Hydrazones are the basis ofbioconjugation strategies.[8][9] Hydrazone-based coupling methods are used in medical biotechnology to couple drugs to targeted antibodies (seeADC), e.g. antibodies against a certain type of cancer cell. The hydrazone-based bond is stable at neutral pH (in the blood), but is rapidly destroyed in the acidic environment oflysosomes of the cell. The drug is thereby released in the cell, where it exerts its function.[10]
InN,N-dialkylhydrazones[17] the C=N bond can be hydrolysed, oxidised and reduced, the N–N bond can be reduced to the free amine. The carbon atom of the C=N bond can react with organometallic nucleophiles. The alpha-hydrogen atom is more acidic by 10orders of magnitude compared to the ketone and therefore more nucleophilic. Deprotonation with for instancelithium diisopropylamide (LDA) gives anazaenolate which can be alkylated by alkyl halides.[18] The hydrazines SAMP and RAMP function aschiral auxiliary.[19][20]
Recovery of carbonyl compounds from N,N-dialkylhydrazones
Several methods are known to recover carbonyl compounds from N,N-dialkylhydrazones.[21] Procedures include oxidative, hydrolytic or reductive cleavage conditions and can be compatible with a wide range of functional groups.
^Christie, R.; Hill, J.; Rosair, G. (2006). "The crystal structure of CI Pigment Yellow 97, a superior performance Hansa yellow pigment".Dyes and Pigments.71 (3):194–198.doi:10.1016/j.dyepig.2005.07.001.
^Algar, W. Russ; Prasuhn, Duane E.; Stewart, Michael H.; Jennings, Travis L.; Blanco-Canosa, Juan B.; Dawson, Philip E.; Medintz, Igor L. (2011). "The Controlled Display of Biomolecules on Nanoparticles: A Challenge Suited to Bioorthogonal Chemistry".Bioconjugate Chemistry.22 (5):825–858.doi:10.1021/bc200065z.PMID21585205.
^Wu, Anna M.; Senter, Peter D. (7 September 2005). "Arming antibodies: prospects and challenges for immunoconjugates".Nature Biotechnology.23 (9):1137–46.doi:10.1038/nbt1141.PMID16151407.S2CID27226728.
^Outirite, Moha; Lebrini, Mounim; Lagrenée, Michel; Bentiss, Fouad (2008). "New one step synthesis of 3,5-disubstituted pyrazoles under microwave irradiation and classical heating".Journal of Heterocyclic Chemistry.45 (2):503–505.doi:10.1002/jhet.5570450231.
^Lazny, R.; Nodzewska, A. (2010). "N,N-dialkylhydrazones in organic synthesis. From simple N,N-dimethylhydrazones to supported chiral auxiliaries".Chemical Reviews.110 (3):1386–1434.doi:10.1021/cr900067y.PMID20000672.
^Enders, Dieter; Reinhold, Ulrich (1997). "Asymmetric synthesis of amines by nucleophilic 1,2-addition of organometallic reagents to the CN-double bond".Tetrahedron: Asymmetry.8 (12):1895–1946.doi:10.1016/S0957-4166(97)00208-5.
^Enders, Dieter; Fey, Peter; Kipphardt, Helmut (1987). "(S)-(−)-1-Amino-2-methoxymethylpyrrolidine (SAMP) and (R)-(+)-1-amino-2-methoxymethylpyrrolidine (RAMP), Versatile Chiral Auxiliaries".Organic Syntheses.65: 173.doi:10.15227/orgsyn.065.0173.S2CID260330996.
^Enders, Dieter; Kipphardt, Helmut; Fey, Peter (1987). "Asymmetric Syntheses Using the SAMP-/RAMP-Hydrazone Method: (S)-(+)-4-methyl-3-heptanone".Organic Syntheses.65: 183.doi:10.15227/orgsyn.065.0183.
![X-ray structure of DNP-derived hydrazone of benzophenone. Selected parameters: C=N, 128 pm; N-N, 138 pm, N-N-C(Ar), 119 pm[22]](/mt/?noimg=&dark=on&url=https%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aNERYOZ.png)
