N -► O acyl rearrangement

Fig. 2. Schematic diagram of the catalytic mechanism of 20S proteasomes. A proton transfer from the hydroxyl group of Thrl of /3 subunits to its own terminal amino group initiates the nucleophilic attack (I). As a result of the nucleophilic addition to the carbonyl carbon of the scissile peptide bond, a tetrahedral intermediate is formed (II). By an N—O acyl rearrangement, an ester is formed (the acyl enzyme) and the amino-terminal cleavage product is released (III). Finally, hydrolysis of the acyl enzyme yields the carboxyl-terminal cleavage product and frees the enzyme for another reaction cycle (IV).

Reported examples of isomerization of drag substances include trans-cis isomerization of amphotericin B (Scheme 33),148 N,O-acyl rearrangement of cyclosporin A (Scheme 34),149 and dienone-phenolrearrangement of steroids such as tirilazad (Scheme 35).150... 

Application of N O Acyl Rearrangement Reaction to Clupeine Z, Followed by Selective Chemical Cleavage of the Chain, Leading to the... 

The N O acyl rearrangement reaction at the hydroxyamino-acid residues (Ser and Thr) and the selective chemical cleavage of the chain at the resulting ester bonds have been studied in detail using unfractionated clupeine (Iwai, 1959, 1960, 1961 Iwai and Ando, 1967). This method of degradation retains intact sequences of arginine residues in the products. 

Chart VIII-3. N O Acyl rearrangement reaction of dupeine Z followed by selective chemical degradation (Ando f/ at/., 1962 Iwai et aL 1971)... 

It is concluded on the basis of the chemical structure determined for the protamine that the N — O acyl rearrangement reaction of clupeine Z and the selective chemical degradation proceed as shown in Chart VIII-3. 

Chart VIII-4. The amino-acid sequence of clupeine YII with demonstration of amino acids obtained by terminal analyses, and peptides by tryptic hydrolysis and selective chemical hydrolysis after N -> O acyl rearrangement reaction [Ando and Suzuki, 1966 Suzuki and... 

When clupeine or salmine is treated with concentrated sulfuric acid, N —> O acyl rearrangement takes place at the N-terminal peptide bonds involving serine and threonine residues in a yield of about 70% (Iwai, 1959). In order to achieve selective... 

Iwai, K., Nakahara, C., Ando, T. Studies on protamine. XV. The complete amino acid sequence of the Z component of clupeine. Application of N -> O acyl rearrangement and selective hydrolysis in sequence determination. J. Biochem. (Tokyo) 69, 493—509 (1971). Jaques, L. B. a study of the toxicity of the protamine, salmine. Brit. J. Pharmacol. 4, 135—144 (1949). 

The second major metabolite from T. inflation is structurally closely related to cyclosporin A, as can be deduced by elemental analysis, mass spectrum (m/z 1217), IR and NMR spectra. Furthermore, the presence of the double bond and OH group of the unusual MeBmt was established. Sulphonic acids in methanol or dioxane effected the typical rearrangement reaction by N, O-acyl migration to the iso-compound (13). Hydrolysis furnished the same amino acids as cyclosporin A with the exception of L-a-aminobutyric acid, which is replaced in cyclosporin C (12) by L-threonine. The amino-acid sequence could be deduced by conversion of cyclosporin C into cyclosporin A via the corresponding tosylate (14) and iodo derivatives (15) [7]. Position 2 for L-threonine as well as the assumed twisted -pleated sheet conformation of the molecule were confirmed by 13C-NMR spectra. 

The acyl azide - isocyanate rearrangement is known to proceed stereospecifically with retention of both optical and geometrical (cis-tranSy endo-exo) configuration. Thus, optically active aminocyclopropanes were obtained from optically active cyclopropane carboxylic acid derivatives A lot of exo-amiobicyclo[n.l.O]alkanes or... 

The resolving agent must now be removed by hydrolysis of the amide. This is a risky business as enolisation would destroy the newly formed stereogenic centre, and a cunning method was devised to rearrange the amide 30 into a more easily hydrolysed ester by acyl transfer from N to O. The rest of the synthesis is as before. By this means the alcohol 28 was obtained almost optically pure, <0.4% of the other enantiomer being present. No further reactions occur at the newly formed stereogenic centre, so the absolute chirality of 22 is as shown. 

Huisgen and co-workers studied the kinetics of the Beckmann rearrangement of O-acylated benzocycloalkane oximes (107) [n = 2-5 R = S02Ph,... 

In boiling xylene, 0-aryl 0-methyl O-2-propynyl phosphorothioates isomerize to 0-aryl 0-methyl 5-propadienyl phosphorothioates, although with only low to moderate conversions. The anions from the conventionally-synthesized mono-thiophosphate esters (76) (R = H or Ph, = H R R = (CH2)n, n = 3 or 4) rearrange, and on subsequent alkylation or acylation (R = Me, Et, Pr, Pr , Ac, Bu CO, (PhO)2P(X), X = O, S, or Se) yield the products (77) in the (Z) configuration the latter esters undergo Diels-Alder reactions with common dienophiles (e.g. acrylonitrile, acrolein, maleic anhydride, etc.) to give the systems... 

The phosphorothioic triamide (79) (R = H) exhibits ambident reactivity and when alkylated yields the pentacoordinated 5-derivatives (80), but when acylated affords (79) (R = PhCO or EtCO). The N io O rearrangement of the N-phosphorylated amino acid esters (81) to (82) proceeds 10-40 times faster in the presence of imidazole than in its absence. In a warm alcohol solution ester... 

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