Synthesis of Orotic Acid from Aspartic Acid

Nyc, Joseph F.; Mitchell, Herschel K.

doi:10.1021/ja01198a042

Cited by 147 publications

(43 citation statements)

References 4 publications

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“…Carbamylphosphate (CAP) was synthesized and analyzed as described by Jones, Spector and Lipmann (2). I-Carbamylaspartate-C14 (CAA-C") was prepared from I-aspartate and cyanate-C14 (3) and measured by the Koritz and Cohen procedure (4). Cyanate-C14 was synthesized by the fusion of potassium carbonate and urea-C14 (5).…”

Section: Methodsmentioning

confidence: 99%

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Pyrimidine Metabolism in Man. I. The Biosynthesis of Orotic Acid*†

Smith¹,

Baker²

1959

J. Clin. Invest.

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Section: Methodsmentioning

confidence: 99%

“…2 Disodium ethylenediaminetetraacetate in saline. 3 Lot number HH-1, R. K. Laros Co., Bethlehem, Pa. 798 so that they constituted approximately 80 to 90 per cent of the total leukocytes. The number of contaminating erythrocytes was usually three to six times greater than the leukocytes.…”

Section: Methodsmentioning

confidence: 99%

Pyrimidine Metabolism in Man. I. The Biosynthesis of Orotic Acid*†

Smith¹,

Baker²

1959

J. Clin. Invest.

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“…The reaction was follo~xlecl spectrophotometi-ically in a1l;alil~e solution and it xvas f o u i~I that orotic acid is formecl previous to acidification. The hyclantoic acicl was not isolated, though in other uilsaturated hyclantoins eviclerzce of the open-chain compound has been obtaiiied (14). T h a t an open-chain-ring tautomerisin exists in the hydaittoin conversion to orotic acid \\as clearly demonstrated by Langley (15), who was able to show that a C1' carbolt atom in position four in the hydantoin ring is present as a carboxyl in the orotic acid; this Ivas confirmecl by the quantitative recovery of the raclioactivity in the COs follon~ing clecarboxylation (the remaining ~lracil beiitg inactive).…”

mentioning

confidence: 97%

“…A11 these facts prompted us to reinvestigate the mechanism of the formation of orotic acid aitcl xve chose a t first the reaction of eth>,l osaloacetate and urea (I11 -+ I ) , as described by 1Iiiller (13) ancl discussed by S > -c aitd 1Iitchell (14). The latter authors postulated a mechanism which iltvolves opening of the hyclantoin ring betweeit positions three ctlld four to give tlte hyclantoic acid which closes again to give the pyrimicline.…”

mentioning

confidence: 99%

Orotic Acid and Its Analogues: Part Ii. On the Alkaline Rearrangement of 5-Carboxymethylidenehydantoin

Deghenghi¹,

Daneault²

1960

Can. J. Chem.

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The in vitro conversion of 5-carboxy~~lethylidenehyda~itoin to orotic acid is not likely to occur in \.ivo since the two substances have antagonistic elfects (2). A sulphur analogue of the above hydantoin has been prepared and shown not to undergo alkaline rearrangelnent to the corresponding metathiazine structure. The mechanism of orotic acid formation is discussed.Since its discover) in 1905 by Biscaro and Belloni (3), orotic acid (11) has aroused an ellornlous interest among biochemists (see in particular (4) and (5)) for its importance as a pyrimidine precursor of 11ucleic acids. A large amount of synthetic work has been done on orotic acid itself (6) and on its analogues ('i), but comparatively little attention has been given to the mechanisms of its formation, from a p~lrely chemical point of viexv.At first orotic acid \\.as believed to be a seven-mentbered ring contpound (3), but it was soon shox\.11 to be uracil-6-carboxylic acid (8, 9). Its synthesis froin ethyl oxaloacetate and urea xvas el-roneousl>. believed to give directly ethyl orotate (10) ; later the ester was proved to be in fact 5-carbethoxymethylidenehydmtoin (11). X similar error was made by Biltz and Iiramer (12), xvho st~ldied the alkaline decomposition of a diazoacetate clerivative of alloxait to give again the hyclantoin and not the six-membered ring ester.A11 these facts prompted us to reinvestigate the mechanism of the formation of orotic acid aitcl xve chose a t first the reaction of eth>,l osaloacetate and urea (I11 -+ I ) , as described by 1Iiiller (13) ancl discussed by S > -c aitd 1Iitchell (14). The latter authors postulated a mechanism which iltvolves opening of the hyclantoin ring betweeit positions three ctlld four to give tlte hyclantoic acid which closes again to give the pyrimicline. The reaction was follo~xlecl spectrophotometi-ically in a1l;alil~e solution and it xvas f o u i~I that orotic acid is formecl previous to acidification. The hyclantoic acicl was not isolated, though in other uilsaturated hyclantoins eviclerzce of the open-chain compound has been obtaiiied (14). T h a t an open-chain-ring tautomerisin exists in the hydaittoin conversion to orotic acid \\as clearly demonstrated by Langley (15), who was able to show that a C1' carbolt atom in position four in the hydantoin ring is present as a carboxyl in the orotic acid; this Ivas confirmecl by the quantitative recovery of the raclioactivity in the COs follon~ing clecarboxylation (the remaining ~lracil beiitg inactive). We were iitterested Can.

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“…or uracil and one of its precursors., orotic acid, are involved in /8-alanine formation in these seed plants. Evidence (30). Uracil-4, 5-C'4 was synthesized from malic-2, 3-C'4 aci(l and(l urea followiing the procedure of Davidson andl Baudisch (14).…”

mentioning

confidence: 99%