Reduced Selectivity

In preparations whose intracellular space is not accessible,permeability ratios can be determined from differences, AErev, of reversal potential on changing the external cation concentration. Thus in frog muscle fibers treated with veratridine Pnh4/Pns=0.67 as compared to 0.11 in unmodified channels (Leibowitz et al. 1987). In frog nerve fibers treated with the alkaloid mixture veratrine PNa PNH4 PK= 1.0 0.61 0.29 was determined (Naumov et al. 1979), compared with control values for this preparation of 

In neuroblastoma cells (NlE-115) selectivity of modified channels has been derived from influx measurements of radioisotopes and Rb and of [ Clguanidinium and [ C]methylamine in relation to that of Na+, which yielded for 10 iM veratridine 0.39, 0.12, 0.35, 0.06, respectively, as compared to Hille s (1971,1972) permeability ratios for unmodified channels in frog nerve of 0.086,0.012,0.13,0.07. Coactivation with 1 xM ATX II or 10 nM LqTX does not fundamentally change the relations (Frelin et al. 

Selectivity has also been determined from half-lives of cation equilibration of vesicles containing reconstituted Na channels in the presence of veratridine whereby fluxes of isotopes K+, Rb+, and Cs+ were compared with those of Na+. The ratios were 0.83,0.50, and 0.38, respectively, indicating reduced selectivity (Tanaka et al. 1983). Such flux results, however, cannot be compared directly with permeability ratios obtained from Erev measurements. 

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ZnCl2 is essential. The reaction was utilized in the synthesis of strophanthidin. Only the q, /3-alkene in the a, fi- and 7, (5-unsaturated ketone 51 is reduced selectively[47], Triethoxysilane is another reducing agent of the enone 52 and simple alkenes[48]. 

HydrometaHurgical Processes. The hydrometaHurgical treatments of oxide ores involve leaching with ammonia or with sulfuric acid. In the ammoniacal leaching process, the nickel oxide component of the ore first is reduced selectively. Then the ore is leached with ammonia which removes the nickel into solution, from which it is precipitated as nickel carbonate by heating. A nickel oxide product used in making steel is produced by roasting the carbonate. 

Interferences in the method can reduce selectivity and thus rehabihty of the measurement. Therefore it is important to evaluate the method for interferences and to utilize techniques to reduce their impact as weU as to make them known to the analyst (40). 

A 20-ketone can be reduced selectively in the presence of an 11-ketone. In an example quoted in the previous paragraph the reduction was done in ethanol for 1 hour at room temperature. In f-butyl alcohol, NaBH4 reduces a 20-ketone within 5 minutes reduction of the... 

The reduction of l,4-diene-3,20-diones also proceeds more rapidly at the 20-position, at least in methanol, ethanoF and methanol-di-methylformamide. Under mild conditions, the 11-one of a l,4-diene-3,l 1-dione is reduced selectively by NaBH4, but this reaction is better done by Li[OC(CH3)3]3AlH (see below). The reaction of a 4,6-diene-3,20-dione with NaBH4 in methanol for 2 hours at 20° gives the 3j5-hydroxy-20-one. ... 

There is a complication in choosing a catalyst for selective reductions of bifunctional molecules, For a function to be reduced, it must undergo an activated adsorption on a catalytic site, and to be reduced selectively it must occupy preferentially most of the active catalyst sites. The rate at which a function is reduced is a product of the rate constant and the fraction of active sites occupied by the adsorbed function. Regardless of how easily a function can be reduced, no reduction of that function will occur if all of the sites are occupied by something else (a poison, solvent, or other function). 

Nucleoside N -oxides have proved useful in preventing intramolecular cyclizations during manipulation of the sugar moiety. A key step is the reductive removal of the oxide when needed. In the presence of Raney nickel, the oxide can be reduced selectively even when such easily reduced substituents as iodo are present. Azides, however, are reduced concomitantly with the oxide 105). 

Macaudiere et al. first reported the enantiomeric separation of racemic phosphine oxides and amides on native cyclodextrin-based CSPs under subcritical conditions [53]. The separations obtained were indicative of inclusion complexation. When the CO,-methanol eluent used in SFC was replaced with hexane-ethanol in LC, reduced selectivity was observed. The authors proposed that the smaller size of the CO, molecule made it less likely than hexane to compete with the analyte for the cyclodextrin cavity. 

Contamination of metal with other distillates is largely overcome when reducing selected compounds with Zr since the alkali metal is then the only volatile species. Mixtures of CSHSO4 and Cs2Cr04 react explosively, however, carrying particulates over, unless slow heating rates and a large excess of Zr are employed. 

