Deacetylation

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

Thus reduction of the 5-thiocyanato group of 151 by zinc (333, 360, 361) or aqueous sodium sulfide (348. 362), hydrolysis of the thiouronium group (7, 363, 364), and deacetylation of the 5-acetylthiothiazole with cold piperidine (365) have been performed to yield the 5-mercapto-thiazole (Scheme 78). It must be pointed out that depending on the experimental conditions, bis(5-thiazolyl(sulfide may be observed as a byproduct (363, 365). Thus 5-amino-4-methylthiazole (152) treated with... 

The cyclization of pentaacetyl-o-gluconic thioamide with chloroacetone and of pentaacetyl-D-galactonic acid thioamide with phenacyl bromide give the corresponding 4-substituted 2-(D-galactopentaacetoxypentyl)-thiazoles (27) (660) but in low yield (23 to 27%) (Scheme 13). The products may be deacetylated in the usual way. These compounds are interesting from a pharmacological point of view. 

If pure isomers are required, the ortho and meta compounds can be prepared by indirect methods. o-Nitrotoluene can be obtained by treating 2,4-dinitrotoluene with ammonium sulfide followed by diazotization and boiling with ethanol. / -Nitrotoluene can be prepared from -toluidine by acetylation, nitration deacetylation, diazotization, and boiling with ethanol. A fairly pure -nitrotoluene, which has been isolated from the isomeric mixture, can be purified further by repeated crystallization. 

Trityl Ethers. Treatment of sucrose with four molar equivalents of chlorotriphenylmethyl chloride (trityl chloride) in pyridine gives, after acetylation and chromatography, 6,1, 6 -tri-O-tritylsucrose [35674-14-7] and 6,6 -di-O-tritylsucrose [35674-15-8] in 50 and 30% yield, respectively (16). Conventional acetylation of 6,1, 6 -tri-O-tritylsucrose, followed by detritylation and concomitant C-4 to C-6 acetyl migration using aqueous acetic acid, yields a pentaacetate, which on chlorination using thionyl chloride in pyridine and deacetylation produces 4,l, 6 -trichloro-4,l, 6 -trideoxygalactosucrose [56038-13-2] (sucralose), alow calorie sweetener (17). 

Acetates. Because of the significant interest in selective acetylation reactions of sucrose, the need for a convenient and unambiguous method of identification has been recognized (34,35). The position of an acetyl group in a partially acetylated sucrose derivative can be ascertained by comparison of its H-nmr acetyl methyl proton resonances after per-deuterioacetylation with those of the assigned octaacetate spectmm. The synthesis of partially acetylated sucroses has generally been achieved either by way of selectively protected derivatives such as trityl ethers and cychc acetals or by direct selective acetylation and deacetylation reactions. 

Starting cellulose, prepared by deacetylation of commercial, medium viscosity cellulose acetate (40.4% acetyl content). 

Naphtho[ 1,2-h]pyran-4-one, 3,6-diacetyl-2-methyl-deacetylation, 3, 713 Naphtho[ 1,2-h]pyran-4-one, 5,6-dihydro-synthesis, 3, 811... 

NQR, 2, 125 Pyridines, acetylalkyl-alkyl deacetylation, 2, 301 Pyridines, acetyltrimethyl-synthesis, 2, 470 Pyridines, acyl-conformation, 2, 162 reactions, 2, 337 Pyridines, alkenyl-ozonolysis, 2, 334 reactions, 2, 334 Pyridines, alkenyldihydro-disproportiation, 2, 62 Pyridines, alkyl-... 

Degradation Decarboxylation, deamination, dehalogenation, dehydroxylation, ring fission, demethoxylation, deacetylation... 

Chlorination of 1-hexyne in acetic acid leads mainly to l,l-dichlorohexan-2-one via chlorination and deacetylation of the initial product, 2-acetoxy-l-chlorohexene. 

An isolated acetoxyl function would be expected to be converted into the alkoxide of the corresponding steroidal alcohol in the course of a metal-ammonia reduction. Curiously, this conversion is not complete, even in the presence of excess metal. When a completely deacetylated product is desired, the crude reduction product is commonly hydrolyzed with alkali. This incomplete reduction of an acetoxyl function does not appear to interfere with a desired reduction elsewhere in a molecule, but the amount of metal to be consumed by the ester must be known in order to calculate the quantity of reducing agent to be used. In several cases, an isolated acetoxyl group appears to consume approximately 2 g-atoms of lithium, even though a portion of the acetate remains unreduced. Presumably, the unchanged acetate escapes reduction because of precipitation of the steroid from solution or because of conversion of the acetate function to its lithium enolate by lithium amide. 

Akiyama, S. IC, and Hamme.s, G. G., 1980. Elementary. step.s in die reaction mechani.sm of die pyruvate dehydrogena.se mnltienzyme complex from Escherichia coli Kinetics of acetylation and deacetylation. Biochemistry 19 4208-4213. 

In the realm of natural product synthesis, Kepler and Rehder utilized the K-R reaction to synthesize ( )-calanolide A (56), a potent non-nucleosidal human irmnunodeficiency virus (HIV-1) specific reverse transcriptase inhibitor. Propiophenone 57 was allowed to react with acetic anhydride in the presence of sodium acetate to afford benzopyranone 58 in 56% yield subsequent deacetylation of 58 gave 59. Flavone 59 was then transformed to ( ) calanolide A (56) over several steps. 

Tire 2-dimethylamino derivatives 147 were prepared by a three-step reaction pathway that comprised (a) methylation of the 2-acetamido derivative 144 with methyl iodide and sodium hydride to 145, (b) mild acid-catalyzed N-deacetylation of 145 to 146, and (c) further methylation of 146 to the 2-dimethylamino compound 147 (90JMC1230) (Scheme 57). 

The reaction of the sodium salts of pyrido[2,3-e]-l,2,4-triazin-3(4//)-one 1-oxide 22 (Y = N) or l,2,4-benzotriazin-3(4//)-one 1-oxide 23 with acetobro-moglucose results in tetra-(9-acetyl derivatives of /3-D-glucopyranosides 24, 25 deacetylation of 25 gives nucleosides 26 (82JHC497). 

Acidic deacetylation of 129 followed by alkaline treatment of the intermediate 130 provided denitrocyclization product 131 in 51% overall yield (77KGS1271). A similar cyclized product was reported to be formed from 2-nitrobenzimidazole (132), which when treated with aziridine, instead of the corresponding aminoethyl derivative, provided 93% of benzimidazo[2,l-fo]imidazole 133 (Scheme 21) (82JMC1342). 

A somewhat more circuitous route is required to prepare sulfonamide-containing pyrimidines unsubstituted at 2. Thus, acylation of the 2-thiomethyl pyrimidine, 147, with the sulfonyl chloride, 88, affords 148. Removal of sulfur by means of Raney nickel (149) followed by deacetylation gives sulformethoxine (113). ... 

Ceftizoxime (83) is structurally of interest in that it lacks any functionality at C-3 and therefore cannot undergo the usual metabolic deacetylation experienced by many cephalosporins. Its synthesis involves condensation of the acid chloride corresponding to ester 74 (74a) with 3-lactam 82. ... 

Caracemide (3) is an antitumor agent. This simple molecule is constructed by reacting acetohydroxamic acid (1) with methylisocyanate (2) promoted by triethylamine. The resulting 0,N-biscarbamate (3), caracemide, is metabolized readily either by deacetylation or by decarba-moylation and its antitumor properties are believed to re.sult from the reactivity of the resulting metabolites with DNA [1]. 

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