Regioselective direct C-H arylations of protected uracils. Synthesis of 5- and 6-aryluracil bases.

A new regioselective synthesis of 5- and 6-aryluracil bases based on direct C-H arylations of diverse 1,3-protected uracils has been developed. Benzyl-protected uracils were selected as the most practical in terms of stability during the arylation and facile cleavage of the benzyl groups. Pd-catalyzed C-H arylations in the absence of CuI gave preferentially 5-aryl-, whereas the reactions in the presence of CuI gave 6-aryl-1,3-dibenzyluracils.

[The correlation of results of breath analysers and laboratory blood examinations of blood-ethanol concentration (Czech and Slovak study)].

The target of this study was to compare the results of breath analysers and "lege artis" laboratory blood examinations when determining alcohol levels. This was then used to determine whether any differences exist between the two methods, and how large these differences are. 610 cases from 11 workplaces in the Czech Republic and Slovakia were analysed.

Intramolecular direct C-H arylation approach to fused purines. Synthesis of purino[8,9-f]phenanthridines and 5,6-dihydropurino[8,9-a]isoquinolines.

Intramolecular C-H arylations were employed as a key step in the synthesis of hitherto unknown fused purine systems: 13-substituted purino[8,9-f]phenanthridines and 11-substituted 5,6-dihydropurino[8,9-a]isoquinolines. The purino[8,9-f]phenanthridines were prepared in moderate yields by double C-H arylations of 9-phenylpurines with 1,2-diiodobenzene or, more efficiently, by consecutive Suzuki coupling of 9-(2-bromophenyl)purines with 2-bromophenylboronic acid followed by intramolecular C-H arylation. 5,6-Dihydropurino[8,9-a]isoquinolines were prepared in quantitative yields by intramolecular C-H arylations of 9-(2-chlorophenethyl)purines.

Synthesis of 6,8,9-tri- and 2,6,8,9-tetrasubstituted purines by a combination of the Suzuki cross-coupling, N-arylation, and direct C-H arylation reactions.

Novel practical methodology of synthesis of a several types of di-, tri-, and tetraarylpurine derivatives by a combination of regioselective Suzuki cross-coupling reactions and/or Cu-catalyzed N-arylation with direct C-H arylations was developed. 6,8-Diaryl- and 2,6,8-triaryl-9-isopropylpurines were prepared by one or two cross-couplings of 6-chloro- or 2,6-dichloro-9-isopropylpurine with arylboronic acids followed by Pd-catalyzed C-H arylation by aryl halides to position 8. 6-Chloropurine and adenine underwent Cu-catalyzed N-arylation to position 9 with boronic acids, followed by cross-coupling with AlMe3 and/or C-H arylation to obtain 8,9-diaryl-6-methylpurines or 8,9-diaryladenines (accompanied by products of partial N-arylation of adenine in position 6).

The first direct C-H arylation of purine nucleosides.

Pd-catalyzed direct C-H arylation of unprotected purine nucleosides with aryl iodides at position 8 was developed to allow a straightforward single-step introduction of diverse aryl groups.

Direct C-H arylation of purines: development of methodology and its use in regioselective synthesis of 2,6,8-trisubstituted purines.

[Structure: see text] Direct C-H arylation of purines to position 8 by diverse aryl iodides was achieved with Pd catalysis in the presence of CuI and Cs2CO3. The methodology is general and efficient and was applied in the consecutive regioselective synthesis of 2,6,8-trisubstituted purines bearing three different C-substituents in combination with two cross-coupling reactions.

Palladium-catalyzed borylation of phenyl bromides and application in one-pot Suzuki-Miyaura biphenyl synthesis.

The coupling reaction of pinacolborane with various aryl bromides in the presence of a catalytic amount of Pd(OAc)(2) together with DPEphos as ligand and Et(3)N as base provided arylboronates. High yields were obtained in the case of electron-donor substituted aryl bromides. The direct preparation of arylboronates allowed the one-pot, two-step synthesis of unsymmetrical biaryls in high yields.

[[Aortic reconstruction in neonates with hypoplastic left heart syndrome] ].

The surgical technique and tactics of the Norwood operation in neonates with hypoplastic left heart syndrome represent a surgical challenge. The Norwood operation was performed from the midline sternotomy approach, in extracorporeal circulation and deep hypothermic circulatory arrest was used for reconstruction of the hypoplastic aorta. Operation consisted of reconstruction of the "neoaorta" and the aortic arch from the original hypoplastic ascendent aorta, pulmonary trunk and a patch cut from a pulmonary homograft or pericardium, excision of the atrial septum and an arterial shunt from a Goretex vascular graft 3.

