Lactose reaction with

Aqueous lactose (40 wt-% in water) and xylose (50 wt-%) solutions were hydrogenated batchwise in a three-phase laboratory reactor (Parr Co.). Reactions with lactose were carried out at 120 °C and 5.0 MPa H2. Xylose hydrogenations were performed at 110 °C and 5.0 MPa. The stirring rate was 1800 rpm in all of the experiments to operate at the kinetically controlled regime. 

Fig. 2. Identification of the reaction products of GalNAc from Haemophilus influenzae Rd by high-performance liquid chromatography. The reactions were carried out as described in Methods. (A) Reaction with lactose as acceptor 1, lactose 2, GalNAcb l,3Lac. (B) Reaction with globotriose as acceptor 3, globotriose 4, globotetraose.

Caseinoglycomacropeptide is split off from x-casein during renneting and thus is present in cheese whey, where it is subject to reaction with lactose. Moreno et al.49 have examined ovine macropeptide and found, by LC-ESIMS, that it was about 60%... 

In Maillard reactions with lactose, the 4-hydroxy group is substituted and hence /1-dicarbonyl formation is blocked, thus preventing the production of 2-acetylpyrroles.30... 

All excipient chemical reactions should be incorporated into the experimental design. For example, drugs that contain primary and secondary amines functionality undergo Maillard reactions with lactose and other reducing carbohydrates such as glucose and maltose under pharmaceutically reasonable conditions.This reaction should be considered during formulation development. Alternative excipients such as mannitol, sucrose, and trahalose, which are not subject to the Maillard reaction, should be used in place of lactose in such cases. 

The MaiUard reaction of lactose and proteins in mUk has long been investigated mainly from a view point of nutritional quaUty of pasteurized and powdered miUc or mUk products (2). AvaUability of an essential amino acid, lysine, is decreased by the reaction with lactose during heating for pasteurization and spray-drying for powdering of milk. Loss of avaUable lysine and production of reaction interm ates are estimated by amino acid analysis of acid hydrolysates of milk samples. 

Figure 20 Post-column detection of mono- and disaccharides with 4-amino-benzoylbenzamide. Column CarboPac PA-1. Gradient 1-10 mm NaOH (0-20 min.), 10-20 mM NaOH (20-35 min). Flow rate 1 ml/min. Detection absorbance at 400 nm after reaction with 4-aminobenzoylhydrazide. (a) Standard mixture of fucose (1), arabinose (2), galactose (3), glucose (4), xylose and N-acetylglucosamine (5 and 6), allose (7), 3-fucosyllactose (8), fructose (9), lactose (10), Man-(3-(l,4)-GlcNac. (b) Normal urine, (c) Urine from a child with (3-mannosidosis. (Reproduced with permission of Academic Press from Peelen, G. O. H., de Jong, J. G. N., and Wever, R. A., Anal. Biochem., 198, 334, 1991.)...

An autocatalytic reaction is one in which the reaction rate is proportional to a product concentration raised to a positive exponent. Some of the first articles in the literature of chemical kinetics deal with reactions of this type. For example, in 1857, Baeyer (12) reported that the reaction of bromine with lactose was autocatalytic. The hydrolyses of several esters also fit into the autocatalytic category, since the acids formed by reaction give rise to hydrogen ions that serve as catalysts for subsequent reaction. Among the most significant autocatalytic reactions are the fermentation reactions that involve the action of a microorganism on an organic feedstock. 

Diffuse reflectance spectroscopy was used to screen the possible interactions between a large number of adjuvants and several dyes [23]. It was concluded that supposedly inert excipients (such as starch or lactose) were capable of undergoing significant reactions with the dyes investigated (Red No. 3, Blue No. 1, and Yellow No. 5). For adjuvants containing metal ions (zinc oxide, or calcium, magnesium, and aluminum hydroxides), the degree of interaction could be considerable. It was concluded from these studies that dye-excipient interactions could also be responsible for the lack of color stability in certain tablet formulations. 

The reaction of a primary amine with lactose is accompanied by a browning of the solids, and the path of such reactions is easily following by means of diffuse reflectance spectroscopy. For instance, the reaction of isonicotinic acid hydrazide (Isoniazid) with lactose could be followed through changes in the reflectance spectrum [31]. As may be seen in Fig. 4, a steady decrease in reflectance was noted as the sample was heated for increasing amounts of time. The spectral data were used to deduce the rate constants for the browning reaction at various heating temperatures, and these rates could be correlated with those... 

Fig. 4 Reflectance spectra of the reaction products formed when isonicotinic acid hydrazide (Isoniazid) reacts with lactose. Reflectance spectra are shown for (A) the initially prepared material, and for samples illuminated for (B) 4 hours, (C) 10 hours, (D) 21 hours, and (E) 44 hours. (Data adapted from Ref. 31.)...

