Acetoxyl group

Possible Interference from Hydroxy and Acetoxyl Groups... 

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. 

An acetoxyl group at C-21, if present, is retained and an a,) -unsaturated ketone system in ring A does not interfere. 

Ordinarily the zinc-acetic acid system will not react with a 21-acetoxy-20-ketone however, if a A -double bond is also present, the 21-acetoxyl group is removed in high yield at room temperature in 3 min. Increasing the time of reaction causes subsequent reduction of the 20-ketone to hydroxyl. 

A direct method for introduction of a C-21 acetoxyl group into a 20-keto-pregnane is by reaction with lead tetraacetate at room temperature. Although originally the reaction carried out in hot acetic acid gave low yields, a careful study by Henbest has defined conditions so that yields as high as 86 % can be obtained at room temperature. The preferred solvent is 5 % methanol in benzene, with boron trifluoride etherate as catalyst. With either methanol or benzene, the yield is less than 4%. 

One reaction touched upon briefly in an earlier discussion is the hydroxyla-tion of a A -20-cyano steroid with osmium tetroxide. When a 21-acetoxyl group is also present, the important dihydroxyacetone side-chain is obtained ... 

Epimerization of 4 at C-2 provided 5a-carba-a-DL-galactopyranose (6). When the pentaacetate IS was heated in acetic acid containing sulfuric acid, epimerization occurred at C-2 through an intermediary cyclic acetoxonium ion (18), with anchimeric assistance of the vicinal, axial acetoxyl group. After acetylation, 5a-carba-a-DL-galactopyranose pentaacetate (19) was obtained in a yield of 14% it was converted into 6 by hydrolysis. The antimicrobial activity of the racemate 6 was found to be about half that of the natural antibiotic 7 in the same assay system, indicating that the L-antipode is probably inactive. " ... 

Structural variants in structure 11 appear compatible with high-affin-ity binding to antithrombin. Thus, the acetoxyl group of residue ANA6S could be removed (by hydrazinolysis) and replaced by a sulfate group without loss of affinity.172 Natural, high-affinity oligosaccharides con-... 

P2j Z = 2 Dx = 1.363 R = 0.051 for 982 intensities. The lactone has the3T4 conformation, withQ = 13 pm, (p = 337°, andaC-2-C-3-C-4-O torsion-angle of — 120. Both the equatorial and the axial acetoxyl groups have their planes approximately normal to that of the lactone ring. 

Hydroxyprotoberberine 59a and ( )-corytencine (98) led to 13-acetoxy compounds 104,105, and 107 moreover, the 2,3,9,10,12-pentaoxy-genated protoberberine 108 was also obtained from 98 via the p-quinol acetate 106 through a retro-Mannich reaction followed by recyclization (74,75). Oxidation in dichloromethane instead of acetic acid proceeded differently, namely, 97 and 98 led to pentaoxygenated protoberberines 103 and 109 by introduction of an acetoxyl group at C-4 and C-12, respectively, via o-quinol acetates (76). 

Support for the above view comes from NMR studies of the binding of phenyl and nitrophenyl acetates to a-CD (Komiyama and Hirai, 1980). These indicate that the nitro groups are located in the CD cavity and that the acetoxyl groups of the esters are held outside, more or less close to the secondary hydroxyls of the CD. It was calculated that the distance between the ester carbonyl carbon and the secondary hydroxyls decreases as p-nitro > phenyl > m-nitrophenyl, consistent with the observed order of rate acceleration (Komiyama and Bender, 1984). 

The intermediate products, which are represented within brackets, are exceptionally labile since they contain OH and the negative acetoxyl group attached to the same carbon atom (cf. p. 103) they therefore decompose into two molecules of acid or, in the case of ammonia, into acetic acid and acetamide. The reaction with alcohols is to be formulated in the same way. It will be observed that, when an acyl group is introduced (into an alcohol, amine, etc.) by means of an anhydride, one of the two acid radicles in the molecule is always converted into the acid and is consequently not used in the acylation. The great reactivity of the acid chlorides has the same cause as that discussed in connexion with the anhydrides. 

Interestingly, the acetoxyl group in the product comes not from acetic acid (a solvent) but from acetate ion (a conducting electrolyte)—salts with tosylate or perchlorate anions stop acetoxylation in the solution of acetic acid. 

The second necessary fragment, 7-amino-3-(l-pyridinomethyl)cef-3-en-carbonic acid (32.1.2.80), is synthesized from cefalosporidin (32.1.2.79), a cephalosporin antibiotic that is used independently in medicine and which is synthesized in the form of an internal salt by reacting cefalotin (32.1.2.1) with pyridine to replace the acetoxyl group with a pyridine group. Initially treating cephaloridin with trimethylchlorosilane in the presence of dimethylaniline and then with phosphorous pentachloride, followed by a reaction with 1,... 

Another limonoid isolated from neem seeds and determined to be as potent as azadirachtin as an ecdysis inhibitor has been identified as 3-deacetylazadirachtinol (Figure 15) (57). Both compounds were lethal to 50% of the treated H. virescens larvae (EI5Q) at 0.8 ppm in artificial diet (Table VII). Structurally, there are two differences between the compounds. In 3-deacetylazadirachtinol, the C-ll-O-C-13 ether linkage of azadirachtin is reductively cleaved at the 11 position and the acetoxyl group at C-3 is hydrolyzed to a hydroxyl group. 

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