Cleavage with hydroxylamine

In the cases investigated, the label could be removed by prolonged incubation of the labeled enzyme with 0.5 M hydroxylamine at pH 9.4 and 36°. With )8-glucosidase from almonds, it was necessary to denature the enzyme with guanidinium chloride before complete cleavage with hydroxylamine was possible. This stability of the label in the native, or only partially denatured, enzyme stands in marked contrast to the lability observed with labeled peptides obtained from these enzymes (see below). 

Diphenylthiirene 1-oxide reacts with hydroxylamine to give the oxime of benzyl phenyl ketone (79JA390). The reaction probably occurs by addition to the carbon-carbon double bond followed by loss of sulfur monoxide (Scheme 80). Dimethylamine adds to the double bond of 2,3-diphenylthiirene 1,1-dioxide with loss of sulfur dioxide (Scheme 81) (75JOC3189). Azide ion gives seven products, one of which involves cleavage of the carbon-carbon bond of an intermediate cycloadduct (Scheme 81) (80JOC2604). 

Hydroxamic acids are an important class of compounds targeted as potential therapeutic agents. A-Fmoc-aminooxy-2-chlorotrityl polystyrene resin 61 allowed the synthesis and subsequent cleavage under mild conditions of both peptidyl and small molecule hydroxamic acids (Fig. 14) [70]. An alternative hydroxylamine linkage 62 was prepared from trityl chloride resin and tV-hydroxyphthalimide followed by treatment with hydrazine at room temperature (Scheme 30) [71]. A series of hydroxamic acids were prepared by the addition of substituted succinic anhydrides to the resin followed by coupling with a variety of amines, and cleavage with HCOOH-THF(l 3). 

Another mechanism of nitroxyl radical regeneration was proposed and discussed in the literature [67-71]. The alkoxyamine AmOR is thermally unstable. At elevated temperatures it dissociates with cleavage of the R—O bond, which leads to the appearance of an [AmO + R ] radical pair in the cage of polymer. The disproportionation of this radical pair gives hydroxylamine and alkene. The peroxyl radical reacts rapidly with hydroxylamine thus... 

Condensation of aromatic or aliphatic esters with resin-supported acetyl carboxylic acids 28 followed by cyclisation with hydroxylamine, activation of the linker, and cleavage using amines, provided highly substituted isoxazoles 30 and 31. This general method gave products in excellent yields and purities in which the regioisomers ratio can be easily controlled . 

The reductive cleavage of hydroxylamine and its derivatives by electro-generated TP and V forming aminyl radicals and the hydroxide ions has been studied intensively. The aminyl radicals are preferably trapped with alkenes and aromatic compounds. Thus, the reaction of hydroxylamine with electro-generated Tp in the presence of maleic acid yields aspartic acid (Eqs. (66)—(69))... 

The linkage Asp-Gly can often be cleaved specifically by treatment with hydroxylamine at high pH.195 Procedures for specific cleavage of tryptophanyl bonds have been de-... 

Hydroxamic acids and hydrazides can also be prepared by nucleophilic cleavage of resin-bound esters, activated amides, or thiol esters [359] with hydroxylamine and... 

Strategies that lead to the formation of isoxazoles during cleavage from an insoluble support include the oxidative cleavage of /V-(4-alkoxybenzyl)isoxazolidincs with DDQ to yield isoxazolines (Entry 14, Table 15.16), the nucleophilic cleavage of 2-acyl enamines with hydroxylamine (Entry 15, Table 15.16), and the acidolysis of 2-cyano-phenols etherified with an oxime resin (Entry 17, Table 15.16). The required oxime ethers for the latter synthesis were prepared by reaction of the corresponding 2-fluorobenzonitriles with Kaiser oxime resin [203],... 

A preparatively satisfactory means of selective enol ester cleavage consists in the treatment with hydroxylamine, which not only induces hydroxylaminolysis of the more reactive enol ester group to form the respective hydroxamic acid, but captures the keto group thus liberated in the form of its stable oxime (29) ... 

A great deal is known about the photochemistry of carbenes (Chapter 2) and in the cases of the diazirine precursors given here (Table 3.1) it can confidently be predicted that the adducts formed on irradiation with proteins will be stable under most of the conditions necessary for further study (Fig. 2.1). Of course common sense should be exercized, e.g. insertion into carboxyl groups will yield esters which are unstable to hydrolysis or to treatment with hydroxylamine (e.g. Ross et al., 1982), and the possibility of reaction with peptide bonds culminating in polypeptide chain cleavage has already been mentioned (Section 2.1, Fig. 2.2). 

No reactions of either 1,2-dithiolium salts or trithionium salts with hydroxylamine have been described in the literature. The explanation in the case of the trithionium salts is probably the fact that the expected condensation products, i.e., the oximes of the Baumann-Fromm disulfides, can be obtained via the trithiones themselves2 this is one of the few examples in which trithiones react with carbonyl reagents without undergoing cleavage of the 1,2-dithiole ring. 

---