Chelation anti-chelate effect

Other papers in the Symposium deal with the antioxidant and hypolipidemic effects of IP6, its chelating effects in heavy metal toxicity, inhibition of renal stones and other beneficial effects such as inhibition of platelet aggregation, inhibition of inflammatory responses (Shamsuddin, 1998). The lipid lowering effect and anti-neoplastic effect of 1P6 were extensively reviewed (Jariwalla, 1999). Hence, 1P6 is a valuable component of rice bran in preventing disease and maintaining health. 1P6 is present at 1.8-2% in rice bran. 

Chelation effects also come into play in the reduction of a,[3-epoxyketones. Both CaCl2 and LaCl3 lead to enhanced anti stereoselectivity.139 The same stereoselectivity is observed with CeCl3 and with Zn(BH4)2.140... 

Scheibel and Adler195) have shown that the anti-malarial effects on the growth of the parasite appear to correlate with the ability of 5,7-dichlorooxine, 5-chloro-7-iodooxine, 5-chlorooxine, 6-hydroxy-l,7-phenanthroline, and 5-chloro-7-(3-diethylaminopropyl-aminomethyl)-8-quinoline didydrochloride to chelate metals. 

Excellent, high diastereoselective control can be achieved with organotin derivatives using potassium hexamethyldisilazanide for deprotonation. As a consequence of the defined enolate geometry by chelation effects, the (/T)-cstcr gives syn-23 as the main product (syn/anti ratio 39 1), whereas the (Z)-esler leads to anti-23 (antijsyn ratio > 40 1)50°. 

The Cram chelation model (sec. 4.7.B) is an example where the chelation effects of the heteroatom influence the rotamer population and, thereby, the selectivity of the reduction. Zinc borohydride [Zn(BH4)2], effectively chelates the carbonyl oxygen and alcohol oxygen atoms in the reduction of 42 and leads to intermediate 43. Transfer of hydride to the carbonyl gave primarily the anti diastereomer, 45 (4 96, 44/45). When the chelating hydroxyl group was blocked as a tert-butyldiphenylsilyl ether (in 46 - sec. 7.3.A.i), reduction with Red-Al (sec. 4.3) led to a reversal in selectivity (96 4, 47/48).The ability to chelate a heteroatom varies with the reagent used. Lithium aluminum hydride shows less selectivity, due in part to poorer coordination with the heteroatom and reduction of 42 gave a 27 73 mixture of 44 and 45,... 

The thiols can act as chelators and bind heavy metal ions through mercaptide formation. The chelation may also involve the amino group. Copper-chelation by penicillamine, changes in copper metabolism and altered concentrations of coppercontaining proteins like ceruloplasmin and altered activity of the copper-dependent superoxide dismutase (an intracellular enzyme for removal of toxic superoxide radicals) may be of importance. Chelation of copper may also increase the prostaglandin E/f ratio, which is assumed to have an anti-inflammatory effect. 

Polansky, J. and Weinreb, B. (1984). Anti-inflammatory agents steroids as anti-inflammatory agpnts. In Pharmacology of the Eye (ed. M.L. Sears) pp. 459-538. Springer Verl, Berlin. Rao, N., Romero, J., Fernandez, M. and Marak, G.E. (1986). Effect of iron chelation on severity of occular inflammation in an animal model. Arch. Ophthalmol. 104, 1369-1371. 

In the discussion of the stereochemistry of aldol and Mukaiyama reactions, the most important factors in determining the syn or anti diastereoselectivity were identified as the nature of the TS (cyclic, open, or chelated) and the configuration (E or Z) of the enolate. If either the aldehyde or enolate is chiral, an additional factor enters the picture. The aldehyde or enolate then has two nonidentical faces and the stereochemical outcome will depend on facial selectivity. In principle, this applies to any stereocenter in the molecule, but the strongest and most studied effects are those of a- and (3-substituents. If the aldehyde is chiral, particularly when the stereogenic center is adjacent to the carbonyl group, the competition between the two diastereotopic faces of the carbonyl group determines the stereochemical outcome of the reaction. 

Entry 10 is an example of the application of chelate-controlled stereoselectivity using TiCl4. Entry 11 also involves stereodirection by a (3-O-methoxybenzyloxy) substituent. In this case, the BF3-catalyzed reaction should proceed through an open TS and the (3-polar effect described on p. 96 prevails, resulting in the anti-3,5-isomer. 

A related effect is noted with a-alkoxyacyl derivatives. These compounds give mainly the anti adducts when a second equivalent of TiCl4 is added prior to the aldehyde.144 The anti addition is believe to occur through a TS in which the alkoxy oxygen is chelated. In the absence of excess TiCl4, a nonchelated cyclic TS accounts for the observed syn selectivity. 

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