Polycyclic ureas

The Hill reaction has served as a target for structure-activity studies with phenylureas, iV-phenylcarbamates, polycyclic ureas, acylanilides, s-triazines, uracils, dihalogenated benzoni-... 

Moreland and Hill, in an earlier investigation (1963) of the photochemical activity of several polycyclic ureas, found that noruron has the strongest 50% Hill reaction inhibiting efiect, 4.0 10 mole/dm. The Hill reaction inhibition of diuron is 3.3 10 mole/dm, thus being somewhat higher than that of cyclic ureas. 

Moreland and Hill attribute the weaker inhibiting effect of polycyclic ureas to their higher lipophilicity, their less favourable special configuration, and to the absence of resonance interaction between the ring system and the amino nitrogen. 

Such reactions are also possible in vitro, as several mild oxidizing agents are at hand nowadays. Thus, the Dess-Martin periodinane (DMP) [50] has been proven to be a versatile and powerful reagent for the mild oxidation of alcohols to the corresponding carbonyl compounds. In this way, a series of new iodine(V)-mediated reactions has been developed which go far beyond simple alcohol oxidation [51], Ni-colaou and coworkers have developed an effective DM P-mediated domino polycy-clization reaction for converting simple aryl amides, urethanes and ureas to complex phenoxazine-containing polycycles. For example, reaction of the o-hydroxy anilide 7-101 with DMP (2 equiv.) in refluxing benzene under exposure to air led to polycycle 7-103 via 7-102 in a yield of 35 % (Scheme 7.28) [52]. 

A double tethered Biginelli reaction was carried out on the simple five-membered urea aldehyde 305 that reacted with the aliphatic and aromatic bis-ketoesters 306 and 307 giving compounds 308 and 309, respectively, in good yield, albeit with a diasteromeric ratio of 1 3. A series of different polycyclic bis-guanidines resembling betzelladine alkaloids were prepared <2003OL4485>. 

The reactions of thiourea and guanidine with cycloalkanones are carried out in the same manner [101]. But it is worthwhile noting that muticomponent reactions of urea-like compounds with ketones, containing an activated methyl or methyle-negroup, often do not stop after the formation of a pyrimidine ring. In fact numerous derived condensation processes can lead to more complicated polycyclic compounds, which are especially typical for the reaction of cycloalkanones [101]. 

Polycyclic compound 478, which forms stable complexes with urea, guanidine, amidines and their derivatives, is covered by patents (1991USP15030728, 1994USP5283333). These complexes were used in a biological investigation. Receptor betaine molecule 479 was constructed for diagnostic tests for blood (serum) creatinine and renal insufficiency. 

The finding that aromatic diamines (Fig. 12.14) fit inside the narrow hydrophobic pocket of cyclophilin [203] has opened the way to the development of achiral polycyclic compounds which inhibit PPIase activity with submicromolar affinities. The symmetric bis-urea 24 (IC50 = 0.49 jamol Ir1) was the most potent inhibitor in... 

Monoacylation of 2,3-diaminoquinoxalines has been achieved by reaction with an acid anhydride in THF. Under more vigorous conditions reaction of 2,3-diaminoquinoxalines with acid anhydrides results in ring closure to an imidazo[ ]quinoxaline. Similar ring closures have been carried out with aldehydes, acyl halides, formic acid, orthoesters, and urea. Polycyclic compounds have also been prepared from 2,3-diaminoquinoxaline by reaction with 1,-2-dicarbonyl compounds and 1,2-diamines, as illustrated in Scheme 7. 

Urethanes (72) and ureas (73) can also be used to produce novel polycycles when exposed to DMP (2). 

Although the syntheses of compounds containing phosphorus-phosphorus bonds are well established, the incorporation of this diatomic unit into polycyclic molecules is not easy to accomplish. The method presented here is a single-step reaction starting with silyl-substituted urea and phosphorus trichloride. Variation of the urea substituents and the use of RPCI2 instead of PCI, demonstrate the scope of this reaction, which leads to bicyclic —X P as well as spirobicyclic... 

When the urea-hydrogen peroxide system was allowed to react with 1 -adamantaneamine, 1-nitroadamantane was successfully obtained in 26% yield. The slight improvement in the product yield compared with the cyclohexyl system reflects the greater reactivity of the polycyclic adamantyi hydrocarbon. 

J.H.T. Luong, The combined effect of acetonitrile and urea on the separation of polycyclic aromatic hydrocarbons nsing dioctyl snlfosnccinate in electrokinetic chromatography. Electrophoresis, 19, 1461-1467,1998. 

X 10 kg. Analyses of interstellar dust clouds and heavenly bodies fotmd on Earth, such as the Murchison meteorite, showed the presence of a variety of important prebiotic compotmds. such as amino acids, ureas, alcohols. aldehydes, purines, polycyclic aromatic hydrocarbons (PAH), and organic acids,"" highlighting the significance of extraterrestrial carbon delivery to Earth. 

FURAN Combination resins of Phenol Urea Furfuryl alcohol Formaldehyde Particulate matter - soot from the incomplete combustion of the carbon based resins Carbon oxides Phenol, cresols and xylenols Formaldehyde Aromatics (inc. polycyclics) Sulphur dioxide Ammonia Aniline Isocyanic acid Methyl isocyanate Odour may occasionally be a problem... 

Most recently. You and co-workers [120] presented a desymmetrization of cyclodienones bearing active methylene groups via a cinchonine alkaloids urea-catalyzed asymmetric Michael reaction, affording polycyclic cyclohexenones in high yields and enantioselectivites (Scheme 5.62). 

A hydroamination/N-sulfonyliminium cyclization cascade was carried out enantioselectively with gold and BINOL-phosphoric acid catalysts to generate fused indole 188. The method can also be extended to furnish lactams with up to 93% ee (13OL4330). Polycyclic indoline 189 was prepared via an indium/TFA-catalyzed tandem cycloannulation of P-oxodithioesters with tryptamine in yields up to 92% (130L1974). Dixon and colleagues utilized an enantioselective Michael addition/iminium ion cyclization of trypt-amine-derived ureas in the synthesis of tetracyclic indole 190 (22 examples, up to 78% yield and 96% ee) (130L2946). 

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