Novel Amination and 1,2-Amino,hydro-Elimination between 2,3-Diketopyrido[4,3,2-de]quinolines and Primary Amino Compounds

1999-09-30T00:00:00Z (GMT) by Qizhu Ding J. William Lown
A novel amination and 1,2-amino,hydro-elimination reaction occurs between 2,3-diketopyrido[4,3,2-de]quinoline (1, 2) and amino compounds which include α-amino acids and peptides which contain a primary amino group. The amino group undergoes nucleophilic addition to the double bond between C3a and C4 in 2,3-diketopyrido[4,3,2-de]quinoline to form a 3a,4-dihydro-2,3-diketopyrido[4,3,2-de]quinoline. This dihydro intermediate is immediately oxidized by ambient air to produce the more stable aromatic system, 4-(N-alkyl or aryl)-2,3-diketopyrido[4,3,2-de]quinoline (512). In the cases of aliphatic amines bearing a β-proton in THF or chloroform, this 4-(N-alkyl)-2,3-diketopyrido[4,3,2-de]quinoline undergoes a 1,2-amino,hydro-elimination reaction to eliminate an alkene and produce the 4-amino-2,3-diketopyrido[4,3,2-de]quinoline (13, 14). In the cases of α-amino acids in aqueous solution, the 4-(N-alkyl)-2,3-diketopyrido[4,3,2-de]quinoline undergoes an amino-transferring reaction, via a mechanism similar to the action of pyridoxal, to form the 4-amino-2,3-diketopyrido[4,3,2-de]quinoline (13) and the α-keto acid. 2,3-Diketopyrido[4,3,2-de]quinoline (1) can also react with the peptide which contains a primary amino group to form the 2,3-diketopyrido[4,3,2-de]quinoline−peptide conjugate. This novel amination−elimination reaction may underlie the marked cytotoxic potency of the 2,3-diketopyrido[4,3,2-de]quinolines (1 and 2). As inorganic amino compounds, hydroxylamine and hydrazine can also undergo the nucleophilic addition to 2,3-diketopyrido[4,3,2-de]quinoline (1, 2) to produce 4-amino-2,3-diketopyrido[4,3,2-de]quinoline (13, 14) which includes a elimination reaction between C4 and α-nitrogen.