Laevulinic acid

Bromomethyl-5-methylthiophene gives normal displacement products with amines but it is isomerized on attempted reaction with copper(I) cyanide (Scheme 59) 48MI30200. Whereas 2-hydroxymethylthiophene reacts normally with hydrogen halides to give 2-halomethylthiophenes, reaction of 2-hydroxymethylfuran (2-furfuryl alcohol) with hydrochloric acid results in formation of laevulinic acid (151). 2-Furfuryl alcohol derivatives are... 

Laevulinic acid (52) appears in the list of readily available 1,4-difunctionklised compounds. It is in fact... 

The disconnection (53a) needed to find the skeleton of laevulinic acid corresponds to the Wittig reaction and the rest is straightforward. 

Alkyl methyl ketones undergo nitrosation at the reactive methylene group when treated with nitrous acid or an alkyl nitrite [Method (fi)]. The presence of hydrogen on the a-carbon permits tautomeric rearrangement to the oxime of a 1,2-dicarbonyl compound. Acidic hydrolysis of the oxime, which is best carried out in the presence of a hydroxylamine acceptor such as laevulinic acid,143 affords a further useful route to the 1,2-dicarbonyl system. 

Red 2 exposed to different sugar degradation products at 100 °C gave the following %A values (min) glyceraldehyde, 20 glycolaldehyde, 30 triose reductone, 40, dihydroxyacetone, 50 2-oxopropanoic acid, 60 3-hydroxy-2-butanone, 90 butane-dione, 300 HMF, 450 2-oxopropanal, 1200 acetaldehyde, acrolein, and laevulinic acid, no reaction. 

Laevulinic Acid.—This acid is much better adapted for the synthesis of the corresponding diketone -than is pyroracemic acid. Hofer,3 on electrolyzing the potassium salt of the acid obtained about 50% of the theoretically expected quantity of 2,7-octandion ... 

Propionic acid, crotonic acid, benzoic acid, succinic acid, maleic and fumaric acid, phthalic acid, camphoric acid, glycollic acid, lactic acid, malic acid, tartaric acid, the oxybenzoic acids, pyroracemic acid, laevulinic acid, dehydracetic acid, and aceto-acetic acid (or its esters). 

Figure 1 An example of the way metallo-enzymes are under controlled formation through both controlled uptake (rejection) of a metal ion and controlled synthesis of all the proteins connected to its metabolism and functions. The example is that of iron. Iron is taken up via a molecular carrier by bacteria but by a carrier protein, transferrin, in higher organisms. Pumps transfer either free iron or transferrin into the cell where Fe + ions are reduced to Fe + ions. The Fe + ions form heme, aided by cobalamin (cobalt 2 controls) and a zinc enzyme for a-laevulinic acid (ALA) synthesis. Heme or free iron then goes into several metallo-enzymes. Free Fe + also forms a metallo-protein transcription factor, which sees to it that synthesis of all iron carriers, storage systems, metallo-proteins, and metallo-enzymes are in fixed amounts (homeostasis). There are also iron metallo-enzymes for protection including Fe SOD (superoxide dismutase). Adenosine triphosphate (ATP) and H+ gradients supply energy for all processes. See References 1 -3.

Levulinic Acid. 4-Oxopenlanoic acid laevulinic acid -acetyl propionic acid. CjHtO, mol wt 116.11. C 51.72%, H 6.94%, O 41.34%. CHjCOCHjCHjCOOH. Laboratory procedure from starch Or cane sugar by boiling with 1ICI. McKenzie, Org. Syn. coll. vol. 1, 335 (1941). Produced commercially from low grade cellulose. By-product of furfural manuf. Extensive review Leonard, Ind. Eng. Chem. 48, 1331 (1956). 

Araki, S. (1980). Effects of urinary volume on urinary concentrations of lead, delta-amino-laevulinic acid, coproporphyrin, creatinine, and total solutes. Br. J. Ind. Med., 37, 50. 

E.V. Ross, R. Romero, N. Kollias, C. Crum, R.R. Anderson (1997). Selectivity of protoporphyrin IX fluorescence for condylomata after topical application of 5-amino-laevulinic acid implications for photodynamic treatment. Br. J. Dermatol, 137, 736-42. 

P. Collins, D.J. Robinson, M.R. Stringer, G.I. Stables, R.A. Sheehan-Dare (1997). The variable response of plaque psoriasis after a single treatment with topical 5-amino-laevulinic acid photodynamic therapy. Br. J. Dermatol., 137, 743-749. 

P.G. Calzavara-Pinton (1995). Repetitive photodynamic therapy with topical 5-amino-laevulinic acid as an appropriate approach to the routine treatment of superficial nonmelanoma skin tumors. J. Photochem. Photobiol. B Biol., 29, 53-57. 