The benefits refer to the ability to achieve defined thin, highly porous coatings in micro reactors. In combination with the small length scales of the channels, diffusion to the active sites is facilitated. The residence time can be controlled, accurately minimizing consecutive reactions which may reduce selectivity. 

Large-scale reactors have low quantum yields as radiation does not penetrate deeply into the reaction vessel [72, 74]. As a consequence, high-power lamps have to be used causing a lot of excess heat and even posing safety constraints. These energy sources produce locally high quantities of radicals which may not mix thoroughly with the rest of the solution. Therefore, they may not find a second reaction partner, but instead react by themselves. This radical combination reduces selectivity and creates additional heat. 

Several groups have published on structural analogues of (382), one of the earliest being the disclosure of CP 272871 (383) from Pfizer, which displays lower affinity for the CBi receptor than (382), in addition to reduced selectivity over the CB2 receptor subtype. Both (382) and (383) have been shown to act as inverse agonists rather than neutral antagonists in vitro [265]. A recently published patent application from Sanofi-Aventis claims a series of 4-cyanopyrazole analogues of (382), with 42 specific examples [266]. 

Similar cis stereoselectivity was observed in formation of four- and five-membered rings.86 The origin of this stereoselectivity was probed systematically by a study in which a methyl substituent was placed at the C(3), C(4), C(5), and C(6) positions of ethyl 7-bromoheptanoate. Good (>93%) stereoselectivity was noted for all but the C(5) derivative.87 These results are consistent with a chairlike TS with the enolate in an equatorial-like position. In each case the additional methyl group can occupy an equatorial position. The reduced selectivity of the 5-methyl isomer may be due to the fact that the methyl group is farther from the reaction site than in the other cases. 

Alternatively, the (2 + 4)-tropilidene endoperoxide, which is the major product in the singlet oxygenation of cycloheptatriene 30 a) affords on diimide reduction the desired bicyclic peroxide 20. The double bond in the two-carbon bridge is reduced selectively, but on exhaustive treatment with excess diimide, the fully saturated substance is obtained. A number of substituted derivatives have been prepared in this way30). 

Alkynes can often be reduced selectively to the alkene by use of the Lindlar catalyst [Pd on CaC03, partly poisoned with Pb(OAc)2]. Here again SYN stereoselectivity is observed despite the fact that this will lead to the more crowded, thermodynamically less stable, cis-alkene, i.e. (52) rather than (53). 

Rhin(bpy)3]3+ and its derivatives are able to reduce selectively NAD+ to 1,4-NADH in aqueous buffer.48-50 It is likely that a rhodium-hydride intermediate, e.g., [Rhni(bpy)2(H20)(H)]2+, acts as a hydride transfer agent in this catalytic process. This system has been coupled internally to the enzymatic reduction of carbonyl compounds using an alcohol dehydrogenase (HLADH) as an NADH-dependent enzyme (Scheme 4). The [Rhin(bpy)3]3+ derivative containing 2,2 -bipyridine-5-sulfonic acid as ligand gave the best results in terms of turnover number (46 turnovers for the metal catalyst, 101 for the cofactor), but was handicapped by slow reaction kinetics, with a maximum of five turnovers per day.50... 

We recently reported a modified Meerwein-Ponndorf-Verley reduction in which low-boiling alcohols such as EtOH and w-PrOH, but preferably i-PrOH, were used at temperatures near 225 °C in the absence of aluminum alkoxides [42]. The carbonyl moiety of an olefinic aldehyde such as cinnamaldehyde was reduced selectively to the alcohol without the carbon-carbon double bond being affected (Scheme 2.7). Since base was not present, aldol and Claisen-Schmidt condensations were avoided. 

Aryl halides can also be reduced by tin hydrides76,77, although these reactions always require initiators because the stronger C—X bonds in aryl halides are less reactive than the C—X bonds in alkyl halides. In fact, a series of meta- and para-substituted bromobenzenes, where X is either meta- or para-CH3O-, C=N, Cl, F, CF3, CH3, Bu-f or 2,6-dichloro, have been reduced by tributyltin deuteride (equation 60). It is worth noting that the more reactive bromide is reduced selectively in the presence of the less reactive chloride and fluoride groups (equation 61). 

Halides in heterocyclic compounds can also be reduced selectively by tin hydrides. For example, the more reactive chlorine in a fluorinated aziridine can be reduced readily using very mild conditions and without a catalyst75. Again, the more reactive chlorine is reduced preferentially (equation 67). 

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