ca malate and Ca citrate have relatively low solubility in water compared to CCM (by approximately three- and tenfold, respectively). Since there are multiple chemical formulas for CCM, solubility profiles will also vary. CCM compositions with less Ca relative to the amount of accompanying organic acids are... 

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