The benzoylated hydrazone resin (150 mg, 0.11 mmol) was suspended in 6 mL dichloroethane/trifluoroacetic acid (1/1). Then 10 eq. laevulinic acid was added, and the mixture was heated for 15 min to 2 h at 70°C. After cooling, the mixture was quenched with methanol, and the resin was filtered and washed with 5 mL dichloromethane, methanol, ethyl acetate, and methanol. The filtrate was evaporated to dryness, and the crude product was purified by preparative HPLC. Finally, [l-(4-bromobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid was obtained as white solid, in a yield of 57% with a purity of > 99% (HPLC), m.p. 15rC. 

Laevosan. See Fructose Laevulic acid Laevulinic acid. See Levulinic acid... 

Elegant work based on double C-labelling and NMR spectroscopy has demonstrated the process by which natural type III porphyrins are biosynthesized [228,229]. [2,ll- C2]Porphobilinogen (29) was prepared enzymatically from amino [5- C]laevulinic acid (30), the preparation of which had previously... 

Extensive work has been reported on C-NMR studies of C-enriched samples of vitamin B12 [231]. The enrichment was carried out by feeding 5-amino [2- C]laevulinic acid, 5-amino [5- C]laevulinic acid, [8- C]porphobilinogen, L-methionine ( C-methyl), and C-labelled uroporphyrinogen. The study, which provided evidence of the location of the labelled centres in the vitamin, showed the intact incorporation of porphobilinogen and uroporphyrinogen III into vitamin B12. 

Recently this type of study has been undertaken in order to quantitate ineffective erythropoiesis in normal subjects [393] and in patients with a variety of haematological disorders [387]. In these investigations the incorporation of [ N]glycine into early labelled bilirubin and haemoglobin haem was measured. [ Cj Bilirubin clearance was used to estimate total bilirubin production rate [394], and hepatic haem turnover was calculated from the incorporation of a-amino [ N]laevulinic acid into early labelled bilirubin. The relative contribution of ineffective erythropoiesis in the production of anaemia found in these... 

Haemopoietic lead inhibits haem production, giving rise to the excretion of D-amino laevulinic acid and coproporphyrin III. Features of anaemia include pallor, a reduction of haemoglobin with the occurrence of punctate basophilia in erythrocytes and an increase in reticulocyte count. 

Two enzyme systems have shown themselves to be extremely sensitive to lead at low levels. The first of these is D-amino laevulinic acid dehydratase (d-ALAD), the initial and rate limiting step in the porphyrin synthetic pathway. In both experimental (Barlow et al., 1977) and clinical studies (Piomelli et al., 1980) this enzyme is potently inhibited by lead. In a review of dose-dependent low level lead effects, Zielhuis (1975) calculated a no effect level for this enzyme at about 10/tg Pb/lOOml blood in man. Other enzymes in the porphyrin synthetic pathway are also affected by lead, e.g. ferrochelatase, the enzyme responsible for the insertion of haem into the porphyrin precursor protoporphyrin IX (Moore, 1975), but this is probably due to D-ALAD-related interactions. Silbergeld and Lamon (1980) have speculated that the neurotoxic effects of lead may be due in part to a competitive interaction involving amino laevulinic acid at neuronal receptors, as there may be similarities between features of lead toxicity and some of the porphyrinopathic diseases (Moore et al., 1980). 

The reported neurochemical effects of lead are, as has been seen, enormous. They can be broadly summarized by neurotransmitter system cholinergic impairment at relatively high levels (usually in the presence of non-specific effects), dopaminergic effects at low levels, and impairment at higher levels (in the presence of obvious non-specific effects), GABAergic effects at levels where a complication from the interaction with D-amino laevulinic acid also occurs. There is also a mixed bag of effects on enkephalin, adenyl cyclase, 5-hydroxytrypamine and other putative aminergic neurotransmitters. 

Lead interferes with the normal formation of haemoglobin, causing anaemia, but the diagnosis of excessive absorption should be made before anaemia appears. The same interfering mechanism causes abnormal products to appear in the urine, e.g. amino laevulinic acid (ALA) and coproporphyrin. These products are useful indicators of excessive lead absorption or poisoning. 

A useful indicator of excessive lead effect is the presence of free erythrocytic porphyrin (FEP). It can be measured from a small quantity of blood obtained by finger-prick. For confirmatory evidence of excessive lead absorption or poisoning, urine estimation of coproporphyrin and amino laevulinic acid are helpful. Inorganic lead is best monitored by blood sampling and organic lead by urine sampling. 

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