Hydroxyls acylation

Prepared by passing phosgene into a solution of trichloroethanol in benzene-diethylaniline, this stable chloroformate acylates hydroxyl and amino groups in pyridine at room temperature or under Schotten-Baumann conditions (1-3).1 The protective group is removed by treatment with zinc dust in methanol. The group is stable to the conditions of Sarett and of Jones oxidations, to dioxane-HCl, to CF3-... 

Various refined, modified or otherwise processed grades of commercial lecithin are available (e.g. fractionated, phosphorylated, acylaled, hydroxylated and hydrogenated), with consequent differences in composition and physical properties. Liquid, plastic or free-flowing forms can be made. Modified lecithins can function as both oil-in-water and water-in-oil emulsifiers. Hydrogenated varieties have reduced proportions of unsaturated carbon chains in the phospholipids, and are therefore more stable towards oxidation (Table 12.46). 

Carbatricobalt decacarbonyl cation easily acylates hydroxyl, amino, and mercaptan groups. The introduction of 3 Co-atoms in this manner at one specific side of biological macromolecules can facilitate structure determination e. g. by X-ray crystallography . 

After this advance it was observed that mutants blocked before shikimic acid accumulated earlier intermediates. One of these was identified to be 5-dehydroshikimic acid ( 4)- The isolated compound was determined to be a seven-carbon monocarboxylic acid (pif, 3.2) with two acylable hydroxyl groups. The compoimd is levorotatory and has an absorption band in the ultraviolet. Besides the chemical evidence, the fact that the compound could be converted to shikimic acid by mutants that accumulate the latter, strongly supports the conclusion that this intermediate is dehydroshikimic acid. Purification of dehydroshikimic acid could be followed easily siuce it is converted to shikimic acid on autoclaving. 

Explain why esters react with hydroxylamine (NH2OH) to give hydroxamic acids rather than 0-acyl hydroxyl amines. 

As a catalyst for ester and amide formation from acyl chlorides or anhydrides, 4-(di-methylamino)pyridine has been recommended (DMAP G. Hdfle, 1978). In the presence of this agent highly hindered hydroxyl groups, e.g. of steroids and carbohydrates, are acylated under mild conditions, which is difficult to achieve with other catalysts. 

Carboxyl and acyl groups take precedence over the phenolic hydroxyl m deter mining the base name The hydroxyl is treated as a substituent m these cases... 

Acylatmg agents such as acyl chlorides and carboxylic acid anhydrides can react with phenols either at the aromatic ring (C acylation) or at the hydroxyl oxygen (O acylation)... 

On reaction with acyl chlorides and acid anhydrides phenols may undergo either acylation of the hydroxyl group (O acylation) or acylation of the ring (C acylation) The product of C acylation is more stable and predominates under conditions of thermodynamic control when alu mmum chloride is present (see entry 6 m Table 24 4 Section 24 8) O acylation is faster than C acylation and aryl esters are formed under conditions of kinetic control... 

The alcohol groups of carbohydrates undergo chemical reactions typical of hydroxyl functions They are converted to esters by reaction with acyl chlorides and carboxylic acid anhydrides... 

Acylation (Section 25 22) Esterifi cation of the available hydroxyl groups occurs when carbohydrates are treated with acylating agents... 

Once formed cholesterol undergoes a number of biochemical transformations A very common one is acylation of its C 3 hydroxyl group by reaction with coenzyme A derivatives of fatty acids Other processes convert cholesterol to the biologically impor tant steroids described m the following sections... 

Acyl Halides. Acyl halides, in which the hydroxyl portion of a carboxyl group is replaced by a halogen, are named by placing the name of the corresponding halide after that of the acyl radical. When another group is present that has priority for citation as principal group or when the acyl halide is attached to a side chain, the prefix haloformyl- is used as, for example, in fiuoro-formyl-. 

Acetals are readily formed with alcohols and cycHc acetals with 1,2 and 1,3-diols (19). Furfural reacts with poly(vinyl alcohol) under acid catalysis to effect acetalization of the hydroxyl groups (20,21). Reaction with acetic anhydride under appropriate conditions gives the acylal, furfuryUdene diacetate... 

The primary and secondary alcohol functionahties have different reactivities, as exemplified by the slower reaction rate for secondary hydroxyls in the formation of esters from acids and alcohols (8). 1,2-Propylene glycol undergoes most of the typical alcohol reactions, such as reaction with a free acid, acyl hahde, or acid anhydride to form an ester reaction with alkaU metal hydroxide to form metal salts and reaction with aldehydes or ketones to form acetals and ketals (9,10). The most important commercial appHcation of propylene glycol is in the manufacture of polyesters by reaction with a dibasic or polybasic acid. 

The synthesis of 2,4-dihydroxyacetophenone [89-84-9] (21) by acylation reactions of resorcinol has been extensively studied. The reaction is performed using acetic anhydride (104), acetyl chloride (105), or acetic acid (106). The esterification of resorcinol by acetic anhydride followed by the isomerization of the diacetate intermediate has also been described in the presence of zinc chloride (107). Alkylation of resorcinol can be carried out using ethers (108), olefins (109), or alcohols (110). The catalysts which are generally used include sulfuric acid, phosphoric and polyphosphoric acids, acidic resins, or aluminum and iron derivatives. 2-Chlororesorcinol [6201-65-1] (22) is obtained by a sulfonation—chloration—desulfonation technique (111). 1,2,4-Trihydroxybenzene [533-73-3] (23) is obtained by hydroxylation of resorcinol using hydrogen peroxide (112) or peracids (113). 

Liquid crystal polyesters are made by a different route. Because they are phenoHc esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenoHc hydroxyl groups are acylated with a lower aHphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxyHc acid, sometimes in the presence of a catalyst. The phenoHc polyester forms readily as the volatile lower acid distills from the reaction mixture. Many Hquid crystal polymers are derived formally from hydroxyacids (97,98) and thein acetates readily undergo self-condensation in the melt, stoichiometric balance being automatically obtained. 

Several semisynthetic maytansinoids have been prepared by acylating the C-3 hydroxyl group of maytansinol. Some of these derivatives have antiprotozoal and antitumor activity similat to maytansine (104) and ansamitocin P-3 (127) (52,254). 3-Epimaytansinoids have been synthesized and were not biologically active (255). 

The antitumor activity of geldanamycin and its derivatives appears to result from inhibition of DNA synthesis whereas RNA synthesis is not affected (261). The antitumor activity of the maytansinoids also appears to result from the inhibition of DNA synthesis. The mechanism of action of maytansine (104) has been hypothesized to be the acid catalyzed loss of water from the C-9 hydroxyl group of the carbinolamide to form a reactive acyl imine intermediate, which reacts rapidly with nucleophiles on the bases of DNA (262). 

Sahcyhc acid can be converted to sahcyloyl chloride [1441 -87-8] hy reaction with thionyl chloride in boiling ben2ene. The formation of acyl haUde may also extend to reaction with the phenoHc hydroxyl. The reaction with phosphoms tri- and pentachlorides is not restricted to the formation of the acid chloride. Further interaction of the phosphoms haUde and the phenoHc hydroxyl results in the formation of the phosphoric or phosphorous esters. 

Esters of the phenohc hydroxyl are obtained easily by the Schotten-Baumaim reaction. The reaction ia many cases iavolves an acid chloride as the acylating agent. However, acylation is achieved more commonly by reaction with an acid anhydride. The single most important commercial reaction of this type is the acetylation of sahcyhc acid with acetic anhydride to produce acetylsahcyhc acid [50-78-2] (aspirin). 

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