Selective deacylation

Benzoates. The selective debenzoylation of sucrose octabenzoate [2425-84-5] using isopropylamine in the absence of solvents caused deacylation in the furanose ring to give 2,3,4,6,1/3/6 -hepta- and 2,3,4,6,1/6 -hexa-O-benzoyl-sucroses in 24.1 and 25.4% after 21 and 80 hours, respectively (54). The unambiguous assignment of partially benzoylated sucrose derivatives was accompHshed by specific isotopic labeling techniques (54). Identification of any benzoylated sucrose derivative can thus be achieved by comparison of its C-nmr carbonyl carbon resonances with those of the assigned octabenzoate derivative after benzoylation with 10 atom % benzoyl—carbonyl chloride in pyridine. 

Hydrolysis of esters and amides by enzymes that form acyl enzyme intermediates is similar in mechanism but different in rate-limiting steps. Whereas formation of the acyl enzyme intermediate is a rate-limiting step for amide hydrolysis, it is the deacylation step that determines the rate of ester hydrolysis. This difference allows elimination of the undesirable amidase activity that is responsible for secondary hydrolysis without affecting the rate of synthesis. Addition of an appropriate cosolvent such as acetonitrile, DMF, or dioxane can selectively eliminate undesirable amidase activity (128). 

As noted in an earlier section of this article, the utility of the cycloamyloses as covalent catalysts is limited by the low reactivity of the catalytically active hydroxyl groups at neutral pH s and by the relatively slow rates of deacylation of the covalent intermediates. In an effort to achieve effective catalysis, several investigators have attempted to selectively modify the cycloamyloses by either (1) introducing an internal catalyst to facilitate deacylation or (2) introducing a more reactive nucleophile to speed acylation and/or deacylation. 

Deacylation of hydrophobic p-nitrophenyl alkanoates Hydroxamic acid and phenyl ester derivatives had alkyl or fluoroalkyl substituents. Rate effects depend on selectivity of binding of fluoro- and hydro-carbon derivatives Kunitake et ai, 1984... 

Representative Experimental Procedures 128 Representative Procedure for Preparation of Cl-Hemiacetal Donors Through a Peracylation-Selective Anomeric Deacylation Sequence 128... 

Sulfacetamide Sulfacetamide, iV -acetylsulfanilamide (33.1.44), is synthesized either by direct alkylation of acetamide with 4-aminobenzenesulfonyl chloride, or by reacting 4-aminobenzenesulfonamide with acetic anhydride and subsequent selective, reductive deacylation of the resulting acetamide 33.1.45 using a system of zinc-sodium hydroxide [37,38],... 

Although many publications have covered the enantioselectivity of lipases in the deacylation step, their enantioselectivity in the acylation step (i.e., towards the acyl donor) has received much less attention. Generally, the selectivity of lipases towards racemic esters or acids is low to moderate [75-77]. Directed evolution and site-directed mutagenesis lead to a significant increase in the selectivity of the wild-type enzymes [78-80]. However, the enantiomeric ratios attained are still well below those typically obtained in kinetic resolutions of secondary alcohols. 

The first enzymatic polymerizations of substituted lactones were performed by Kobayashi and coworkers using Pseudomonas fluorescens lipase or CALB as the biocatalyst [90-92]. A clear enantiopreference was observed for different lactone monomers, resulting in the formation of optically active polymers. More recently, a systematic study was performed by Al-Azemi et al. [93] and Peelers et al. [83] on the ROP of 4-alkyl-substituted CLs using Novozym 435. Peelers et al. studied the selectivity and the rates as a function of the substituent size with the aim of elucidating the mechanism and the rate-determining step in these polymerizations. Enantio-enriched polymers were obtained, but the selectivity decreased drastically with the increase in substituent size [83]. Remarkably for 4-propyl-e-caprolactone, the selectivity was for the (R)-enantiomer in a polymerization, whereas it was S)-selective in the hydrolysis reaction. Comparison of the selectivity in the hydrolysis reaction (Fig. 10b) with that of the polymerization reaction (Scheme 8a) revealed that the more bulky the alkyl substituent, the more important the deacylation step becomes as the rate-determining step. 

Deprotonation of the A -acyl substituent of benzothiazines gives a nucleophile that reacts by deacylation with a second molecule of starting material (Equation 46) < 1980TL3001 >. Such anions also react with ketones in an erythro-selective aldol condensation (Equation 47) <1983TL3883>. The selectivity is due to the formation of a Z-enolate and the reaction was also extended to A -acylphenothiazines. 

The consecutive formation of o-hydroxybenzophenone (Figure 3) occurred by Fries transposition over phenylbenzoate. In the Fries reaction catalyzed by Lewis-type systems, aimed at the synthesis of hydroxyarylketones starting from aryl esters, the mechanism can be either (i) intermolecular, in which the benzoyl cation acylates phenylbenzoate with formation of benzoylphenylbenzoate, while the Ph-O-AfCL complex generates phenol (in this case, hydroxybenzophenone is a consecutive product of phenylbenzoate transformation), or (ii) intramolecular, in which phenylbenzoate directly transforms into hydroxybenzophenone, or (iii) again intermolecular, in which however the benzoyl cation acylates the Ph-O-AfCL complex, with formation of another complex which then decomposes to yield hydroxybenzophenone (mechanism of monomolecular deacylation-acylation). Mechanisms (i) and (iii) lead preferentially to the formation of p-hydroxybenzophenone (especially at low temperature), while mechanism (ii) to the ortho isomer. In the case of the Bronsted-type catalysis with zeolites, shape-selectivity effects may favor the formation of the para isomer with respect to the ortho one (11,12). 

Enzymes are widely recognized as valuable tools for the synthesis of optically active compounds [22]. Thus, lipase-catalyzed acylation or deacylation is one of the most efficient methods for the preparation of optically active alcohols, acids, and esters. Because lipases retain activity and selectivity in non-conventional media such as organic liquids, their use as biocatalysts in enantioselective synthetic reactions has considerably increased. 

Selective Deacylation of Derivatives Containing the Same Type... 

The selective removal of an acyl group at the anomeric center will not be considered here, unless it is accompanied by selective deacylation at another position. Also, the selective removal of O-acyl groups in the presence of N-acyl groups, which is generally achieved without difficulty, is omitted. The material considered here is divided into Subsections based, essentially, on the type of substrate. 

Ammonolysis of perbenzoylated derivatives of mono- and di-saccharides provides interesting examples of selective deacylation. Treatment of the benzoylated nitriles of D-galactonic, D-gluconic, and... 

Further examples of selective deacylation in disaccharide derivatives were provided by the reaction of 2,3,6,2, 3, 4, 6 -hepta-0-acetyl-maltosyl bromide and 2,3,6,2, 3, 4, 6 -hepta-0-acetyllactosyl bromide with pyridine115 the former yielded 3,6,2, 3, 4, 6 -hexa-0-acetyl-maltosylpyridinium bromide, whereas the latter gave 3,3, 4 -tri-0-acetyl- and 3,6,3, 4, 6 -penta-0-acetyl-lactosylpyridinium bromide. 

---