Hydroxamic acids ureas

AT-Alkyl Urea Hydroxamic Acids as PDF Inhibitors with Antibacterial Activity... 

Scheme 22 Synthesis of N-alkyl urea hydroxamic acids as PDF inhibitors...

Hydroxy- urea Hydroxamic acid if HjN NH 1 OH OH H H202/CuZn-S0D or ceruloplasimin, H202/Cu2+, heme-containing proteins Peroxidase Guanylate cyclase... 

Finally, the Lessen rearrangement provides a practical procedure for replacing the hydroxamic group of a hydroxamic acid (12) by an amino group (14) (equation 2). The initial rearrangement product is an isocyanate (13) which readily reacts with nucleophiles, for example with OH and NH functionalities to give amines (14) and ureas (15). 

A partially purified enzyme from P. mirabilis (72) was found to have a molecular weight of 151,000. The urease of P. rettgeri is an inducible enzyme that appears only when urea, but not its analogs, are present in the media (73). Proteus vulgaris urease was found to be inhibited in vitro by thiourea and two derivatives (74), and by hydroxamic acids (93). 

Hackbarth, C.J. et al. 2002. V-alkyl urea hydroxamic acids as a new class of peptide deformylase inhibitors with antibacterial activity. Antimicrob. Agents Chemother. 46, 2752-2764. 

Rearrangement of O-acyl hydroxamc acxl derivatives with base or heat to amines or urea derivatives (via Isocyanates) or rearrangement of cartioxylic acids via their hydroxamic acids to amines... 

Amides and ureas The sulfonamides undergo functional group exchange on reaction with thiolacetic acid, hydroxamic acids, and R2NC(=S)SH, in the presence of cesium carbonate. Reaction of the sulfonamides with dithioacids affords thioamides. 

This reaction was first reported by Lossen in 1872. It is a thermal or alkaline conversion of hydroxamic acid into an isocyanate via the intermediacy of its O-acyl, sulfonyl, or phosphoryl derivative. In the presence of water, amine, or alcohol, the isocyanate is converted into amine, urea or urethane, respectively. Therefore, this reaction is generally known as the Lossen rearrangement. Occasionally, it is also referred to as the Lossen reaction, Lossen degradation, or Lossen transformation. ... 

Ureas from hydroxamic acids and isocyanates GONHOH NHGONHR... 

In a sequence involving a Lessen rearrangement, the treatment of 7V,7V disubstituted 2,4-dinitrophenylsulfonamides (4) with hydroxamic acid (14), and cesium carbonate in DMF led to the corresponding ureas (15) in 19% yield (eq 7). ... 

Hydroxamic acid 3 can be converted to activated hydroxamate 2 via reaction with a variety of electrophilic reagents. The Lossen rearrangement is then initiated by exposure of 2 to base or heat resulting in anion 10. Through a fast subsequent transformation via cyclic intermediate 12, isocyanate 1 is generated. This isocyanate 1 can be further converted to urea 13 or amine 15. 

Alternatively, the oxidation may occur by coupling to a suitable reactant. In 1997, Miyashita explored the scope of oxidative aroylations with nitrobenzene (Scheme ll.lO)." With the same oxidative reagent, nitrobenzene, benzoin reactions had already been developed back in 1982 using cyanide or thiamine. The combination of an aldehyde and nitrosobenzene, in the presence of an NHC, led to the formation of 7V-phenyl hydroxamic acids in good yields. These can be further converted into hydroxamic esters via a one pot reaction in the presence of a second (o,p-unsaturated) aldehyde. Furthermore, the oxidative coupling of aldehydes with carbodiimides in air allowed access to Af-acyl urea derivatives with IMes HCl 19 as the NHC precursor. Related thioesterifications reactions have also been reported using... 

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