β-Ureido acids and dihydrouracils. Part 15. Effect of allylic strain on ring opening of 1,6-disubstituted dihydrouracils

Koedjikov, Asen H.; Blagoeva, Iva B.; Pojarlieff, Ivan G.; Stankevic, Eva J.

doi:10.1039/p29840001077

Cited by 7 publications

(8 citation statements)

References 5 publications

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“…Since P-substituents cause larger rate accelerations in the ring closure of the product ureido acids than a-substituents, we concluded previously that this is an exhibition of the reverse gem-dimethyl effect because the transition state is a looser structure than the initial ring. 6 The acid-catalysed cyclization (Scheme 1) of 3-(3-pheny1ureido)propanoic acids (PUA) offered an opportunity…”

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confidence: 99%

Leffler relationship of the gem-dimethyl effect

Blagoeva¹,

Pojarlieff²,

Rachina³

1986

J. Chem. Soc., Chem. Commun.

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confidence: 99%

Leffler relationship of the gem-dimethyl effect

Blagoeva¹,

Pojarlieff²,

Rachina³

1986

J. Chem. Soc., Chem. Commun.

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“…For each compound the first column presents the apparent second or first order rate constant determined in 1 M KOH. However, our earlier work 12 indicates that the observed hydrolysis rates, k 12 , of the parent dihydroorotic acid 1a and its N-methyl derivative 1b in 1 M KOH are determined mainly by k 1 , the rate constant for formation of the tetrahedral intermediate. For the remaining compounds the OH Ϫ catalyzed breakdown of the tetrahedral intermediate (k 1 k 3 /k Ϫ1 ) is rate determining at 1 M KOH.…”

Section: Resultsmentioning

confidence: 95%

“…The alkaline hydrolysis of 1-alkyldihydroorotic acids 1 has been studied previously, 12 to assess the effect on rates of an axial carboxylate group. (This conformational preference is the result of allylic strain: in the parent acid the COOH group is more or Scheme 3 less equally axial and equatorial.)…”

Section: Resultsmentioning

confidence: 99%

“…(a) N-Methyl and N-ethyl derivatives. The rates of hydrolysis of dihydroorotic acids 1a, 1b and 1c, reported before, 12 were followed by monitoring the decrease of the absorbance of the dianion at 238 nm. In the case of 1b and 1c, on standing the subsequent increase of absorbance with a λ max at 234 nm showed that the formation of the respective hydantoinacetic acids took place at a considerably slower rate.…”

Section: Kinetic Measurementsmentioning

confidence: 99%

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Thorpe–Ingold effects in cyclizations to five-membered and six-membered rings containing planar segments. The rearrangement of N(1)-alkyl-substituted dihydroorotic acids to hydantoinacetic acids in base

Kaneti

Kirby²,

Koedjikov

et al. 2004

Org. Biomol. Chem.

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While the gem-dimethyl effect (GDME) is quantitatively similar for cyclizations to cyclopentane and cyclohexane rings and their homomorphs, in systems containing planar segments the GDME is stronger for the formation of five-membered rings. Planar pentagons have smaller angles than planar hexagons and their formation is helped by the decrease in the potential internal bond angle caused by substituents, as suggested by Thorpe and Ingold for small rings. The phenomenon is illustrated with crystal structure data on five-membered hydantoins and six-membered dihydrouracils containing four-atom planar segments. Such a Thorpe-Ingold effect explains the rearrangement in base of N-alkyl substituted dihydroorotic acids 1 to hydantoinacetic acids 3. The reaction involves initial hydrolysis to N-(N-alkylcarbamoyl)aspartic acids 2 and their subsequent cyclization. The unsubstituted N-carbamoylaspartic acid 2a is stable in 1 M KOH, the N(1)-methyl and ethyl compounds 2b and 2c are in equilibrium with the hydantoinacetic acids 3, while the cyclization of the N(1)-isopropyl and cyclohexyl derivatives 2d and 2e is irreversible. Experimental data on equilibria and pK(a)s for ionization of the carboxy and NH groups allow equilibria and rates involving the N-unsubstituted compounds to be estimated and compared with those for the N-alkyl derivatives. The strongest effect is observed on the equilibrium [3(2-)]/2[(2-)], where substitution of H by methyl increases K 600-fold. In vitro the kinetic regioselectivity for acid catalyzed cyclization of N-carbamoylaspartic to hydantoinacetic acid against dihydroorotic acid is only 10:1. This, together with the weaker acidity of the remote carboxyl group, favours cyclization to dihydroorotic acid under biological conditions.

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“…At higher pH values, there is also ionization of the DHU with its pKoDHu = 11.74 (Koedjikov et aL, 1984). Let .…”

Section: Rhlg-closing Reactionmentioning

confidence: 99%

Hydrolysis of Dihydrouridine and Related Compounds

House

Miller

1996

Biochemistry

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Dihydrouridine is absent from the tRNA of almost all hyperthermophiles and most Archaea but is ubiquitous in the tRNA of Eubacteria and Eukaryotes. In order to investigate whether this could be due to instability, the rate of ring opening of dihydrouridine was measured between 25 and 120 °C. The dihydrouridine ring is stable at 25 °C, but the half-life at 100 °C and pH 7 is 9.1 h, which is comparable to the doubling time of hyperthermophiles. This suggests an explanation for the absence of dihydrouridine from the tRNA of hyperthermophiles. The rates of ring opening of dihydrouracil, dihydrothymine, and 1-N-methyldihydrouracil were measured at 100 °C and pH 6-9, as were the equilibrium constants for ring closure of the ureido acids to the dihydrouracils. The pH rate profiles for ring opening and ring closing were calculated from the data. Possible roles for dihydrouracils in the pre-RNA world are discussed.

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β-Ureido acids and dihydrouracils. Part 15. Effect of allylic strain on ring opening of 1,6-disubstituted dihydrouracils

Cited by 7 publications

References 5 publications

Leffler relationship of the gem-dimethyl effect

Leffler relationship of the gem-dimethyl effect

Thorpe–Ingold effects in cyclizations to five-membered and six-membered rings containing planar segments. The rearrangement of N(1)-alkyl-substituted dihydroorotic acids to hydantoinacetic acids in base

Hydrolysis of Dihydrouridine and Related Compounds

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