Untitled

Hydroxamic Acids: Chemistry, Bioactivity, and Solutionand Solid‐Phase Synthesis

“…They release hydroxamic acids upon treatment with 1% or 95% TFA in DCM, respectively [155,182]. The use of 95% TFA and 5% water as a cleavage cocktail can be associated with substantial hydrolysis to the corresponding carboxylic acid [155].…”

“…The resulting hydroxylamine resin (45) gives a negative Kaiser test [150] and a positive ninhydrin test [153]. The resin substitution can be quantified by measuring phthaldrazide (46) absorbance at 346 nm [155] or evaluating the elemental analysis of the resin [150]. Loading of the carboxylic acid substrate for monomeric molecules and peptide mimetics, or of the first amino acid and elongation of the sequence in the case of peptide hydroxamic acids, is carried out by carbodiimide [154,156] or uranium [150,157] coupling chemistries, and by standard Fmoc chemistry [150], respectively.…”

Polymer-Supported N-Derivatized, O-Linked Hydroxylamine for Concurrent Solid-Phase Synthesis of Diverse N-Alkyl and N−H Hydroxamates

“…1 The most common preparative route to O-immobilized hydroxylamine is by the reaction of N-hydroxyphthalimide with Wang or Sasrin resins under Mitsunobu conditions. [2][3][4] Alternatively, hydroxyl resins can be converted to mesylate resins and reacted with N-hydroxyphthalimide, 5 or trityl chloride resins can be directly reacted with either N-hydroxyphthalimide [6][7][8] or N-Fmoc hydroxylamine. 9 The resulting polymer-supported hydroxylamines can then be elaborated through acylation with carboxylic acids to give various hydroxamic acids.…”

Product Class 5: Hydroxylamines

“…[506] O-tert-Butylhydroxylamine hydrochloride (340), a useful O-protected hydroxylamine, [507][508][509][510] is prepared in 85% yield by reaction of N-hydroxyphthalimide (317) with tert-butyl acetate and perchloric acid via tert-butoxyphthalimide (339), followed by hydrazinolysis and acidification with hydrochloric acid (Scheme 127). [507] Scheme 127 Synthesis of O-tert-Butylhydroxylamine Hydrochloride [507,511] O-Tritylhydroxylamine, which can also serve as an O-protected hydroxylamine, [512] is synthesized in 73% yield from trityl chloride and N-hydroxyphthalimide by hydrazinolysis of the intermediate N-(trityloxy)phthalimide. [513] Synthesis of the polymer-bound O-tritylhy-droxylamine 341 is realized in quantitative yield by reaction of chlorotrityl-derivatized Synphase crowns and N-hydroxyphthalimide, followed by subsequent deprotection.…”

“…[513] Synthesis of the polymer-bound O-tritylhy-droxylamine 341 is realized in quantitative yield by reaction of chlorotrityl-derivatized Synphase crowns and N-hydroxyphthalimide, followed by subsequent deprotection. [511] Reaction of N-hydroxyphthalimide, triethylamine, and 9-chloroxanthene in acetonitrile at room temperature, followed by cleavage of the intermediate N-(xanthen-9yloxy)phthalimide (342) with 40% aqueous methylamine, provides O-(xanthen-9-yl)hydroxylamine (343) in 45% yield as a crystalline compound (Scheme 128). [514] Analogously, O-(9-phenylxanthen-9-yl)hydroxylamine is obtained in 35% yield.…”