Uracil ring

Der Uracil-Ring wird in 1,3,10-Trimethyl-flavinium-perchlorat durch Reduktion mit Natriumboranat in Wasser zu dem Hydantoin-Ring umgelagert3. 

P2j Z = 2 DX = 1.43 R = 0.067 for 1269 intensities. The uracil residue is in the anti (63.4°) disposition. The conformation of the D-ribosyl group is 2T3 (176.8°, 37.5°). The orientation about the exocyclic, C-4 -C-5 bond is t (—174.2°). The phenyl and uracil ringsofthe same molecule lie in almost parallel planes, 120 pm apart. The phenyl group is disordered. The uracil ring is sandwiched by the phenyl rings, and vice versa. The 0-1 and N-a atoms of the peptide backbone are hydrogen-bonded to 0-4 and N-3 of atranslationally related uracil to form cyclic dimers. Such interactions serve as models for nucleic acid-protein interactions. [Coordinate errors H(02 ) x should be —1574, instead of —1474 H(Na)2 z should be —145 instead of— 645.]... 

Pd(0)-catalyzed substitution reaction, a novel, mild reduction of a-nitro ester to an amino acid ester with TiCl3, and an improved procedure for uracil ring formation. 

Pyrimidine as the outer ring. Indolizines and their aza analogues fused to a uracil ring are produced in several ways (1) by thermal cyclization of 5-(2,2-dicyanoethenyl)-6-pyrrolidinouracil (Equation 66) <1998JCM502,... 

An efficient preparation of 5-cyanouracils started from JV-ethoxycarbonylcyanoacetamide 47, the carbonyl of the urethane finally being incorporated into the uracil ring... 

A kinetic study of alkaline hydrolysis of reumycin 311 indicated that OH added reversibly to C-5 to form an intermediate 408, which then decomposed to the triazine 409 (88MI2). At high OH concentrations, the rate-limiting step was the attack of OH on C-5 of 311, whereas at low OH concentrations it was the cleavage of the uracil ring in intermediate 408. 

While the effects of internally deposited radionuclides are attributable in most instances to the type and energy of the radiations they emit, their transmutation on decay has also been implicated in certain circumstances, e.g., the severe mutagenicity and lethality caused by decay of iodine-125 in 5-iododeoxyuridine-labelled DNA is attributed in part to rupture of the uracil ring following transmutation of the iodine (Stocklin, 1979). 

Low-molecular-mass thiols such as coenzyme A and protein-bound thiol cofactors such as phospho-pantetheine are present in all cells. Their SH groups can also be oxidized to disulfides and it is of interest that in resting bacterial spores these compounds exist largely as disulfides or mixed disulfides. Upon germination of the spores special enzymes reduce the disulfides.136 Some proteins involved in control of protein synthesis contain SH groups that add covalently to C-6 atoms of a uracil ring in specific mRNA molecules. Control of their state of reduction may also be important.137... 

Hydroxymethyluracil 30, a component of the present-day DNA of Bacillus subtilis bacteriophages [103], was obtained by electrophilic addition of formaldehyde to the C5-C6 double bond of a preformed uracil ring (which is probably the reason for the absence of uracil in the reaction mixture). Thymine was then obtained from 5-hydroxymethyluracil by the hydride shift mechanism shown in Scheme 18 involving formic acid as a product of formaldehyde oxidation. This is the only prebiotic synthesis of thymine so far described starting from one-carbon atom precursors as simple as formamide and formaldehyde. 

Fluorouracil [flure oh YOOR a sil] (5-FU), a pyrimidine analog, has a stable fluorine atom in place of a hydrogen atom at position 5 of the uracil ring. The fluorine interferes with the conversion of deoxyuridylic acid to thymidylic acid, thus depriving the cell of one of the essential precursors for DNA synthesis. 

From the values of the monomer reactivity ratios, the relative reactivity of the monomers toward the growing free radicals derived from MAOThe, MAOA and MAOU (t, a and u, respectively) was estimated (Table 6). As for the growing radical of MAOThe (t), for example, the reactivities of MAOThe and MAOU monomer are equal but higher than that of MAOA monomer in ethanol solution while the reactivities of these monomers are nearly equal in dioxane solution. The copolymerization proceeds predominantly under the influence of base-base pairing between adenine and uracil rings. 

Diazepine-2,4-diones, formation by uracil ring-expansion, 55, 196... 

The hydrolytic lability of N.O-acetals varies widely. One extreme is exemplified by a synthesis of the cyanobacterial hepatotoxin Cylindrospermopsin [Scheme 8.157]345 in which hydrolysis of the oxazolidine ring in 157.1 required HCI in aqueous THF at 85 °C The penultimate step in the synthesis required hydrolysis of two N-MOM groups on the uracil ring but the positively charged guanidi-nium salt 157.3 thwarted a second protonation required for the hydrolysis hence, 12 M HCI at 95 °C was required to secure the product 157 4. 

Figure 13.12. The thymidylate synthase reaction, and its inhibition by 5-fluoro-deoxyuridinemonophosphate (5-FdUMP). a Overview of the reaction, b The catalytic mechanism. The enzyme forms an intermediate in which it is covalently linked to both the substrate (UMP) and, via the latter, to the coenzyme (bottom center). Resolution of this intermediate does not happen with 5-FdUMP because it requires abstractionof the hydrogen normally found in position 5 of the uracil ring.

In addition, substituent effects on the uracil ring have been investigated in photocycloadditions with DBMI [83AG156, 83AG(E)157, 83AG(S)120] (Scheme 32). 

Ambident nucleophiles, such as guanidine, thiourea, and urea attack 1,3-dimethyluracil first at the 6-position. After cleavage of the uracil ring and displacing ring closure, novel pyrimidines are formed extruding di-... 

Instead of the nucleophilic N-atoms, the attempted attack of appropriate carbanions (from acetamides substituted with an electron-withdrawing group) on the C-6 position of dimethyluracil leads to the cleavage of the uracil ring. This reaction splits off dimethylurea and leads finally to the formation of tautomeric pyridine-2,6-diones, such as 2,6-dihydroxynico-tinamide. Similarly, the reaction of 1,3-dimethyl-4-thiouracil with malo-namide proceeds smoothly to give 2-hydroxy-6-mercaptonicotinamide (791A4423 81JOC846) (Scheme 136). 

Another original transformation of a 5-nitrouracil into a 5-carbamoylura-cil was observed on treatment of 1,3-dimethyl-5-nitrouracil with malona-mide in ethanolic sodium ethoxide. In this case, the N(3)—C(4)—C(5) element of the uracil ring is replaced [81TL2409 84JCS(P1) 1859] (Scheme 141). 

The mechanism shown in Scheme 150 suggests that the presence of a terminal nucleophile in the sidechain on a uracil ring enables the ring transformation of uracil into other rings by an intramolecular rearrangement. In fact, in the presence of sodium ethoxide 5-(2-carbamoyI-vinyl)uracil-5-carbohydrazides are easily converted into pyridines and 3-... 

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