The reaction of neomycin with many compounds has been described in Section 3, hence numerous reports of neomycin incompatibility may be expected. Dale and Rundman have extensively reviewed the compatibility of neomycin with substances that may be encountered by the formulation pharmacist. Kudalker et al 03 have described the incompatibility of the antibiotic with rancid oils, and the incompatibility with bentonite, a montomorill-onite clay, has been reported by Danti and Guth306. The incompatibility with lactose, causing a discoloration of the mixture has been studied by Hammouda and Salakawy- 0 . The amount of browning produced was shown to be dependant on the initial pH of the solution. The rate of discoloration of the lactose/neomycin powder was directly related to the temperature of storage and the relative humidity of the atmosphere. Discoloration was overcome by addition of sodium bisulphite. 

To achieve these lactose-purpurinimide conjugates 89-93, in the macrocycle positions 3, 8, 12, the purpurin-18-methyl ester 81 had to undergo several chemical transformations to obtain the desired hydroxymethyl group.68 Such alcohol derivatives were reacted with lactose octaacetate in the presence of boron trifluoride diethyl etherate to induce the acetylated lactose-purpurinimide derivative which, after deacetylation reaction conditions, yielded the desired compounds in excellent amounts (Scheme 12). 

The derivative 90 was obtained by condensation of the purpurin-18-A-hexylimide-17-propionic acid with aminolactose heptaacetate in the presence of benzotriazol-l-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) followed by the deacetylation procedure. The lactose-photosensitiser conjugate linked by an ethylene moiety was also prepared by following a similar approach. The purpurin-18-methyl ester 81 was converted into /V-(3-iodobenzyl)/ /evo-purpurin-18-7V-hexylimide-17-propionic ester by hydrogenation over Pd/C followed by reaction with 3-iodo-benzylamine. Afterwards, the propargyllactose heptaacetate reacted with A-(3-iodobenzyl)rMeio-purpurin-18-A-hexylimide-l 7-propionic ester in the presence of tris(dibenzylidieneacetone)dipalladium(0) (Pd2-dba3) which, after deacetylation conditions, afforded the derivative 89 (Fig. 9).68... 

Orotic acid in the diet (usually at a concentration of 1 per cent) can induce a deficiency of adenine and pyridine nucleotides in rat liver (but not in mouse or chick liver). The consequence is to inhibit secretion of lipoprotein into the blood, followed by the depression of plasma lipids, then in the accumulation of triglycerides and cholesterol in the liver (fatty liver) [141 — 161], This effect is not prevented by folic acid, vitamin B12, choline, methionine or inositol [141, 144], but can be prevented or rapidly reversed by the addition of a small amount of adenine to the diets [146, 147, 149, 152, 162]. The action of orotic acid can also be inhibited by calcium lactate in combination with lactose [163]. It was originally believed that the adenine deficiency produced by orotic acid was caused by an inhibition of the reaction of PRPP with glutamine in the de novo purine synthesis, since large amounts of PRPP are utilized for the conversion of orotic acid to uridine-5 -phosphate. However, incorporation studies of glycine-1- C in livers of orotic acid-fed rats revealed that the inhibition is caused rather by a depletion of the PRPP available for reaction with glutamine than by an effect on the condensation itself [160]. 

L. Hough, A. C. Richardson, and L. A. W. Thelwall, Reaction of lactose with 2,2-dimethoxypropane. A tetra-acetal of novel structure, Carbohydr. Res., 75 (1979) C11-C12. 

To further exploit the potential usefiilness of this new family of clusters, monoadduct 54 was saponified into 55 (0.05 M NaOH, quant) and condensed to L-lysine methyl ester using 2-ethoxy-l-ethoxycarbonyl-l,2-dihydroquinoline (EEDQ) to give extended dimer 56 in 50 % yield together with monoadduct in 15 % yield [75]. Additionally, tert-butyl thioethers 52 could be transformed into thiols by a two step process involving 2-nitrobenzenesulfenyl chloride (2-N02-PhSCl, HOAc, r.t, 3h, 84%) followed by disulfide reduction with 2-mercaptoethanol (60%). Curiously, attempts to directly obtain these thiolated telomers by reaction with thioacetic acid f ed. These telomers were slightly better ligands then lactose in inhibition of binding of peanut lectin to a polymeric lactoside [76]. 

Lactosyl urea. Urea can serve as a cheap source of nitrogen for cattle but its use is limited because NH3 is released too quickly, leading to toxic levels of NH3 in the blood. Reaction of urea with lactose yields lactosyl urea (Figure 2.26), from which NH3 is released more slowly. 

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