Synergistic effect of iodine and neighboring amine groups on thioester deacylation

Intramolecular Catalysis of Thiol Ester Hydrolysis by a Tertiary Amine and a Carboxylate

“…This technique has been used previously by Heller et al. 11c and us 4 to test for the process of S to N acetyl transfer that could generate reversibly formed thiolates during the hydrolysis of the acetyl thioesters of 1 and 2 . We observe that the appearance of the Ellman's anion accompanying the hydrolysis of 12 does not depend on the [Ellman's reagent], and from the data in Table , the rate of generation of the Ellman's anion is identical to the rate of disappearance of 12 .…”

“…It is therefore clear that in order for thioester intermediates such as 7 to be hydrolyzed rapidly to regenerate the starting catalyst, some sort of intramolecular catalysis by the pendant amine (or carboxylate in the case of attack of 4 and 6 ) needs to be operative. Although the enzymatic deacylation is believed to occur via such a general base assisted delivery of H 2 O by the active site His-imidazole to the thio acyl enzyme, few small molecule analogues for that process are available. − Bruice 11a and Fife and DeMark 11b have shown that thioesters 8 and 9 undergo rapid intramolecular attack of the imidazole units to give 8a and 9a which subsequently undergo rapid hydrolysis. These findings fit nicely with the general rule that thioesters are not particularly susceptible to attack by oxygen nucleophiles, but are rapidly attacked by nitrogen nucleophiles. 10b, There are few examples where intermolecular general base catalysis of thioester hydrolysis is documented 11c,, and, to our knowledge, even fewer where intramoleular general base catalysis is observed.…”

“…Although the enzymatic deacylation is believed to occur via such a general base assisted delivery of H 2 O by the active site His-imidazole to the thio acyl enzyme, few small molecule analogues for that process are available. − Bruice 11a and Fife and DeMark 11b have shown that thioesters 8 and 9 undergo rapid intramolecular attack of the imidazole units to give 8a and 9a which subsequently undergo rapid hydrolysis. These findings fit nicely with the general rule that thioesters are not particularly susceptible to attack by oxygen nucleophiles, but are rapidly attacked by nitrogen nucleophiles. 10b, There are few examples where intermolecular general base catalysis of thioester hydrolysis is documented 11c,, and, to our knowledge, even fewer where intramoleular general base catalysis is observed. Given the widely held view that general base assistance of the hydrolysis of the cysteine protease acyl enzymes is a facile process, it is surprising that so few small molecule examples of this process exist, the most notable being the hydrolyses of the acetyl thioesters of 1 and 2 4,13 which can be taken as reasonable models for the chemistry believed to occur in the enzymatic active site.…”

3-Cyclohexylaminopropane-1-sulfonic acid hemihydrate

“…CAPS (3-cyclohexylaminopropane-1-sulfonic acid) is a widely used (Zaitseva et al, 2004) biological buffer (pK a = 10.4; Roy et al, 1997) presenting a useful pH range between 9.8 and 11.0. As is commonly found for aminosulfonic acids (Wouters & Stalke, 1996;Kim et al, 1979Kim et al, , 1973aDoi et al, 1983;Yokoyama et al, 2003;Clarke & Steward,1977;Ueoka et al, 1972), CAPS crystallizes as a zwitterion with the acid proton transferred to the N atom.…”