Cleavage reactions, base hydrolysis

Hydrolases, it is generally accepted that an enzymatic reaction is virtually reversible, and hence, the equilibrium can be controlled by selecting the reaction conditions. Based on this view, hydrolases, enzymes catalyzing a bond-cleavage reaction by hydrolysis, have been developed as catalyst for the reverse reaction of hydrolysis, leading to polymer production by a bond-forming reaction (9,12). 

Table 3.26 lists illustrative examples of cleavage reactions of support-bound N-aryl-carbamates, anilides, and /V-arylsulfonamidcs. /V-Arylcarbamatcs are more susceptible to attack by nucleophiles than /V-alkylcarbamates, and, if strong bases or nucleophiles are to be used in a reaction sequence, it might be a better choice to link the aniline to the support as an /V-bcnzyl derivative. Entry 7 (Table 3.26) is an example of a safety-catch linker for anilines, in which activation is achieved by enzymatic hydrolysis of a phenylacetamide to liberate a primary amine, which then cleaves the anilide. 

Detailed studies of the base hydrolysis of the dihydroxo-bridged species have not been reported. The hydrolysis of A,A-(en)2-Rh(OH)2Rh(en)24+ to give A,A-(HO)(en)2Rh(OH)Rh(en)2(OH)3+ has been reported to be five times faster at pH 12 than the uncatalyzed (kt) bridge-cleavage reaction. The dihydroxo-bridged species is a weak acid (pK > 12) and the mechanism could either involve cleavage via formation of an oxo-bridged species or via direct attack by hydroxide (217). 

Hydrolysis of a triacylglycerol with water in the presence of either acid, base, or an enzyme yields glycerol and three fatty acids. This cleavage reaction follows the same mechanism as any other ester hydrolysis (Section 22.11). This reaction is the first step in triacylglycerol metabolism. 

The base hydrolysis under harsh conditions very often brings about undesired cleavage of phosphates. In contrast, removal of an o- orp-chlorophenyl protecting group by lV ,iV, iV, /V -tetramethylguanidinium ryn-p-nitrobenzaldoxymate (NBO) (108 equation 65) or syn-pyridin-2-aldoxymate (PAO) (109) is achievable at room temperature and no side reaction occurs. The 8-quinolyl phosphate (110 equation 66) is also hydrolyzed under mild conditions with the assistance of a stoichiometric amount of ZnCb or CuCb salt. ... 

Thiomethyl-PS 6b, prepared from Merrifield s resin la by reaction with thioacetate followed by reduction, can be acylated to give thioesters [263]. The resin-bound thioesters have been converted to silyl enol ethers, which were shown to form aldol products that could be released from the resin by three methods [264], Thus, reduction with lithium borohydride or diisobutylaluminum hydride (DIBAL) gave diols and aldehydes, respectively alternatively, base hydrolysis afforded carboxylic acids. Resin 6b thereby extends the range of functional groups available compared with cleavage of related molecules from an ester anchor. 

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