1,3-acyl shift

Recently, the use of Hpase enzymes to iateresterify oils has been described (23). In principle, if a 1,3-speciftc Hpase is used, the fatty acid ia the 2 position should remain unchanged and the randomization occur at the terminal positions. However, higher temperatures, needed to melt soHd fats, may cause a 1,2-acyl shift and fatty acids are scrambled over all positions. 

In radical reactions not involving bromine or chlorine on the substrate, rearrangements are much rarer One example is the fluorination of di-tert butyl ketone which produces perfluormated / rt-buty isobutyl ketone [J5] Although isolated yields are poor only the rearranged ketone could be isolated This is perhaps only the second example of a 1,2-acyl shift Low fluorine substrate ratios show that this rearrangement occurs after monofluorination... 

As has been outlined for the Strecker synthesis, the Ugi reaction also proceeds via initial formation of a Schiff base from an aldehyde and an amine. The imine intermediate is attacked by the isocyanidc, a process which is supported by protonation of the imine by the carboxylic acid component. The resulting a-amino nitrilium intermediate is immediately trapped by the carboxylate to give an 6>-acyl imidiate. All steps up to this stage are reversible. Only the final oxygen to nitrogen acyl shift is irreversible and delivers the A-acyl-a-amino amide as the thermodynamically favored product which contains two amide groups. 

Photochemical changes in both II and the acetoxy derivative have been monitored in fluid solution and incorporated in a polymer film. Fig. 5 shows the spectral changes accompanying photochemical transformation of the acetoxy derivative. Then changes may be interpreted in terms of scheme 3, which proposes a photochemical 1,3 acyl shift to form "in situ" an ultraviolet stabilizer chromophore which also has a carbonyl functionality. 

As mentioned earlier (cf. chapter 2.1.1), p,y-enones undergo an 1,3 acyl shift from the Si-state. In sensitized reactions they rearrange to cyclopropyl ketones in the so termed oxadi-pi-methane rearrangement, as illustrated for... 

ACID-INDUCED O-ACYLATION OF SIDE-CHAIN HYDROXYLS AND THE O-TO-N ACYL SHIFT... 

The popular acids for deprotection by acidolysis are hydrogen fluoride for benzyl-based protectors and trifluoroacetic acid for rerr-butyl-based protectors. The use of hydrogen fluoride for deprotection emerged from the observation that it is a good solvent for dissolving enzymes (because of the N-to-0 acyl shift see Section 6.6), and that the enzymatic activity is recovered (O-to-N acyl shift) in saline solution. Two different approaches are employed for removal of benzyl-based... 

Fig. 1.3 The currently accepted chemical mechanism of protein splicing. 1 N-S(O) acyl shift, 2 transesterification, 3 cleavage by succinimide formation, 4 S(0)-N acyl shift.

It is noteworthy that there is another limiting factor in the choice of amino acid types at the junction sites which affect the enzymatic process of the intein. For example, in the case of SceVMA (also called PI-Seel) from the IMPACT system, proline, cysteine, asparagine, aspartic acid, and arginine cannot be at the C-terminus of the N-terminal target protein just before the intein sequence. The presence of these residues at this position would either slow down the N-S acyl shift dramatically or lead to immediate hydrolysis of the product from the N-S acyl shift [66]. The compatibility of amino acid types at the proximal sites depends on the specific inteins and needs to be carefully considered during the design of the required expression vectors. The specific amino acid requirements at a particular splicing site depends on the specific intein used and is thus a crucial point in this approach. 

In line with the above-mentioned reactivity of cysteine thioesters is the occurrence of a S, N-acyl shift of the palmitoyl group from the thiol side chain to the a-amino group, when this amino group is present as a free amine. 

A study of the absolute rate constants for [1,2]-H and [l,2]-acyl shifts in a series of alkylacetoxycarbenes (93), generated by photolysis of the corresponding diazirines, showed that an a-methyl group is ca 12 times more effective at promoting [1,2]-H shift than an a-Ph group. ... 

The reaction of diazoazoles and isocyanates leading to azolo-tetra-zinones of type 258 (Scheme 75) can be regarded as a [7 -l- 2]cycloaddition of the diazoazoles to the electron-deficient hetero double-bond of the isocyanates (pathway a) or, alternatively, as a two-step reaction involving [3 -I- 2]cycloaddition of the diazoazoles to the isocyanates, leading to the spirostructure 259 and subsequent [l,5]acyl shift (pathway b). An additional two-step mechanism (pathway c) could involve nucleophilic attack by the azole ring nitrogen on the carbonyl isocyanate to give a zwitterionic intermediate that collapses to the [7 + 2]cycloadduct 258. 

Photoisomerization of the unsaturated lactone (200) to the 1,5-cyclo-lactone (201) provides the first example of a Type A rearrangement in an j8-unsaturated lactone. An X-ray structure analysis has confirmed the photoisomerization of the /3-y-unsaturated ketone (202) to the cyclopentanone (203) by a 1,3-acyl shift. A similar rearrangement of the 3-oxo-A "° " -compound (204) to the cyclo-butanone (205) is in contrast with earlier reports of the oxo-di- r-methane rearrangement of 3-oxo-A " Lcompounds on direct irradiation. Benzophenone-... 

The 3//-l,2,4-diazaphospholes formed from the reaction of diazomethane and its monosubstituted derivatives (R CH=N2 R = H, alkyl, aryl, acyl, phosphoryl) could not be isolated due to a rapid 1,5-H shift leading to 27/-l,2,4-diazaphospholes 227. When diazo(trimethylsilyl)methane or [bis(diisopropylamino)phosphino]dia-zomethane was used, the l,5-SiMe3 [or PR2, R = N(/-Pr)2] shift completely dominates over the H shift (289,290). In the case of open-chain or cyclic a-diazoketones, cycloadducts 228 cannot be isolated due to rapid acyl shifts giving 229 and ultimately 230 (289). This transformation offers a versatile method to prepare [h]-fused 1,2,4-diazaphospholes from cyclic a-diazoketones and phos-phaalkynes (289). 

To prevent the S—>N acyl shift, S-palmitoylation with palmitoyl chloride is performed in anhydrous solvents on N -aminoacylated cysteines, e.g. dipeptide building blocks, whereby the residual functionalities of the peptide have to be protected taking into account the base-lability of the thioester bond. 

Due to the S—N acyl shift, the stepwise synthesis using a S-palmitoylated cysteine derivative is not advisable. A more convenient approach is to assemble the peptide sequence and to acylate the cysteine thiol group upon its selective deprotection, retaining, however, the protection of other reactive groups. For this purpose the Cys(StBu) and Cys(Acm) deriv-... 

Conversion of Cyclic Peptides into Cyclic Depsipeptides by N—>0 Acyl Shift... 

Peptides containing serine or threonine may undergo an N—>0 acyl shift upon exposure to strong acids (Scheme 40). 592,594 This reaction has been exploited in the structure elucidation of cyclosporin A, since the acid-catalyzed acyl shift with formation of an ester allowed its selective hydrolysis to the linear peptide for further stepwise degradation. 593 ... 

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