Amides cleavage

The effects of cyclodextrins on this reaction, while potentially of great interest, have been rarely studied, presumably because amide hydrolysis is generally slow and so tedious to study. As a result, only two examples are considered here. 

Tutt and Schwartz (1971) studied the basic cleavage of some penicillin derivatives [31]— [32] in the presence of /3-CD. For acyl groups bearing alkyl and aryl substituents of various sizes and geometries, the accelerations ( c/ u) vary less (31-89) than the spread of Ks values (3.85-75 mM) (Table A5.16). Approximately, therefore, the XTS values vary in parallel with Ks, suggesting that the acyl group is involved in substrate and transition state binding to about the same extent. 

The basic hydrolysis of p-nitroacetanilide is retarded by a-CD, whereas that of trifluoroacetanilide and its m-nitro derivative is modestly enhanced 

The CD-mediated cleavage of p-N02C6H4NHC0CF3 proceeds by acyl transfer to a-CD. Since the trifluoracetyl-CD, so produced, hydrolyses fairly quickly even at pFI7, the overall reaction shows true catalysis. Thus, for the reaction in (27), a-CD behaves as a model enzyme and shows three of the features of chymotrypsin (i) it provides a hydrophobic binding site (ii) it catalyses the loss of leaving group and (iii) the reaction proceeds through an acyl intermediate (Komiyama and Bender, 1977 Bender and Komiyama, 1978). 

The anions of CDs may also function as simple basic catalysts towards acidic substrates included in their cavities. Such was observed by Daffe and Fastrez (1983) who studied the deprotonation and hydrolysis of oxazolones in basic media containing CDs. Also, in a paper dealing mainly with catalysis by amylose, it was noted that CDs catalyse the deprotonation of long chain /3-keto esters in basic aqueous DMSO (Cheng et al., 1985) no saturation kinetics were found for CDs, indicating weak substrate binding under the conditions used. 

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The great reactivity of the sulfurane prepared by this procedure toward active hydrogen compounds, coupled with an indefinite shelf life in the absence of moisture, makes this compound a useful reagent for dehydrations,amide cleavage reactions, epoxide formation, sulfilimine syntheses, and certain oxidations and coupling reactions. 

Amide Cleavage Induced by Nitro Group Reduction... 

For most common amides cleavage is quite difficult, but in the case of an aziridine (which exhibited reduced participation significantly in amide resonance because of the nonplanar amide moiety ) hydrolysis is much simpler, as shown in the following illustration ... 

As for other 1,4-diheterocines the cycloreversion ofsyn-bis-cr-homobenzene systems constitutes an easy access also to 1,4-oxazocines from appropriate precursors. At approximately 60 C, the arylsulfonamides 3 readily and quantitatively rearrange to the 4//-1,4-oxazocines 4, which can be used for the preparation of other derivatives via the corresponding anion 6 (M = K) formed on reductive amide cleavage.12... 

P(0)(0Me)H and [TpAr Me]Zn0P(0)(0R)2, respectively (Scheme 26) (35). In addition, [TpAr Me]ZnOH also cleaves activated esters and amides in a stoichiometric fashion, as illustrated in Scheme 27. Kitajima has described a similar amide cleavage reaction between the copper and nickel hydroxide complexes [Tp JMtOH) (M = Ni, Cu) and p-nitroacetanilide to give [TpPr 2]M p2-MeC(0)NC6H4N02 [Eq. (34)] (198). 

The structural elements that determine amide cleavage in compounds of type 4.139 were investigated in mouse liver homogenates [84] and can be summarized as follows Increasing the size of the /V-substitucnt (the R"" and R "" groups) increased the rate of hydrolysis, whereas it was decreased by the presence of substituents surrounding the amide bond (R to R "). The R" and R " groups were critical, and reactivity was considerably reduced for R"=Me and R "=H. Compounds substituted in both positions (R" = R " = Me) were resistant to amidase. 

A. V. Klotz, B. A. Thomas, W5-Methylasparagine and Asparagine as Nucleophiles in Peptides Main-Chain vs. Side-Chain Amide Cleavage , J. Org. Chem. 1993, 58, 6985-6989. 

The alkaline hydrolysis of the l,4-benzodiazepin-2-one (236) and its 4-oxide resulted in ring opening via amide cleavage. Similarly treatment with methylamine gave (246) which proved to be a useful intermediate in the synthesis of the 3-carboxamide (247). 

The findings that, both in ester and amide cleavage, an alkaline-earth metal ion is still catalytically active when complexed with a crown ether, and that a fraction of the binding energy made available by coordinative interactions with the polyether chain can be translated into catalysis, provide the basis for the construction of supramolecular catalysts capable of esterase and amidase activity. 

Cacciapaglia, R., Di Stefano, S., Kelderman, E. and Mandolini, L. (1999) Supramolecular catalysis of ester and amide cleavage by a dinuclear barium(II) complex. Angew. Chem., Int. Ed., 38, 348. 

A selective amide cleavage of proline-tethered azetidin-2-one 329 with sodium methoxide followed by cyclization of the resulting /3-amino ester resulted into formation of the ring-expanded indolizidine derivative 330 (Equation 115) <2005JOC8890>. 

In the proposed mechanism of hydrolysis (16), the carboxylate anion of 13-15 or acetyl Phe is recognized by the guanidinium ion, and the Cu(n) center subsequently hydrolyzes the amide group. Both the electrostatic interaction between carboxylate and guanidinium ions and the Cu(n)-catalyzed amide cleavage would be facilitated by the microenvironment provided by polystyrene. 

In the case of long-chain primary amides cleavage of the bond y to carbonyl can also take place, giving minor peaksat mass 72 (without rearrangement) and 73 (with rearrangement). 

Proline Tertiary amide Na in NH, Preferential amide cleavage So far not tested Hofmann (1960a), (Cleavage in special model compounds)... 

Hydroxyproline Tertiary amide 7-hydroxyl Na in NHa solvolytic agents Preferential amide cleavage Displacement of 0-Ts 7-lactone formation So far not tested So far not possible... 

Reference Molarity of NH2OH pH Reaction time (hr) Temperature (°C) Material Peptide cleavage Amide cleavage... 

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