Migration 1.3 -acyl

Acylated Corticoids. The corticoid side-chain of (30) was converted iato the cycHc ortho ester (96) by reaction with a lower alkyl ortho ester RC(OR )2 iu benzene solution ia the presence of i ra-toluenesulfonic acid (88). Acid hydrolysis of the product at room temperature led to the formation of the 17-monoesters (97) ia nearly quantitative yield. The 17-monoesters (97) underwent acyl migration to the 21-monoesters (98) on careful heating with. In this way, prednisolone 17a,21-methylorthovalerate was converted quantitatively iato prednisolone 17-valerate, which is a very active antiinflammatory agent (89). The iatermediate ortho esters also are active. Thus, 17a,21-(l -methoxy)-pentyhdenedioxy-l,4-pregnadiene-liP-ol-3,20-dione [(96), R = CH3, R = C Hg] is at least 70 times more potent than prednisolone (89). The above conversions... 

Rearrangement involving cleavage of the C—O bond is also observed with the phenyl isocyanate adduct (59). In place of an O-acylated nitrone its product (60) of acyl migration is isolated (67JPR(36)86). 

CUSO4 (anhydrous), benzene, heat, 89-100% yield. In highly acylated carbohydrates, trityl removal proceeds without acyl migration. 

Two disadvantages are associated with the use of S-acetyl or 5-benzoyl derivatives in peptide syntheses (a) base-catalyzed hydrolysis of 5-acetyl- and 5-benzoylcys-teine occurs with /S-elimination to give olefinic side products, CH2=C-(NHPG)CO—(b) the yields of peptides formed by coupling an unprotected amino group in an 5-acylcysteine are low because of prior S-N acyl migration. ... 

Na/NH3, -30°, 3 min, 1(X)% yield. This protective group is stable to acidic hydrolysis (4.5 N HBr/HOAc 1 N HCV, CF3CO2H, reflux). There is no evidence of S N acyl migration in 5-(A-ethylcarbamates) (RS = cysteinyl). Oxidation of 5-(A-ethylcarbamoyl)cysteine with performic acid yields cysteic acid. ... 

Analogous acyl migrations occur with dienol acetates of type (238) and (239), yielding products from the two possible recombinations—(240)/(241) and (243)/(244), respectively—besides the products of reductive acetyl elimination (see Experiment b below). 

Isobutylene, H2S04. Acyl migration has been observed using these conditions. ... 

K2CO3, MeOH, H2O, 20°, 1 h, 100% yield. When catalytic NaOMe is used as the base in methanol, the method is referred to as the Zemplen de-O-acetylation. Acetyl groups are known to migrate under these conditions, but a recent study indicated that acyl migration is reduced with decreasing solvent polarity (6 1 chloroform/MeOH vs. MeOH)."... 

Interestingly, the first report of a reaction of this type was reported by Fischer and Rudolph earlier the same year Friedlander reported his quinoline synthesis.Heating of acetylaniline (7) in the presence of zinc chloride promotes acyl migration to furnish 2-aminoacetophenone (8) and 4-aminoacetophenone (9). These two molecules combine to furnish flavanilin (10). ... 

In contrast to the reaction of the betaine 58 in wet diethylether, wet THF, in which the betaine is better soluble, gives the methyl isoanhydroberberilate 64 in 71% yield. The mechanism seemingly involves an unusual carbon to nitrogen acyl migration as shown in Scheme 23. Hydration and air oxidation of the betaine to the peroxide leads to the formation of an aziridine intermediate and loss of a hydroxide anion (77TL3787). 

Infrared spectral evidence indicates that indazol 3-one probably exists in the oxo form (cf. 77). 4-Monosubstituted-l,3-diphenylpyrazol-5-ones have been assigned an oxo structure (cf. 78) on the basis of infrared (presence of a v C=N band) and ultraviolet spectral data. The structure of certain iV-acylated pyrazolones has been discussed on the basis of their infrared spectra, but in these cases the possibility of acyl migration is a complicating factor. 

Drefahl and Horhold discussed the mechanism of N 0 acyl migration in A -benzoyl-l,2-diphenyl-3-aminopropanols. The migration does not seem to be possible in the erythro isomer as it would give an intermediate tetrahydro-1,3-oxazine with a bulky phenyl group in axial position. Consequently the erythro isomer is cyclized with inversion to form 2,5,6-triphenyl-5,6-dihydro-l,3-4 -oxazine... 

Incorporation of extensive branching in the side chain similarly does not decrease pharmacologic activity. Reductive alkylation of aminoalcohol, 42, with isobutyraldehyde affords the amine, 43. Acylation of the amine with benzoyl chloride probably goes initially to the amide (44). The acid catalysis used in the reaction leads to an N to 0 acyl migration to afford iso-bucaine (45). ... 

In an analogous sequence, reductive alkylation of aminoalcohol, 46, with cyclohexanone affords the secondary amine (47). Acylation with benzoyl chloride affords hexylcaine (48) in a reaction that may again involve acyl migration. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Also the impact of various reaction parameters on enzymatic synthesis of amide surfactants from ethanolamine and diethanolamine has been studied, although the possibilities of acyl migration are not investigated. However, it was found that the selectivity of the reaction depended on the solubility of the product in the solvent used, and that the choice of solvent was critical to obtain an efficient process [17]. 

The Merck compound MK-0608 is a 2 -C-Me-7-deaza-adenosine analog, which has recently been reported to show a 5.7 log drop in viral load in HCV-infected chimpanzees after dosing QD at 2mg/kg (Olsen 2006). An efQcient and practical process for preparing kilogram quantities has been described (Bio et al. 2004). The 12-step synthesis provides an impressive 35% overall yield and starts from the inexpensive diacetone-D-glucose. The synthesis features a novel acyl migration in route to prepare the key crystalline furanose diol intermediate (Fig. 5). The conditions... 

No products arising from a nucleophilic reaction at C-2 were observed. The reaction with acetic acid also takes place regioselectively at C-3, but the initially formed anfz-3-acetoxy product undergoes an acyl migration to give the anti-3-hydroxy-2-acetamino product (see Scheme 21). 

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