[Occult fibrin production during surgery in cyanotic congenital heart defects and extracorporeal circulation].

In 10 patients with complex cyanotic congenital defects detailed coagulation examinations were made at the beginning and end of the extracorporeal circulation after neutralization of heparin by protamine and the results were compared with a control examination, made before general heparinization, after introduction into general anaesthesia. The authors examined the activated period of blood (ACT) by means of testing tubes with a celite activator (Hemochron) as well as the HR-ACT test with a kaolin activator (Medtronic) for comparison of the results. The authors assessed quantitatively plasma levels of heparin, antithrombin III and fibrinopeptide A which is a sensitive indicator of intravascular coagulation.

[Primary repair of interrupted aortic arch in neonates].

In the Kardiocentrum, University Hospital Motol, Prague, protocol of the primary repair of interrupted aortic arch was introduced, and between 1993-1997, 15 neonates aged 1-26 days (median 5 days) were operated on. Treatment with prostaglandins E for maintenance of the ductal patency, correction of metabolic acidosis, and treatment of all complications were necessary before surgery. The correction was performed from the midline sternotomy approach, in extracorporeal circulation and deep hypothermia with circulatory arrest.

[Combined methods for economic blood utilization in cardiac reoperations in children].

During 47 re-operations on the open heart the authors used the method of autotransfusion, predeposition of the patient's blood and intravenous administration of aprotinin to reduce postoperative haemorrhage and blood consumption. The patients were classified according to the methods or their combinations used into three groups and the authors compared, using statistical methods the blood losses, blood consumption, haemolysis, renal function and the effect of the methods used on the morbidity. The results were compared with a control group where the mentioned methods of economizing on blood were not used.

Determination of nitrate by conversion to nitrite using Paracoccus denitrificans.

A new method of determination of nitrate was developed, utilizing the nitrate reductase activity of Paracoccus denitrificans in which a further reduction of nitrate is blocked either by a mutation affecting formation of cytochromes c or by inhibition of the electron flow to nitrite reductase by mucidin. After deproteinization of the sample with zinc acetate the nitrite produced is determined colorimetrically.

Removal of nitrate from water by cells of Paracoccus denitrificans in a membrane flow reactor.

A new type of flow bioreactor designed to remove nitrate from water was developed. Denitrification activity of native Paracoccus denitrificans cells was used, the cells being separated from the refined medium by a semipermeable membrane. Relationships between the degree of nitrate conversion and the denitrification rate, on the one hand, and the volume flow rate and the amount of biomass, on the other, together with the results concerning denitrification during closed-circuit recirculation of the medium are discussed.

Use of uridine rescue to enhance the antitumor selectivity of 5-fluorouracil.

We examined the ability of uridine to increase the therapeutic index of 5-fluorouracil (FUra) against C57BL/6 X DBA/2 F1 mice bearing a Day 1 B16 melanoma or L1210 leukemia. FUra (400, 600, or 800 mg/kg, i.p.

Uridine rescue from the lethal toxicity of 5-fluorouracil in mice.

To determine the relationship between 5-fluorouracil (FUra) toxicity and its RNA- and DNA-directed actions we examined the ability of continuous SC infusions with uridine (Urd), thymidine (dThd), or deoxyuridine (dUrd) to rescue mice from the lethal toxicity of FUra. Male B6D2F1 mice were treated with a single IP injection of FUra (800 mg/kg) followed in 24 h by a 5-day infusion with either 0.9% NaCl or Urd (0.

Biochemical and pharmacologic study of therapeutic synergism with cyclophosphamide plus methotrexate in murine L1210 leukemia.

The combination of cyclosphosphamide (CP) plus methotrexate (MTX) was found to be therapeutically synergistic against the L1210 ascites tumor. After inoculation with 1 x 10(6) L1210 cells to (C57BL/6 x DBA/2)F1 mice, ip administration of CP (200 mg/kg on Day 5) plus MTX (15 mg/kg on Days 5, 7, 9, and 11) resulted in a significant increase in mean lifespan, compared to optimal treatment with either CP or MTX alone. The contribution of the single, simultaneous dose of CP plus MTX on Day 5 to therapeutic synergism was examined.

Effect of concurrent calcium leucovorin infusion on 5-fluorouracil cytotoxicity against murine L1210 leukemia.

We examined the effect of concurrent SC infusion of calcium leucovorin (LV) on the action of 5-fluorouracil (FUra) against mouse L1210 leukemia implanted either SC or IP. Mice bearing the SC tumor treated with FUra (100 mg/kg, IP, day 1) plus infusion with either LV (11.5 mg .