Catechol monoesters

Fig. 8.5. Mechanism postulated for competitive, specific base catalyzed hydrolysis and acyl migration of catechol monoesters, as seen with 4-pivaloyl-L-dopa (8.81) [114a]. Deprotonation (Reactions a and b) accelerates intramolecular nucleophilic attack (Reactions c and d) to form a tetrahedral transition state. The latter is postulated to be the intermediate common to hydrolysis (Reaction e) and acyl migration. 

It is of interest that the mechanism shown in Fig. 8.5 should be applicable to all catechol monoesters, but this is only seen when hydrolysis is comparatively slow. More studies are needed to examine the mechanistic hypothesis presented in Fig. 8.5 and the pharmacokinetic consequences of intramolecular acyl migration in monoesters of catechols. 

One must be careful not to generalize from the above discussion that hydrolysis of pivaloyl esters will always be slow. Indeed, a notable exception may well exist for monoesters of catechols, where intramolecular catalysis accelerates hydrolysis. This was seen for L-3-[3-hydroxy-4-(pivaloyl-oxy)phenyl] alanine (8.81 4-pivaloyl-L-dopa), a potentially valuable prodrug of L-dopa [114], When given to rats and dogs, 4-pivaloyl-L-dopa displayed markedly longer duration of action and a higher bioavailability of L-dopa than the drug itself complete conversion to L-dopa was noted in rat. The... 

Copper(II) reagents for the conversion of catechols and o-benzoquinones to muconic acid monoesters can also be prepared by adding a nucleophile ROH (R = Me, Et, n-Pr, etc. ) to the products of oxidation of CuCl in pyridine [40],... 

The half ester of (E -muconic acid (456) was synthesized in three steps as follows Starting from catechol (457), oxidative cleavage with a peracid led to the (Z,Z)-diacid 458, which was monoprotected via lactonization to provide compound 459, and by treatment with Eschenmoser s base the desired monoester 460 was obtained (Scheme 8.15). 

Tsuji, J., and H. Takayanagi Oxidative Cleavage Reaction of Catechol and Phenol to Monoester of m, . s-Muconic Acid with the Oxidizing Systems of Oz/CuCl, KOH/CuCl2 and KOa/CuCh in a Mixture of Pyridine and Alcohol. Tetrahedron 34, 641 (1978). 

Cuprous chloride pyridine Oxidative catechol ring opening Dicarboxylic acid monoesters... 

The preparation of monoethers of symmetrical dihydroxy aromatic compounds has been reported (Leznoff and Dixit, 1977). The dihydroxy aromatic compounds were bound to a benzoyl chloride support via a monoester bond, reacted with diazomethane, and cleaved from the resin by base hydrolysis. Yields ranged from 20 to 75%, depending on the compound. Catechol and 1,4-dihydroxynaphthalene, although attached to the polymer, did not yield any product. It was found that double-binding to the polymer was minimal and was not the cause of lowered yields. 

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