Cyanide‐Catalyzed Conjugate Addition of Aryl Aldehydes: 4‐oxo‐4‐(3‐Pyridyl)Butyronitrile

Stetter, Hermann; Kuhlmann, Heinrich; Lorenz, G.

doi:10.1002/0471264180.os059.09

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“…This approach took advantage of the commercially available nicotine aldehyde, which already contains the carbonyl function of the hapten. Condensing nicotine aldehyde 1 with acrylonitrile according to Stetter's procedure (25) gave the nitrile intermediate 2, whose carbonyl function was subsequently protected by a 1,3-dioxolane group through treatment with ethylene glycol in boiling toluene. Once the carbonyl was safely masked, the nitrile was catalytically reduced with H 2 /Raney-nickel as described by Soyka et al (26).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 4-[2-Aminoethyl(nitrosamino)]-1-pyridin-3-yl-butan-1-one, a New NNK Hapten for the Induction of N-Nitrosamine-Specific Antibodies

Prodhomme¹,

Ensch²,

Bouche³

et al. 2007

Bioconjugate Chem.

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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most abundant and potent procarcinogens in tobacco smoke. In order to induce a strong and substained antibody response against NNK, we developed a functionalized derivative that closely mimicked its structural features, in particular, the pyridyloxobutyl moiety, the adjacent ketone, and the N-nitrosamino group. This hapten was conjugated via a C 2 linker to the highly immunogenic diphteria toxoid licensed as a vaccine in humans to induce polyclonal and monoclonal antibodies. Two monoclonal antibodies were obtained with Kd values of 45.8 nM (P9D5) and 37.6 nM (P7H3), respectively, for NNK-C 2. Both the monoclonal (P9D5 and P7H3) and polyclonal antibodies reacted strongly with NNK (IC 50 = 80 microM or 160 microM) and NNAL (IC 50 = 29 microM or 93 microM) and to a lesser extent with some of the metabolites of NNK. Interestingly, the mAbs did not react with the metabolites of the detoxification pathways such as NNK-N-Oxide and NNAL-N-Oxide (IC 50 > 512 microM). Therefore, such antibodies detect NNK and NNAL and may have the potential to modulate their redistribution in vivo, perhaps reducing some detrimental effects of smoking.

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Section: Resultsmentioning

confidence: 99%

Synthesis of 4-[2-Aminoethyl(nitrosamino)]-1-pyridin-3-yl-butan-1-one, a New NNK Hapten for the Induction of N-Nitrosamine-Specific Antibodies

Prodhomme¹,

Ensch²,

Bouche³

et al. 2007

Bioconjugate Chem.

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Cyanide‐Catalyzed Conjugate Addition of Aryl Aldehydes: 4‐oxo‐4‐(3‐Pyridyl)Butyronitrile

Abstract: Cyanide‐Catalyzed Conjugate Addition of Aryl Aldehydes: 4‐OXO‐4‐(3‐PYRIDYL)BUTYRONITRILE reactant: 107.1 g. (1.001 mole) of 3‐pyridinecarboxaldehyde product: 4‐oxo‐4‐(3‐pyridyl)butyronitrile product: R1 = C 6 H 5 , R2 = R3 = H … Show more

Cited by 1 publication

References 13 publications

Synthesis of 4-[2-Aminoethyl(nitrosamino)]-1-pyridin-3-yl-butan-1-one, a New NNK Hapten for the Induction of N-Nitrosamine-Specific Antibodies

Synthesis of 4-[2-Aminoethyl(nitrosamino)]-1-pyridin-3-yl-butan-1-one, a New NNK Hapten for the Induction of N-Nitrosamine-Specific Antibodies

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