Orotate

Orotic acid (2,6-dioxo-l,2,3,6-tetrahydropyrimidine-4-carboxylic acid)... 

The aminolysis of esters of pyrimidine occurs normally to yield amides. The reagent is commonly alcoholic ammonia or alcoholic amine, usually at room temperature for 20-24 hours, but occasionally under refiux aqueous amine or even undiluted amine are used sometimes. The process is exemplified in the conversion of methyl pyrimidine-5-carboxylate (193 R = Me) or its 4-isomer by methanolic ammonia at 25 °C into the amide (196) or pyrimidine-4-carboxamide, respectively (60MI21300), and in the butylaminolysis of butyl ttracil-6-carboxylate (butyl orotate) by ethanolic butylamine to give A-butyluracil-5-carboxamide (187) (60JOC1950). Hydrazides are made similarly from esters with ethanolic hydrazine hydrate. 

Orotic acid (971) has a chequered history. It was isolated in 1905 from the whey of cows milk in Italy and it was subsequently synthesized in the United States in 1907. However, the workers involved were discouraged by some difference in melting points and no direct comparison of specimens was ever made. To make matters worse, the same laboratories prepared the isomeric 5-hydroxy-2-oxo-l,2-dihydropyrimidine-4-carboxylic acid and announced it as orotic acid, again without any direct comparison. Only in 1930 did a German worker actually compare directly natural and the original synthetic orotic acid, thereby showing them to be identical (30CB1000). 

There are at least eight syntheses of orotic acid in the literature. The most practical in the laboratory is that involving the condensation of diethyl oxalacetate (972) with S-methylthiourea to give 2-methylthio-6-oxo-l,6-dihydropyrimidine-4-carboxylic acid (973) which undergoes either direct acidic hydrolysis or a less smelly oxidative hydrolysis, via the unisolated sulfone (974), to afford orotic acid (971) (B-68MI21303). 

Orotic acid undergoes 5-nitration, 5-bromination in hydrobromic acid with peroxide, 5,5-dibromination following decarboxylation in bromine water, esterification, methylation (rather complicated), conversion into its acid chloride (containing some anhydride) by treatment with thionyl chloride, and conversion into 2,6-dichloropyrimidine-4-carboxylic acid by phosphoryl chloride (62HC(16)422). 

Therapeutic Function Treatment of liver diseases Chemical Name 5-aminoimidazole-4-carboxamide orotate Common Name AICA orotate Structural Formula a... 

Chitosan for oral administration to humans is generally recognized as safe. In vitro, chitosan has been reported to bind bile acids The role of the accompanying anion is important for instance chitosan orotate salt has enhanced capacity for bile acids [11,264-267]. 

F Lysortine (Theraplix as 1 lysine orotate) wfm Oroturic (Gremy-Longuet) J wfm... 

C2H4N2 540-61-4) see Estazolam Orotic acid aminoacetonitrile monohydrochloride (C2H5CIN2 6077-/4-9) see Octopamine... 

C,Hi)BrO 79465-06-8) see Indinavir sulfate 5-bromodihydroorotic acid (CjH5BrN204 58668-21-6) see Orotic acid 9-bromo-lip,21-dihydroxy 16a-methylpregna-l,4-diene-3,20-dione 21-acetate... 

C4H4O2 674-82-8) see Aranidipine Bamidipine Benidipine Butoctamide Efonidipine hydrochloride ethanol Epirizole Ketazolam Leflunomide Lercanidipine hydrochloride Manidipine Nimodipine Orotic acid diloxanide... 

C2H2O3 298-12-4) see Allantoin Ethyl biscoumacetate Lamivudine Orotic acid gold iodide (Aul)... 

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