Leaving groups, active

Apart from glycosyl acetate and benzoate donors, more elaborate O-carbonyl derivatives offer potential for distinct modes of anomeric leaving group activation. Many of these donors (Scheme 3.21) involve activation of an anomeric O-carbonyl derivative 134 at a remote functional group (Y). The adivated remote functionality, in turn,... 

Another example of leaving group activation is the utilization of S-adenosyl-methionine rather than methionine in methylation reactions. A relatively basic thiolate anion has to be expelled from methionine, while the nonbasic neutral sulfur is displaced from the activated derivative (equation 2.68) ... 

Now let us turn to the effect of solvent on leaving-group activity. Examples of the pertinent experimental data for Sw2 reactions of charge type 1 are shown in Table 4.8. As we would predict from the previous discussion for reactions of... 

Bronsted coefficient (Plg) is around 0.7. Thus, Lewis acid activation, metal-hydroxide activation and leaving-group activation could add up to over 1017-fold rate acceleration for DNA hydrolysis. The pseudo-first order rate constant for hydrolysis of a phosphate diester bond of DNA has been estimated to be about 1(T19 s"1 at neutral pH and 25 °C [13]. A 1017-fold rate acceleration for hydrolyzing DNA would reduce the half-life of the phosphate diester bond from billions of years to about a minute or two. 

Leaving group activation. There is evidence that RTA activates the adenine leaving group for departure by protonation. The large inverse 7- N KIE was evidence that N7 is protonated in the RTA-oxocarbenium ion-adenine complex. The pH profile of RTA activity against A-10 gave evidence for protonation of Nl. The pKa value for Nl of a non-base-paired adenine is near 4. The fccat/ M versus pH... 

---