Carbonyl hydrazide

A set of aryl halides was reacted with carbonyl hydrazides and molybdenum hexacar-bonyl [Mo(CO)6] as a source of carbon monoxide, employing fluorous triphenylphos-phine (F-TPP) as ligand and the perfluorocarbon liquid FC-84 as a perfluorinated solvent (Scheme 7.87 see also Scheme 6.46c). 

A protected serine hydrazide was condensed by the azide method to an S-protected tripeptide H-Asn-Cys-Tyr-NHNH-Cbz to form a protected tetrapeptide Boc-Ser-Asn-Cys-Tyr-NHNH-Cbz 1.02 g of N-rerr-butoxycarbonylserine hydrazide (Boc-Ser-NH-NHj) >n DMF containing HCI in dioxane was mixed at -20 °C with reri-butyl nitrite. This mixture containing the azide Boc-Ser-Nj was neutralized with triethylamine, and a solution of 3.4 g asparaginyl-S-(ethylcarbamoyl)cysteinyl-tyrosinyl 2-(benzyloxy-carbonyl)hydrazide trifluoroacetate was added. After 72 hours at 4 °C a simple work-up procedure and precipitation from methanol-petroleum ether yielded 3 g of impure protected retrapeptide hydrazide. It... 

Benzolphosphonsaure- (1,2-his- [ethoxy-carbonyl]-hydrazid)-methylester 77% Schmp. 108-110°... 

Heterocyclic compounds. DCC and carbonyl hydrazide in equimolar amounts react in refluxing DMF to give 4-cyclohexyl-3-cyclohexylamine-l,2,4-triazoline-5-one (1) in 45-50% yield. The reaction of carbonyl hydrazide (1 equivalent) and DCC (3 equivalents) in DMSO at 100° also yields (1), but the predominant product is 4-cyclohexyl-3,5-biscyclohexylamino-l,2,4-triazole (2). The reaction is applicable to other carbodiimides.4... 

Zamecnik and Stephenson (81) carried the approach previously used by Berg and co-workers (cf. 194) one step further by separating the non-esterified, periodate-treated RNA chains from the amino acid-bearing one, which is not attacked. For this purpose the dialdehyde resulting from periodate action was converted into an RNA carbonyl-hydrazide compound, thereby acquiring a rich, bluish-purple color it could then be separated from dye-free RNA by fractional precipitation with n-propanol, or by countercurrent distribution. VaUne-acceptor RNA of a high specific activity was isolated by this method. 

The Michael-type addition of maleic hydrazide and other pyridazinones to activated alkenes, such as methyl acrylate, acrylonitrile, methyl vinyl ketone and other a,/3-unsatu-rated carbonyl compounds, results in the formation of mono-lV-substituted products. 

L-alanylglycyl-L-cysteinyl-L-lysyl-L-asparaginyl-L-phenylalanyl-L-phenylalanyl-L-tryptophanyl-L-lysyl-L-threonyl-L-threonyl-L-cysteine 6-0-benzoyl-N-(benzyloxycarbonyl) methylamide 4,6-0-benzylidene-N-benzylidene-N-(benzyloxycarbonyl) methylamide N- (benzyloxy carbonyl) -N-(benzyloxycarbonyl)-, amide N-(benzyloxycarbonyl)-, hydrazide N-(benzyloxycarbonyl)-, methylamide N-(benzyloxycarbonyl)-, methyl ester N-(benzyloxycarbonyl)-L-alanyl-L-alanine methyl ester N-(benzyloxycarbonyl)-L-alanylglycine ethyl ester N-(benzyloxycarbonyl)glycyl-L-alanine methyl ester 3,4,6-tri-0-acetyl-2-amino-2-deoxy-N-(benzyloxycarbonyl)-, benzyl ester, hydrochloride... 

The formation of compounds 2-503 proceeds via the addition of a hydrazide 2-500 onto the central carbon of an isothiocyanate 2-499. Subsequent cyclization by attack of the hydrazide nitrogen in the formed 2-501 onto the nitrile moiety gives intermediate 2-502. A further attack of the newly formed amidine nitrogen onto the carbonyl group followed by extrusion of water affords the triazoloquinolines 2-503. 

Figure 1.70 AMBH is a hydrazide-containing compound that reacts with carbonyl groups to form hydrazone bonds. The free thiol can be used for subsequent conjugation reactions.

Hydrazide-containing compounds also can be coupled to carboxylate groups using a carbodiimide-mediated reaction. Using bifunctional hydrazide reagents, carboxylates can be modified to possess terminal hydrazide groups able to conjugate with other carbonyl compounds (Chapter 4, Section 8). 

The carbonyl-reactive group on these crosslinkers is a hydrazide that can form hydrazone bonds with aldehyde residues. To utilize this functional group with carbohydrate-containing molecules, the sugars first must be mildly oxidized to contain aldehyde groups by treatment with sodium periodate. Oxidation with this compound will cleave adjacent carbon-carbon bonds which possess hydroxyl groups, as are abundant in polysaccharide molecules (Chapter 1, Sections 2 and 4.4). 

Figure 5.12 MPBH reacts with sulfhydryl-containing molecules through its maleimide end to produce thioether linkages. Its hydrazide group then can be used to conjugate with carbonyl-containing molecules (such as periodate-oxidized carbohydrates that contain aldehydes) to give hydrazone bonds.

Perhaps a better design for a bis-hydrazide compound to modify carboxylate particles would include a short PEG spacer arm between the two hydrazide groups. This type of linker would result in a hydrophilic surface due to the presence of the PEG spacers, while providing the terminal hydrazide functionality necessary for coupling to carbonyl compounds. Unfortunately, this type of compound is not currently available, so the aliphatic bis-hydrazides are the only choice. 

Another route to the formation of a hydrazide on a surface is to use an aldehyde-containing particle (such as HEMA/acrolein copolymers) and subsequently modify the aldehydes to form hydrazone linkages with bis-hydrazide compounds, which then can be stabilized by reduction with sodium cyanoborohydride (Chapter 2, Section 5). The resulting derivative contains terminal hydrazides for immobilization of carbonyl ligands (see Figure 14.18). 

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